Improvement In Hematological Parameters Research Articles

Effect of Supplementation of <i>Lepidium sativum</i> (Garden Cress Seed) Incorporated Chikkies on Tribal Anaemic Adolescent Girls (12-18 Years) in Nilgiris District

India has the highest prevalence of Iron Deficiency Anaemia (IDA), and 60-70 per cent of adolescent girls are being anaemic. Adolescence is considered as nutritionally critical period of life. The health of adolescent girls need special attention. To overcome this problem, food based approaches have been considered as the most acceptable, safe and sustainable approach. Keeping all these views in mind the present study was carried out. Ethical Approval for the study was obtained from the Universal Ethics Committee. Screening for Anaemia was done by assessing haemoglobin levels of 500 adolescent girls. From that 100 moderately anaemic adolescent girls (each 50 in experimental and control groups) were chosen for further study. The chikkies incorporated with Lepidium Sativum (Garden cress seeds) with other ingredients was supplemented to experimental group daily for a period of 3 months. Haematological parameters like HB, RBC, PCV, MCV, MCH was assessed both prior and after supplementation. Control group was given only plain chikkies without any incorporation. There was a significant improvement in haematological parameters like Hb, RBC, PCV, MCV, MCH in experimental group and there was no significant change in control group. It shows that incorporation of Lepidium Sativum seeds in foods has goodhealth impact.

Hypolipidemic and cardioprotective effects of Ulva lactuca ethanolic extract in hypercholesterolemic mice

Context: Hypercholesterolemia has significant cardiac consequences, since it is among the major risk factors of ischemic heart diseases.Objective: The aim was searching the cardioprotective effect of chemical constituents from the sea lettuce Ulva lactuca upon hypercholesterolemic regime in mice.Material and methods: Mice were randomly divided into three groups: untreated group, hypercholesterolemic group, and mice receiving 1% cholesterol associated with U. lactuca ethanolic extract.Results: In vitro study demonstrated that algal extract has antioxidant efficacy attributable to the presence of phenolic compounds. Additionally, the alga alleviated cardiotoxicity, as shown by the improvement of haematological parameters, white cell viability, heart oxidative stress, plasma biochemical parameters and index of atherogenesis. Gene expression of the proinflammatory cytokines TNF-α, IL-1β and IL-6 significantly decreased in the heart of U. lactuca supplemented hypercholesterolemic animals.Conclusion: It was established that the green alga, thanks to its bioactive compounds, effectively counteracts cardiotoxic effects of hypercholesterolemic regime.

Safety and efficacy of intravenous iron polymaltose, iron sucrose and ferric carboxymaltose in pregnancy: A systematic review.

Intravenous (IV) iron in pregnancy is useful where oral iron is not tolerated or a rapid replenishment of iron is required. To review the literature on the efficacy and safety of different IV iron preparations in the management of antenatal iron-deficiency anaemia (IDA). We searched MEDLINE, Embase and Scopus from inception to June 2016. Eligible studies were randomised controlled trials (RCTs) and observational studies, involving administration of IV iron (ferric carboxymaltose (FCM), iron polymaltose (IPM) or iron sucrose (IS)), regardless of comparator, to manage antenatal IDA. Two independent reviewers selected studies, extracted data and assessed quality. A total of 47 studies were eligible (21 RCTs and 26 observational studies), investigating IS (n=2635; 41 studies), FCM (n=276; four studies) and IPM (n=164; three studies). All IV preparations resulted in significant improvements in haematological parameters, with a median increase of 21.8g/L at 3-4weeks and 30.1g/L by delivery, but there was no evidence of any associated improvements in clinical outcomes. A greater median increase in Hb was observed with a high (25g/L; range: 20-39.6g/L) compared with low dose (20g/L; range: 6.2-50.3g/L). The median prevalence of adverse drug reactions for IPM (2.2%; range: 0-4.5%) was lower than FCM (5.0%; range: 0-20%) and IS (6.7%; range: 0-19.5%). While IV iron in pregnancy improves haematological parameters, there is an absence of evidence for improvements in important maternal or perinatal outcomes. No single preparation of IV iron appeared to be superior, with the current IV iron preparation of choice largely determined by cost and convenience around administration.

Hydroxyurea prescription, availability and use for children with sickle cell disease in Italy: Results of a National Multicenter survey.

The number of patients with sickle cell disease (SCD) has increased in Italy in the past decade due to immigration. In spite of the established efficacy of hydroxyurea (HU) in childhood, population-based data regarding its prescription and effectiveness come mainly from studies performed in adults or outside Europe. The Hydroxyurea in SCD: A Large Nation-wide Cohort Study from Italy was a retrospective cohort study of adult and pediatric patients with SCD attending 32 centers. Pediatric data are analyzed separately. Out of 504 children followed in 11 centers, 206 (40%) were on HU (194 SS/Sβ°, 12 SC/Sß+); 74% came from Sub-Saharian Africa and 18% from Europe. HU therapy indications for SS/Sβ° patients were as follows: 57% painful vaso-occlusive crisis, acute chest syndrome or both, 24% anemia, 8% anemia, and other reasons (the majority had Hb ≤ 8-8.5g/dl, revealing scarce acceptance of low Hb values by pediatric hematologist). Mean starting dose was 15.5mg/kg, and dose at full regimen was 17.1mg/kg. Mean age at HU therapy was 7.68 years, although it was lower for SS/Sβ° patients. Only 10% started HU before 3 years. In 92%, 500mg capsule was used; in 6%, the galenic was used; and in 2%, 100mg tablet was used. Significant reduction of clinical events and inpatients admissions, with improvement in hematological parameters, was observed for SS/Sβ° patients and a trend toward improvement for SC/Sß+ patients was also observed. HU effectiveness is demonstrated in a national cohort of children with SCD living in Italy, even at a lower dose than recommended, revealing good adherence to a treatment program by a socially vulnerable group of patients such as immigrants.

Variable Penetrance Is Linked with Monoallelic Gene Expression in Inherited GATA2-Mutated MDS/AML

Background: While myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are considered sporadic hematopoietic stem cell clonal disorders, there are rare occurrences of familial cases (<5%) where two or more individuals within the same family are affected. These high-risk examples are characterised by wide variations in the age of onset, disease latency and outcome between and within families, making their investigation, follow-up and treatment all the more challenging.To date, germline mutations in 11 disease genes have been described, with mutations in the myeloid transcription factor GATA2 representing one of the best-characterised genetic loci predisposing to inherited hematological malignancies. We have noted that within GATA2 families, particularly those segregating a germline p.Thr354Met mutation, there is striking evidence of reduced penetrance. In our example, two first-degree cousins (III.1 and III.3) developed high-risk MDS with monosomy 7 with a third cousin (III.7) presenting with significant leukopenia (monocytopenia [0.1x109/L] and neutropenia [0.8x109/L]). This contrasts with the parental generation (II.1, II.3 and II.5) who all remain hematologically normal and symptom free into their mid-late 60s (Figure 1). We therefore set out to understand these differences in clinical presentation between mutation carriers.Aims:To investigate the molecular mechanisms underlying the variable penetrance and clinical heterogeneity observed in a GATA2-mutated family.Results:Targeted deep-sequencing of 33 genes frequently mutated in MDS/AML revealed a low overall burden of acquired mutations in the symptomatic carriers with no mutations detected in asymptomatic family members. It was noteworthy that an acquired ASXL1 mutation (p.Gly646TrpfsTer12) was identical in all affected individuals (III.1, III.3 and III.7) (Figure 1) although the variant allele frequency was lower (12%) in III.7 and remained stable (range 12-6%) over a 4 year monitoring period. GATA2 expression was lower in III.7 as assessed by quantitative RT-PCR and strikingly this was associated with monoallelic expression of the mutated GATA2 allele with complete loss of the wild-type (WT) allele expression. Temporal analysis of III.7 at yearly intervals demonstrated reactivation of the WT allele 2 years later, coinciding with a marked improvement in hematological parameters (normal monocyte count, neutrophils >1x109/L). These changes in GATA2 expression were not linked to gross changes in methylation, as assessed by methylation specific PCR and bisulphite sequencing, nor acquisition of additional mutations in the WT promoter. Instead, we believe that allele-specific fluctuations in expression are accompanied by changes in chromatin structure at the promoter. Using a SNP (rs1806462 [C/A]) located in the 5’UTR of GATA2, we assessed allele-specific enrichment of H3K4me3 and H3K27me3 chromatin marks by chromatin immunoprecipitation. Sanger sequencing revealed a significant enhancement in the deposition of H3K4me3 activating chromatin mark on the mutated allele compared to the WT allele at diagnosis and this was reversed at later follow-up, correlating with reactivation of the WT allele expression. There were no discernible allele-specific differences in the H3K27me3 mark across the phenotypes at different time-points.Conclusion: Variable penetrance amongst germline mutation carriers is a feature of many families with inherited forms of MDS/AML and this may be related to the nature of secondary genetic events acquired in at-risk individuals. In this study, however, we show that changes in the WT:mutant allele expression ratio as a result of local and allele-specific changes in chromatin deposition may also influence the penetrance of the inherited mutation. [Display omitted] DisclosuresCavenagh:Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau.

Preliminary Results from a Phase I Dose Escalation Trial of Ruxolitinib and the PI3Kδ Inhibitor TGR-1202 in Myelofibrosis

Background: Therapies for myelofibrosis (MF) are limited and most are palliative. The JAK1/2 inhibitor ruxolitinib reduces spleen size and MF-related symptoms and improves survival, but can be limited by dose-dependent anemia and thrombocytopenia. Moreover, nearly half of ruxolitinib responders relapse within 5 years. PI3Kd is highly expressed in MF patient samples, independent of ruxolitinib pre-exposure. In JAK2-mutated cell lines, inhibition of PI3K/AKT signaling reduced proliferation and clonogenic potential. The once daily, next generation PI3Kd inhibitor TGR-1202 inhibited PI3K/AKT signaling and led to apoptosis in leukemia and lymphoma cell lines and was well-tolerated in clinical studies, with a toxicity profile distinct from that of ruxolitinib and other PI3Kd inhibitors. We hypothesized that adding TGR-1202 to ruxolitinib could resensitize or augment the response of MF patients with lost or suboptimal response to single-agent ruxolitinib.Objective: To assess safety of TGR-1202 in combination with ruxolitinib in MF patientsSecondary Objectives: Hematologic response, symptom assessmentMethods: MF patients who had sub-optimal responses to ruxolitinib continued their highest tolerated dose of ruxolitinib without change for ≥ 8 weeks, and were assigned to escalating doses of TGR-1202 in a standard 3+3 algorithm. Adverse events (AEs) were graded by NCI-CTCAE v4.03. Efficacy was assessed according to IWG-MRT consensus response criteria. Symptoms were assessed by the MPN symptom assessment form total symptom score (TSS). All patients received Pneumocystis pneumonia prophylaxis after cycle 1.Results: Eleven MF patients were enrolled and received 400 mg (n=3), 800 mg (n=6), or 600 mg TGR-1202 (n=2) daily. Nine were evaluable for response. Median age was 66y, 73% were male. All had ECOG PS 0-1. Five patients had mutations in JAK2, 4 in CALR, and 3 in MPL; these were mutually exclusive with exception of 1 patient with CALR and MPL mutations (Table 1). Median number of cycles of TGR-1202 + ruxolitinib treatment was 5 (1-13). Grade 2 anemia was the most common AE (Table 2). Two patients had asymptomatic Grade 3 elevations in amylase and lipase that persisted after drug was held, meeting criteria for dose limiting toxicities (DLTs) in 2 separate cohorts (TGR-1202 800mg+ruxolitinib 15mg BID and TGR-1202 800mg+ruxolitinib 10mg BID). Both patients had peak plasma TGR-1202 concentrations 1.5-2x higher than the other patients receiving 800mg TGR-1202, although steady-state levels were equivalent. The maximum tolerated dose (MTD) of TGR-1202 in combination with ruxolitinib was not established. Two patients went off-study due to AEs, and 3 due to progressive disease. One of 9 evaluable patients achieved complete remission and 7 had stable disease. Seven of the 9 evaluable patients had improvement in hematologic parameters and 8 had reduced MF symptoms with a median 33% decrease in TSS (Fig. 1).Conclusions: TGR-1202 + ruxolitinib was well-tolerated. Pharmacokinetic data were consistent with single-agent TGR-1202 (unpublished data), indicating that ruxolitinib does not alter absorption or metabolism of TGR-1202. Grade 3 elevations in amylase and lipase were considered DLTs, per protocol. Although the clinical significance of these asymptomatic laboratory findings is not clear, the protocol was amended to further assay these labs and to exclude concomitant medications with the potential to increase amylase/lipase. Importantly, no grade ≥3 hepatotoxicity, colitis, or thrombocytopenia was seen and no MTD was found. Although only one patient achieved CR, 89% demonstrated clinical benefit with the addition of TGR-1202 to ruxolitinib, supporting further exploration of this combination. [Display omitted] DisclosuresStrickland:Alexion Pharmaceuticals: Consultancy; Ambit: Consultancy; Baxalta: Consultancy; Boehringer Ingelheim: Consultancy, Research Funding; CTI Biopharma: Consultancy; Daiichi Sankyo: Consultancy; Sunesis Pharmaceuticals: Consultancy, Research Funding; Abbvie: Research Funding; Astellas Pharma: Research Funding; Celator: Research Funding; Cyclacel: Research Funding; GlaxoSmithKline: Research Funding; Karyopharm Therapeutica: Research Funding; Sanofi: Research Funding. Miskin:TG Therapeutics, Inc: Employment, Equity Ownership. Cavers:TG Therapeutics: Employment, Equity Ownership. Sportelli:TG Therapeutics, Inc.: Employment, Equity Ownership. Michaelis:Pfizer: Equity Ownership; Cellgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte Corporation: Consultancy, Honoraria. Mesa:CTI: Research Funding; Promedior: Research Funding; Celgene: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Galena: Consultancy; Ariad: Consultancy; Novartis: Consultancy. Savona:Amgen Inc.: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Research Funding; Ariad: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Sunesis: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees.

A study of yoga in anemic patients

Background: Anemia is a clinical condition characterized by reduction in number of red blood cells (RBCs) less than 4 million/mL or their content of hemoglobin less than 12 g/dL or both. Anemia is characterized by general malaise, lassitude, easy fatigability, weakness, tinnitus, exertion dyspnea, and poor concentration. It is a common condition prevalent in our society among men, women, children, and elderly people. The causes of anemia are variable ranging from acute blood loss to chronic blood loss, dietary deficiency, and dyshemopoietic, immune, and hemolytic disorders. Women and children are more prone to anemia. Yoga is a self-discipline method of integrating the body, breath, and mind and attaining one’s full potential. The antistress and antioxidant effect of yoga is beneficial in the improvement of hemotological parameters in anemic patients. Yoga increases the circulation of blood and improves the functioning of the entire circulatory system. Objective: To assess the effect of yoga on the hematological parameters among anemic patients. Materials and Methods: This study was conducted on 100 anemic subjects, with 50 men and 50 women, aged between 25 and 40 years. The various hematological parameters studied were hemoglobin, RBC, white blood cell (WBC), and platelet count. Result: The data were analyzed using unpaired t test. The study revealed significant increase in hemoglobin (p < 0.0001) and RBC (p < 0.0001) in both men and women. The WBC count significantly decreased in both men (p < 0.0001) and women (p < 0.0001). The mean value of platelet count increased in both men and women but was statistically insignificant in men (p = 0.3798) and women (p = 0.3479). Conclusion: Yoga is a cheap and cost-effective discipline that can be added to the drug therapy for improvement in hematological parameters in anemic patients.

A Phase 2 Study to Evaluate the Efficacy and Safety of Simtuzumab in Adult Subjects with Primary, Post Polycythemia Vera (PV) or Post Essential Thrombocythemia (ET) Myelofibrosis

Background: Simtuzumab (SIM) is a humanized monoclonal antibody that inhibits lysyl oxidase-like molecule 2 (LOXL2), an extracellular matrix enzyme that catalyzes the covalent cross-linking of collagen and is widely expressed across many fibrotic diseases. In pre-clinical models, inhibition of LOXL2 blocks fibroblast activation, which plays an important role in the development of organ fibrosis. In Phase 1 studies, SIM was well-tolerated in patients (pts) with advanced solid tumors, liver fibrosis, and idiopathic pulmonary fibrosis (IPF). A Phase 2, open-label study to determine the efficacy of SIM alone (Stage 1) and combined with ruxolitinib (rux) (Stage 2) in pts with primary myelofibrosis (PMF) and post-ET/PV MF was initiated.Methods: Eligible pts had intermediate-1, intermediate-2, or high risk disease and Eastern Cooperative Oncology Group performance status of <2. The primary endpoint was rate of clinical response as defined by a reduction in bone marrow fibrosis score following 24 weeks of treatment with SIM. Patients were randomized in a 1:1 ratio to receive 200 mg or 700 mg SIM by intravenous infusion every 2 weeks as monotherapy (Stage 1, n=24) or combined with rux (Stage 2, n=30). Patients received SIM for up to 24 weeks. Bone marrow biopsies and aspirates were performed approximately every 3 months. Bone marrow fibrosis scoring was performed and quantified at local investigator sites using the European Consensus on Grading Bone Marrow Fibrosis. Myelofibrosis symptoms were evaluated using the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and changes in hematologic parameters and splenomegaly were assessed.Results: Between 7/14/11 and 9/22/14, 54 pts were randomized and treated (200 mg SIM [n=12], 700 mg SIM [n=12], 200 mg SIM/rux [n=15], and 700 mg SIM/rux [n=15]). In Stage 1, 0 subjects (0%) in the SIM 200 mg group and 2 subjects (16.7%; 90% CI 3.0%, 43.8%) in the SIM 700 mg group showed a reduction in bone marrow fibrosis score from Baseline to Week 24. In Stage 2, 1 subject (6.7%; 90% CI 0.3%, 27.9%) in the SIM 200 mg/rux group and 2 subjects (13.3%, 90% CI 2.4%, 36.3%) in the SIM 700 mg/rux group showed a reduction in bone marrow fibrosis score from Baseline to Week 24. In an exploratory analysis, similar numbers of subjects showed increases in bone marrow fibrosis scores. SIM treatment was not associated with meaningful improvements in hematologic parameters or reductions in MPN-SAF score or spleen size. The most frequent adverse events were those commonly associated with MF, including constitutional symptoms and reductions in hematological parameters.Conclusions: SIM treatment alone or in combination with rux is safe but does not reliably reduce bone marrow fibrosis in pts with MF. The reason for reduction of marrow fibrosis in some patients and increase in others is unclear and may be sampling variability. Clinical studies of SIM in IPF and liver fibrosis are ongoing. DisclosuresSavona:Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Research Funding; Astex Pharmaceuticals, Inc: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Mesa:Incyte Corporation: Research Funding; CTI Biopharma: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Pfizer: Research Funding; Promedior: Research Funding; Genentech: Research Funding; NS Pharma: Research Funding; Gilead: Research Funding. Oh:CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Dong:Gilead Sciences: Consultancy, Equity Ownership. Thai:Gilead Sciences: Employment, Equity Ownership. Gotlib:Allakos, Inc.: Consultancy.

The effects of intermittent hypoxia training on hematological and aerobic performance in triathletes

The aim of the present research was to analyze modifications on hematological and aerobic performance parameters after a 7-week intermittent hypoxia training (IHT) program. Eighteen male trained triathletes were divided in two groups: an intermittent hypoxia training group (IHTG: n: 9; 26.0 ± 6.7 years; 173.3 ± 5.9 cm; 66.4 ± 5.9 kg; VO₂max: 59.5 ± 5.0 ml/kg/min) that conducted a normoxic training plus an IHT and a control group (CG: n: 9; 29.3 ± 6.8 years; 174.9 ± 4.6 cm; 59.7 ± 6.8 kg; VO₂max: 58.9 ± 4.5 ml/kg/min) that performed only a normoxic training. Training process was standardized across the two groups. The IHT program consisted of two 60-min sessions per week at intensities over the anaerobic threshold and atmospheric conditions between 14.5 and 15% FiO₂. Before and after the 7-week training, aerobic performance in an incremental running test and hematological parameters were analyzed. After this training program, the IHTG showed higher hemoglobin and erythrocytes (p < 0.05) values than in the CG. In terms of physiological and performance variables, between the two groups no changes were found. The addition of an IHT program to normoxic training caused an improvement in hematological parameters but aerobic performance and physiological variables compared to similar training under normoxic conditions did not increase.

Managing atypical hemolytic uremic syndrome: chapter 2

Licht et al. present the 2-year follow-up data of the landmark trials studying the efficacy of eculizumab in the treatment of atypical hemolytic uremic syndrome (aHUS). They report sustained improvements in hematologic parameters, continued safety, and additional improvements in kidney function with extended treatment. This report adds a layer of comfort to our care of patients with this rare disease; however, it is unlikely to be the final chapter in the treatment of aHUS.

Rutin potentially attenuates fluoride-induced oxidative stress-mediated cardiotoxicity, blood toxicity and dyslipidemia in rats

This study was undertaken to evaluate cardio protective effect of rutin against sodium fluoride (NaF)-induced oxidative stress-mediated cardiotoxicity and blood toxicity. Cardiac injury was induced by daily administration of NaF 600 ppm in distilled water for four weeks. The animals exposed to NaF exhibited a significant increase in levels of cardiac serum markers, lipid peroxidative markers, serum total cholesterol, LDL, triglycerides and decrease in HDL levels. Decrease in hematological parameters, namely hemoglobin, red blood cells, mean corpuscular volume, mean corpuscular hemoglobin (MCH), MCH count and increase in white blood cells and erythrocyte sedimentation levels were also observed. Marked histopathological lesions and increased DNA fragmentation in cardiac tissues were observed. Activity of antioxidants-catalase, superoxide dismutase and reduced glutathione contents were decreased (p < 0.01), whereas lipid peroxidation product (malondialdehyde) was increased. A significant decrease in body and heart weight was also observed. Treatment with rutin effectively ameliorated the alterations in the studied parameters of rat through its antioxidant nature. There was also significant improvement in hematological parameters. Thus, results of this study clearly demonstrated that treatment with rutin against NaF intoxication has a significant role in protecting F-induced cardiotoxicity, blood toxicity and dyslipidemia in rats.

Adaptive splenic radiotherapy for symptomatic splenomegaly management in myeloproliferative disorders.

Symptomatic, massive splenomegaly is a debilitating complication of myeloproliferative disorders. In the study, we evaluated the use of a contemporary, individualized radiotherapeutic approach for splenic irradiation, including 3-dimensional computed tomography-based treatment planning, individualized treatment margins based on splenic motion assessment, online setup verification with volumetric image guidance at each fraction, and adaptive radiation treatment planning to account for changes in splenic size during the fractionated radiotherapy course. Between December 2008 and January 2014, 18 patients (13 males, 5 females) with myeloproliferative disorders referred to Gulhane Military Medical Academy Radiation Oncology Department underwent 22 courses of splenic irradiation using 3-dimensional computed tomography-based treatment planning and volumetric image guidance for palliation of symptomatic splenomegaly. Median age was 64 years (range 28-79). Significant pain relief was achieved in 20 of the 22 splenic irradiation courses (90.9%). Improvement in hematological parameters was achieved in 8 of the 11 splenic irradiation courses applied for cytopenia (72.7%). At least a 50% reduction in splenic size was achieved in 18 of the 22 splenic irradiation courses (81.8%). Toxicity was manageable with supportive treatment including antiemetics and platelet or red blood cell transfusions. Splenic irradiation with a contemporary radiotherapeutic approach offers safe and effective palliation of symptomatic splenomegaly in myeloproliferative disorders.

Effects of a Year Long Wrestling Training Season on Biochemical Blood Parameters of Elite Wrestlers

The focus of this study is aimed at examining the effects of a year-long wrestling session on variation of hematological parameters of forty-two elite wrestlers. Biochemical parameters were studied during transition period of a year long wrestling season for each year. The findings of the study indicated that among the hematological variables studied, only RBC counts, MO, MCH, MCHC, and hematocrit had significant variations. According to the findings, MO, hematocrit, and RBC count increased significantly after one year of wrestling training while MCH and MCHC values decreased after one-year training. There were differences between pre and post-test results of SGOT, cholesterol, and urea variables. The study results indicated that more experience wrestling training had some positive effects on hematological parameters. The increase in red blood cells, and decrease cholesterol and urea values of the wrestlers after wrestling season are positive signs of improvements in hematological parameters of the wrestlers.

Mycophenolic Acid, Mycophenolate Mofetil, Mizoribine, Ribavirin, and 7-Nitroindole Inhibit Propagation ofBabesiaParasites by Targeting Inosine 5′-Monophosphate Dehydrogenase

The resistance of Babesia parasites to current anti-babesiosis drugs is an issue of major concern. The inosine 5'-monophosphate dehydrogenase (IMPDH) of Babesia gibsoni has been identified and characterized as a molecular drug target in our previous studies. In the present study, inhibitory effects of IMPDH inhibitors (mycophenolate mofetil, mizoribine, ribavirin, 7-nitroindole, and mycophenolic acid) were evaluated in vitro or in vivo. In the inhibition assay of recombinant B. gibsoni IMPDH activity, mycophenolate mofetil was the most potent inhibitor (IC(50) = 2.58 ± 1.32 μM) while ribavirin was the least potent. The inhibitory effects of mycophenolate mofetil, mizoribine, ribavirin, and 7-nitroindole on the in vitro growths of B. gibsoni and Babesia bovis were also assessed. The results revealed that mycophenolate mofetil was the most potent inhibitor of the multiplications of both B. gibsoni (IC(50) = 0.13 ± 0.05 μM) and B. bovis (IC(50) = 0.97 ± 0.49 μM). Ribavirin was also the least potent for both B. gibsoni and B. bovis in vitro. Mycophenolic acid, a metabolite of mycophenolate mofetil, caused an inhibition of Babesia microti in mice with noticeable improvement in hematological parameters of the infected mice (ED(50) = 44.15 ± 12.53 mg/kg). Although the report provides a non-exhaustive view of potential treatment strategy without addressing the potential adverse effect of immune suppression on infections, these results indicated that the IMPDH might be a molecular target of MPA for B. microti . Altogether, we provide a basis for development of antibabesia prodrugs by targeting IMPDH of the parasites in the treatment of babesiosis.

Effect of Probiotic Consortium on the Local Inflammatory Process in Chronic Periodontitis.

IntroductionInflammatory periodontal disease is one of the major concerns of researchers and clinicians, because it can lead to tooth loss and an increased risk of systemic pathologies, even at the age of 35. The purpose of this study was to determine the effects of gelatin-based probiotic consortium on the local and general factors of inflammation in rats with chronic periodontitis.MethodsThe study object was a complex of probiotic bacteria based in an odourless 6% gelatin plate with neutral flavour. A cellular biomass of the consortium consists of following lactobacilli: Lactobacillus casei subsp. pseudoplantarum, Lactobacillus caseisubsp.casei, L.fermentum, and L. helveticus. The viable cell number was 2.5 × 109 CFU/ml. The model of chronic periodontitis was reproduced in the white random-bred rats that weighed 160–220g, by keeping them on a low-protein diet. After three months, symptoms associated with medium and severe chronic periodontitis were observed in the rats. Application was carried out on the oral mucosa of rats 1 time per day for 14 days. The stickers lacking consortium of microorganisms were used as the placebo. The “Solcoseril” gel was chosen as a comparator. The hematologic, biochemical, and morphological characteristics were investigated.ResultsA complete clearance of periodontal pockets was observed during an objective examination of the experimental group rats on the 14th day of the experiment. Moreover, a gingival mucous turned pink, and there were no cyanosis tissues. The local changes were accompanied by improvement in hematological parameters, such as a reduction of blood eosinophilia and neutrophilia, and a recovery of the white blood cells number to the normal degree within the group that received the probiotic complex. A decrease of the acute plethora of microvasculature was observed morphologically as a result of the treatment. There were signs of basal layer activation of the stratified squamous epithelium with a merger of the acanthosis outgrowths and a formation of the fibrotic nodules. Biochemical investigations did not show significant changes in the indicators.ConclusionsIn the settings of the chronic periodontitis model, the use of gelatin-based probiotic consortium consisting of Lactobacillus casei subsp. pseudoplantarum, Lactobacillus caseisubsp.casei, L.fermentum, L. helveticus. at 2.5 × 109 CFU/ml viable cell numbers lead to the reduction of the local inflammatory manifestations of the periodontitis in 14 days of treatment.

Nephroprotective Effects of Carvedilol and Curcuma longa against Cisplatin-Induced Nephrotoxicity in Rats

Objective: Goal of this study is to investigate the effects of carvedilol (5 mg/kg, p.o), aqueous and methanolic extract of Curcuma longa (500mg/kg, p.o) against cisplatin induced renal damage in Wistar rats after a single intraperitoneal injection of 7.5mg- 1. Methods: Wistar rats were randomly divided into 7 groups (n=10). Rats in group I were normal control received normal saline (5 ml/kg; i. p.) on day zero, while group VIa and VIb were vehicle control, received carboxymethyl cellulose (2.5 ml/kg; p.o.) and propylene glycole (2.5 ml/kg, p.o.) respectively from day 3 to 17. Renal toxicity was induced in rats of group II, III, IV and V by a single administration of cisplatin (7.5 mg/kg; i. p.) on day zero. Rats in group III, IV and V received a daily dose of carvedilol (5 mg/kg; p.o.), aqueous and methanolic extracts of Curcuma longa (500 mg/kg; p.o.) respectively from day 3 to 17, while group II served as cisplatin control. Results: Post treated rats with carvedilol and aqueous and methanolic extracts of Curcuma longa for 15 days significantly increased body weight, decreased cisplatin induced abnormalities and mortality and decreased all the kidney marker such as serum urea nitrogen (SUN), serum creatinine (SCr), total proteins (TP), and uric acid (UA) increased by cisplatin, however, no appreciable improvement in hematological parameters were observed when compared with cisplatin control. Conclusion: The results are indicative of nephroprotective effects of carvedilol as well as aqueous and methanolic extracts of Curcuma longa. DOI: http://dx.doi.org/10.3126/ajms.v5i2.5483 Asian Journal of Medical Science, Volume-5(2) 2014: 91-98

Time To Hematologic and Renal Improvements In Atypical Hemolytic Uremic Syndrome Patients With Long Disease Duration and Chronic Kidney Disease (CKD) Treated With Eculizumab

IntroductionAtypical hemolytic uremic syndrome (aHUS) is a genetic, life-threatening, chronic, and progressive disease of thrombotic microangiopathy (TMA). Plasma exchange/plasma infusion (PE/PI) has been shown to lack efficacy in patients (pts) with aHUS. Despite PE/PI, up to 65% of pts sustain permanent renal damage, progress to end-stage renal disease, or die within 1 year (yr) of diagnosis. Among aHUS pts with long disease duration and CKD receiving chronic PE/PI, significant improvements in hematologic parameters and renal function were achieved in a clinical trial of eculizumab (Ecu). The current analysis was undertaken to gain better insight into the timing of hematologic and renal improvements in a 26-week (wk), Phase 2 trial with a long-term extension. MethodsaHUS pts ≥12 yrs of age with long disease duration and CKD receiving chronic PE/PI were enrolled. This analysis assessed the percentage of pts achieving each of the following outcomes – all for ≥2 consecutive measurements, ≥4 wks apart – at specific time points: Platelet count normalization (≥150x109/L); LDH ≤ULN; serum creatinine (Cr) decrease ≥25%; eGFR increase ≥15 mL/min/1.73 m2; and CKD improvement ≥1 Stage. Results20 pts aged ≥12 yrs receiving long-term PE/PI were enrolled and treated with Ecu in a 26-wk, single-arm, Phase 2 trial, and 19 continued in the extension study. The median time (range) from aHUS diagnosis to screening was 48.3 months (0.7–285.8), and the median time from the current manifestation of aHUS to screening was 8.6 months (1.2–45). The median duration of Ecu treatment at the time of the data cut was 114 wks. Mean baseline values were as follows: platelet – 228x109/L; Hb – 10.7 g/L; LDH – 223 U/L; Cr – 287 μmol/L; and eGFR – 30.8 mL/min/1.73 m2. 3 pts had platelet counts <150 x109/L at baseline, and 4 had LDH levels >ULN.The timing and duration of the criteria-defined hematologic and renal improvements during continued treatment with Ecu are shown in Figure 1. At wk 4, the percentage of pts achieving platelet and LDH normalization was 75% and 50%, respectively (the first assessable time point based on the criteria definition). 90% of pts had platelet count normalization by wk 8, which was sustained with ongoing Ecu treatment for the remainder of the study period. 85% of pts had LDH ≤ULN by wk 8, which increased to 95% by wk 12 (Figure 1). With ongoing Ecu treatment, 10% of pts achieved Cr decrease (≥25%) at wk 14, and 55% by wk 80. eGFR increase (≥15 mL/min/1.73 m2) was first seen at wk 18 (by 5% of pts). This proportion increased to a maximum of 40% at wk 104 with ongoing Ecu treatment. CKD improvement (≥1 Stage) was seen at wk 4 by 5% of pts. This proportion increased to 60% at wk 76 with ongoing Ecu treatment (Figure 1). Significant mean changes from baseline in eGFR were observed as early as wk 4, and were followed by time-dependent improvements through the end of the study (Figure 2). All patients were able to discontinue PE/PI. [Display omitted] [Display omitted] ConclusionsThe use of Ecu in aHUS pts with long disease duration and CKD on long-term PE/PI led to sustained normalization of hematologic values within the first month of treatment, followed by time-dependent improvements in renal function. These data demonstrate that improvement in renal function may be achieved over time in pts with long-standing aHUS and CKD, and underscore the importance of ongoing and consistent treatment with Ecu. The underlying mechanism of the observed renal function improvement over the study period (e.g., normalization of endothelial cell function) warrants further exploration. Disclosures:No relevant conflicts of interest to declare.

Production of Methioninase from &lt;i&gt;Serratia Marcescens&lt;/i&gt; Isolated from Soil and its Anti-Cancer Activity against Dalton’s Lymphoma Ascitic (DLA) and Ehrlich Ascitic Carcinoma (EAC) in Swiss Albino Mice

Purpose: To evaluate the anticancer activity of an enzyme, methioninase, obtained from a soil isolate, Serratia marcesens, against Dalton’s lymphoma ascitic (DLA) and Ehrlich ascitic carcinoma (EAC) in Swiss albino mice.Methods: Cancer was induced using DLA and EAC cells in Swiss albino mice by intraperitoneal injection. The mice were then treated with 10 and 20 mg/kg body weight of methioninase; 5-fluorouracil (5-FU) was used as standard.Results: The results showed good improvement in haematological parameters, improvement serum enzymes and lipid profile, as well as increase in life span by up to 77 %, increase in body weight (p &lt; 0.01), decrease in cancer cell count from (2.70 ± 0.40) × 106 to (1.86 ± 0.30) × 106 cells/ml compared to (2.70 ± 0.40) × 106 to (1.42 ± 0.25) x 106 cells/ml for the group treated with 5-FU. Solid tumor volume decreased from 5.82 ± 0.15 to 4.10 ± 0.11 ml as as against a decrease from 5.82 ± 0.40 to 3.56 ± 0.28 for the group treated with 5-FU.Conclusion: The isolated enzyme, methioninase, has a good anti-cancer activity and needs to be further be investigated for this activity.Keywords: Methioninase, Anticancer, Serum depletion, Tumor, Dalton’s lymphoma ascetic, Ehrlich ascitic carcinoma

Protective potential of Black grapes against lead induced oxidative stress in rats

From time immemorial Vitis vinifera (Black grapes) have been used both for medicinal and nourishment purposes. The aim of this study is to investigate the protective effect of Black grapes against lead nitrate induced oxidative stress. Exposure to lead significantly increased malondialdehyde levels with a significant decrease in superoxide dismutase and catalase activities, and the concentration of GSH in the liver and kidneys of rats. Significantly increased levels of AST, ALT, ALP, BUN and serum creatinine and decreased levels of total protein were observed. The administration of lead significantly decreased the body weight and organ weights at the end of the experimental period. Statistically significant decrease in hemoglobin, red blood cell and total leukocyte count was observed. Pretreatment of hydroalcoholic extract of Black grapes to lead exposed rats significantly ameliorated lead-induced oxidative stress in tissues and produced improvement in hematological parameters over lead-exposed rats, indicating the beneficial role of Black grapes to counteract the lead-induced oxidative stress.

Comparative study of efficacy and safety of Iron polymaltose complex with ferrous sulphate in antenatal women with moderate anemia

Iron deficiency is the most common cause of anemia in pregnancy. The conventional iron preparations with ferrous salts showed noncompliance due to various side effects when compared to iron polymaltose complex. But the efficacy of iron polymaltose complex (IPC) in the treatment of iron deficiency anaemia (IDA) during pregnancy has not been established, and the evidence is inconclusive. The aim of this study was to compare efficacy, safety, compliance and cost-effectiveness of ferrous sulphate (FS) with IPC in antenatal women. 100 antenatal women with 14 to 20 weeks of gestation were recruited in the study, one group of 50 women were given FS and the other group of 50 women were given IPC for 6 weeks. Haemoglobin concentration (Hb), Packed cell volume(PCV),Mean Corposcular Haemoglobin concentration and serum iron were estimated before and after treatment with the above iron formulations. Compliance with pill count and safety with adverse effects monitoring in followup were noted. Statistical analysis was done with student's T test and chi square test. The improvement of haematological parameters was comparable in both groups statistically but compliance and safety were better with the IPC group when compared to FS group. IPC is a better alternative to FS as it is safe and showed more compliance.