Commencement Of Induction Research Articles

Effects of Aqueous and Methanolic Extracts of Stem Bark of Alstonia boonei De Wild. (Apocynaceae) on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Wistar Rats.

Among the most exploited species in Cameroon, Alstonia boonei is widely used in African medicine for the relief of several pathologies including gastrointestinal disorders. This study was conducted in order to assess the effects of aqueous and methanol stem-bark extracts of Alstonia boonei on DSS- (dextran sodium sulfate-) induced intestinal colitis and to determine its antioxidant potential. The classes of secondary metabolites present in these extracts were determined by chemical screening. The production of TNF-α, IL-6, IL-1β, and PGE2 was performed by in vitro ELISA analysis. Anticolitis effects were determined using an in vivo model of ulcerative colitis induced by DSS. The colitis was induced with a double dose of DSS (3% and 1%), and the aqueous and methanol extracts were administered orally from the 6th day after commencement of induction. The phytochemical screening revealed the presence of six classes of secondary metabolites in these crude extracts: tannins, saponins, alkaloids, steroids, flavonoids, and phenols. Methanol and aqueous extracts of Alstonia boonei significantly (P < 0.001) inhibited TNF-α, IL-6, IL-1β, and PGE2 production stimulated by LPS. Both extracts at all doses significantly reduced (P < 0.01, P < 0.001) the signs of DSS-induced colitis in the Wistar rats by decreasing inflammation and chronic colon damage. In addition, the extracts significantly (P < 0.001) reduced malondialdehyde and nitric oxide levels in the colon and significantly (P < 0.01) increased superoxide dismutase and catalase and reduced glutathione (P < 0.05). Both extracts showed greater activity than the reference substance (prednisolone 4 mg/kg) used in this study. This study has demonstrated that aqueous and methanol extracts of Alstonia boonei stem bark have healing properties against colitis experimentally induced by DSS in rats.

Age Adjusted Telomere Length Decreases Following Treatment for Pediatric Acute Lymphoblastic Leukemia, but Does Not Predict Toxicity

IntroductionTelomeres are specialized DNA structures found at the end of linear chromosomes, which in humans contains the repetitive DNA sequence, (TTAGGG)n and associated proteins. Telomere length (TL) is important for replicative capacity of cells, and, in somatic cells, telomere length shortens with each cell division. Once a critically short length is reached, cells enter senescence or undergo apoptosis. In the general population, TL varies greatly and declines with age. Chemotherapy can increase the rate of telomere shortening, although these findings have not been consistently demonstrated. There is evidence, mostly in adults, suggesting that patients with shorter TL experience increased toxicity from cancer treatment. Patients with the short telomere syndrome, Dyskeratosis Congenita undergoing hematopoietic stem cell transplantation have increased rates and degree of organ toxicity when given myeloablative conditioning. In the pediatric population there have been no studies assessing the relationship between TL and rates of toxicity after chemotherapy, and few investigating telomere dynamics following chemotherapy. We undertook a retrospective analysis to investigate the relationship between TL and chemotherapy toxicity, and also telomere dynamics in children treated for acute lymphoblastic leukemia (ALL).MethodsPatients enrolled on the Australian and New Zealand Children's Hematology and Oncology Group's (ANZCHOG) Study 8 for ALL at the Children's Hospital at Westmead and the Sydney Children's Hospital from October 2002 to November 2011 who had provided consent and who had stored samples suitable for TL analysis were included in the study. Organ toxicity information was collected from the Study 8 database, as well as examination of patient medical records and pathology information systems. Liver and renal toxicities were documented based on abnormalities in transaminases, bilirubin and creatinine respectively. Pulmonary and neurotoxicities were determined through medical record and imaging findings. Standard common terminology criteria for adverse events (CTCAE) criteria were used to systematically grade toxicity. Infectious disease information and intensive care admissions as well as time to complete each cycle of therapy were used as surrogate markers for toxicity and bone marrow recovery. Survival and relapse rates were also analyzed.Relative TL was measured using a quantitative PCR technique on DNA extracted from mononuclear cells taken at Day 79 following commencement of induction and consolidation therapy, and also at the end of treatment, typically 24 months from diagnosis. The relative TL was converted to an age adjusted TL (AATL) by subtracting the expected relative TL (i.e. 50th percentile for age of the patient) from the measured relative TL, so that patients of all ages could be analyzed together. For analysis the cohort was separated into four groups based on AATL quartiles.ResultsIn all, 460 patients with research consent were enrolled on ANZCHOG ALL Study 8 at the 2 hospitals included in this study. Of these 157 patients with AATL measurement and toxicity information were included in our analysis with 149 being standard or medium risk. The median age of diagnosis was 4.79 years (range 1.1 - 17.89) with a median follow up of 53 months (range 9-124 months).The median AATL on Day 79 was 0.035 (range -0.41 to 0.73). The average change in TL from day 79 to end of treatment was -0.126 (range -0.81 to 0.40), which is equivalent to approximately 8-10 years of natural ageing. There was no significant association between survival (Figure 1) or rates of grade 3 or 4 organ toxicity, relapse (Table 2) or bone marrow recovery and AATL. Renal toxicity was significantly increased in the second shortest quartile, however numbers are small (4 patients in second quartile vs 1 in fourth quartile).ConclusionThere is an increased rate of telomere attrition during treatment for childhood ALL, however telomere length does not appear to be associated with increased rates of organ toxicity.Support: NHMRC APP1057746 and NHMRC GNT1056667 [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Primary antifungal prophylaxis in adult patients with acute lymphoblastic leukaemia: a multicentre audit.

The primary objectives were to investigate the prescribing practices of primary antifungal prophylaxis (PAP) and incidence of invasive fungal disease (IFD) in adult patients with ALL receiving induction-consolidation chemotherapy. Secondary objectives were to determine risk factors for IFD and resource utilization associated with IFD. A retrospective chart review of adult patients with ALL from commencement of induction until completion of consolidation chemotherapy was undertaken from January 2008 to June 2013 in four hospitals in Melbourne, Australia. IFD was classified according to the revised European Organisation for Research and Treatment of Cancer criteria. Cost analysis was performed from an Australian public hospital perspective. Ninety-eight patients were included in the audit; 83 (85%) received PAP. Most patients (49/83, 59%) switched between two different antifungal agents, predominantly between liposomal amphotericin B and an azole. Five proven/probable and six possible IFD cases were identified. Proven/probable IFD was most common in patients receiving the BFM95 chemotherapy protocol. The incidence of proven/probable IFD was significantly lower in patients receiving PAP compared with those who did not (2/78, 2.6% versus 3/14, 21.4%; P = 0.024). For every five patients receiving PAP, one proven/probable IFD case would be prevented. Proven/probable IFD was associated with an additional median cost of 121,520 Australian dollars (95% CI: 90,781-180,141 Australian dollars; P < 0.001) compared with patients without IFD. This is the first multicentre study evaluating PAP use in patients with ALL. With the caveats of interpretation of retrospective, non-randomized data, PAP was associated with a reduced IFD risk.

Prostaglandin vaginal gel induction of labor comparing amniotomy with repeat prostaglandin gel

The purpose of this study was to compare 2 inductions of labor protocols. Women with live singleton pregnancies at ≥37 + 0 weeks gestation who were booked for prostaglandins 2 (PGE2) vaginal gel induction with a modified Bishop's score of <7 were eligible for inclusion. After an evening dose of PGE2 vaginal gel, women were assigned randomly the next morning into the amniotomy or repeat-PGE2 group. The amniotomy group underwent artificial rupture of membranes (ARM), regardless of modified Bishop's score, and received further PGE2 doses only if ARM was not technically possible. The repeat-PGE2 group received further PGE2 (to a maximum of 3 doses) until a modified Bishop's score ≥7 occurred, when an ARM was performed. In both groups, Syntocinon was commenced once membranes were ruptured. The primary outcome measure was time from commencement of induction until birth. Two hundred forty-five women were assigned randomly into either the amniotomy (n = 121) or repeat-PGE2 group (n = 124). The time for induction of labor-to-birth was >5 hours shorter in the amniotomy group (24.8 vs 30.0 hours; mean difference, 5.2 h; 95% confidence interval, -2.5 to -7.8). Fewer women in the amniotomy group remained undelivered after 24 hours (47.1% vs 67.7%; P < .01). However, the likelihood of an in-hours birth and the length of hospital stay were no different between the groups. There was no difference in the mode of birth or any of the secondary outcomes. After an initial dose of PGE2 vaginal gel, an amniotomy (once technically possible) is associated with a shorter induction of labor-to-birth time compared with the use of repeat doses of PGE2. Administering more PGE2 with the aim of starting contractions or making the cervix "more favorable," appears to have no clinical advantage.

The effect of actinomycin D on the formation of gametangia and mitosporangia in Allomyces.

The effect of actinomycin on gametangium and mitosporangium production in Allomyces arbuscula and A. macrogynus has been investigated. Male gametangium production was not more sensitive to actinomycin than female development. Actinomycin at 20 mug/ml added at the commencement of induction was completely inhibitory. The process became insensitive to actinomycin just before the first septum was laid down.