Lower Disease Intensity Research Articles

The Safety and Efficacy of Oral Magnesium Pidolate in Children with Hemoglobin SC Disease.

An important characteristic of the Hb SC erythrocyte is its high intracellular Hb concentration, which is due to cell K+ loss and dehydration mediated by an abnormally active K-Cl co-transport. This pathologic state of cellular dehydration raises the intracellular concentration of Hb S, thereby increasing its tendency to polymerize. Previous studies in patients with sickle cell disease have shown that oral Mg supplements can increase erythrocyte Mg content, reduce the activity of K-Cl co-transport and diminish erythrocyte dehydration. We performed a randomized, double blind, placebo-controlled study with crossover design on oral Mg supplementation in children with HbSC disease.Methods: Two major pediatric sickle cell centers participated in this IRB-approved study: Texas Children's Sickle Cell Center and The Children's Hospital in Boston. Over 100 eligible patients were contacted and invited to participate. The enrolled patients or their parents/guardians gave informed consent. Patients were randomized to either receive oral Mg pidolate or placebo for 6 months followed by a wash-out period of 2 months, then followed by a 6 month period of the other agent (placebo/Mg pidolate) and 2 months wash-out. Patients were initially followed every 2 weeks, then every 4 weeks. Safety was assessed both by clinical assessment as well as laboratory evaluation, including serum magnesium levels.Results: Between January 2002 and December 2004 we enrolled 12 patients (7 males, 5 female, age range 3.9 to 16.8 years) with HbSC disease and at least one pain crisis within the last year. Only 5 patients are fully evaluable for efficacy assessment. Seven patients came off study for the following reasons: 3 for non-compliance, 2 for study violation (pharmacy dispensed wrong formulation), and 2 withdrew for personal reasons (no longer interested), but all of them were included in the safety assessment. There were 3 events that were considered probably related to study drug (or placebo): diarrhea, grade 2 once and headaches, grade 3, in 2 instances. There were 6 events possibly related to drug (or placebo): diarrhea in three patients (all grade 1) and headaches of grade 2 or 3 in three patients. All adverse events resolved without stopping the drug/placebo. The results of the intracellular Mg concentrations and thus efficacy analysis will be available after unblinding the study in September 2005.Conclusion: Mg pidolate appears to be safe and well-tolerated when used in children with HbSC disease. No serious adverse events occurred that were considered definitively related to the study drug(s). Efficacy results will be available at the time of the meeting. However, despite the fact that study was open at 2 major sickle cell centers and had relatively non-restrictive enrollment criteria, accrual was extremely slow, presumably due to the sporadic and rather low disease intensity of Hb SC disease, and several patients did not complete the study. This should be taken into consideration when designing larger studies for patients with HbSC disease exclusively.

Transgenic expression of hevein, the rubber tree lectin, in Indian mustard confers protection against Alternaria brassicae

The antifungal effect of hevein, the chitin binding lectin from rubber plant ( Hevea brasiliensis), has been analyzed in transgenic plants for potential control of Alternaria blight in Indian mustard caused by Alternaria brassicae. A cDNA encoding hevein was transferred into Indian mustard ( Brassica juncea cv. RLM-198). Southern analysis of the putative transgenics showed integration of the transgene. Northern and Western analyses proved that the integrated transgene is expressed in the transgenics. In whole plant bioassay under glasshouse conditions, transgenics were found to possess parameters that are associated with resistance such as longer incubation and latent period; smaller necrotic lesion size; lower disease intensity and delayed senescence.

Interaction of Ht and Partial Resistance to Exserohilum turcicum in Maize.

Components of northern leaf blight resistance in maize due to race-specific resistance controlled by the Ht gene, partial resistance derived from inbred H99, and a combination of the two kinds of resistance, were studied subsequent to inoculation with Exserohilum turcicum race O. Lesion types, number of lesions (lesion number), percent leaf area affected (severity), and area under the disease progress curve (AUDPC) based on lesion number and severity were assessed in field studies conducted at two locations in Uganda and one location in Ohio in 1993. Lesion types observed were consistent for genotypes across locations. In general, significant differences among genotypes for data based on lesion number and severity were consistent for AUDPC based on lesion number and severity, respectively, at all locations. In Ohio, both Ht and partial resistance were effective in limiting disease development. In Uganda, susceptible inbreds (A619, A635, and B73) generally had higher severity than genotypes with partial resistance (H99, Mo17, and Babungo 3). However, there was a difference in response among genotypes depending on disease intensity at each location. Ht resistance and moderate partial resistance did not greatly affect lesion number at the higher disease intensity location, compared with the susceptible inbreds, but at the lower disease intensity location genotypes with partial resistance had fewer lesions than susceptible inbreds or the Ht conversions of the susceptible inbreds. At both plot locations, genotypes with partial resistance had lower severity than the susceptible inbreds or Ht conversions of the susceptible inbreds. Hybrids derived from crossing H99 with genotypes with moderate levels of partial resistance (Mo17 and Babungo 3) did not have significantly lower lesion numbers than hybrids of susceptible inbreds crossed with H99, but severity was significantly lower on these hybrids at the high disease intensity location. Results indicate that the level of partial resistance in H99 would be as effective in controlling northern leaf blight as using Ht resistance, or a combination of Ht resistance and moderate levels of partial resistance as found in Mo17.

Race non‐specific resistance to Bremia lactucae

SummaryThree ways of measuring race non‐specific resistance to Bremia lactucae in lettuce were studied to determine the most important components of this form of resistance. Tests were conducted on leaf discs from 4–6 wk‐old plants that were quantitatively inoculated and incubated under controlled conditions. Observations were made of disease intensity, latent period and production of conidia. Inoculum concentration markedly influenced disease intensity and latent period. Cv. Iceberg exhibited race non‐specific resistance and this was characterised by a longer latent period, a lower disease intensity and reduced production of conidia compared to the susceptible control cv. Cobham Green. On older, intact plants, the differences in latent period and disease intensity between cultivars were even greater. Production of conidia was a particularly good criterion for discriminating levels of resistance.