Screening of C-kit gene mutation in acute myeloid leukaemia in northern India

Acute Myeloid Leukaemia [AML] is a cancer of blood-forming cells in bone marrow. C-kit gene is a Receptor Tyrosine Kinase class III [RTK] that is expressed by early hematopoietic progenitor cells and plays an important role in hematopoietic stem cell proliferation, differentiation and survival. It is known that c-kit is a proto-oncogene and the activating c-kit mutations are likely to contribute in the development of leukaemia in humans. Exon 11 of c-Kit gene is the frequent site for mutations in different kinds of tumours. In order to determine the frequency and prevalence of exon 11 mutations in 51 AML cases, we have done polymerase chain reaction-single-strand conformational polymorphism followed by direct DNA sequencing. The c-kit mutations in exon 11 were detected in 15.68% [8/51] in AML cases. We have detected totally ten missense mutations in eight AML cases those include Lys550Asn, Tyr568Ser, Ile571Leu, Tyr578Pro, Trp582Ser and Arg588Met and novel missense mutations at codons Ile563Lys and Val569Leu. Mutations at codons Ile571Leu and Trp582Ser was found in two independent cases. The presence of c-kit mutations in our study adds to investigative spectrum of AML cases. Since the c-kit mutations are seen in other malignancies, mutations in exon 11 of the c-kit gene might be involve in pathogenesis and represent useful predictive genetic marker in AML. Further studies in larger group of cases possibly will be required to determine the prognostic implications and to investigate how these mutations are co-related to the progression and pathogenesis of AML

Recent advances in treatment of acute organophosphorous nerve agents poisoning

Organophosphorous [OP] chemical warfare nerve agents mainly sarin and tabun were used during the Iran-Iraq war with high mortalities. In addition to atropine and oximes, the followings have recently been used successfully for the treatment of OP poisoning. 1. Sodium Bicarbonate: Infusion of high doses of sodium bicarbonate [5 mEq/kg in 60 min. followed by 5-6 mEq/kg/day to obtain arterial blood pH of 7.45 to 7.55] revealed positive effects in patients with acute OP poisoning in Mashhad. 2. Magnesium Sulfate: Intravenous magnesium sulfate in a dose of 4 g only on the first day after admission was also effective in acute human OP poisoning. 3. Antioxidants: The toxicity of OP compounds is mediated by generation of nitric oxide and other free radicals. These toxic molecules can be counteracted by antioxidants such as vitamins C and E, spin traps, melatonin and low molecule weight thiols. The latter compounds can also increase the synthesis of glutathione, which can both ameliorate the OP-induced oxidative stress and enhance OP detoxification. It is concluded Sodium bicarbonate, Magnesium sulfate and the antioxidants should be added to the standard treatment of OP poisonings