Formulation development and in-vitro evaluation of Molsidomine matrix tablets for colon specific release

Colon targeted tablets were prepared in two steps. Initially core tablets were prepared and then the tablets were coated by using different pH dependent polymers. Ethyl cellulose, Eudragit L100 and S100 were used as coating polymers. FT-IR studies were carried out to find out the possible interaction between the selected drugs and polymer. FT-IR studies revealed that there  was  no  interaction between the selected drug and excipients. The pre-compression blend of all formulations was subjected to various flow property tests and all the formulations passed the tests. The tablets were coated by using polymers and the coated tablets were subjected to various evaluation techniques. The tablets passed all the tests. Among all the formulations F3 formulation was found to be optimized as it was retarded the drug release up to 12 hours and showed maximum of 97.57% drug release. It followed zero order kinetics mechanism. The ideal formulation was subjected to stability studies at 40°C/75%RH. The stability studies indicated that the formulation was stable and retained its pharmaceutical properties at 40°C/75%RH over a period of 1 month. Keywords: Colon target, Ethyl cellulose, Eudragit L100 and S100, pH dependent polymers

A factor in a wild-isolated Neurospora crassa strain enables a chromosome segment duplication to suppress repeat-induced point mutation (RIP)

Repeat-induced point mutation (RIP) is a sexual stage-specific mutational process of Neurospora crassa and other fungi that alters duplicated DNA sequences. Previous studies from our laboratory showed that chromosome segment duplications (Dps) longer than ~300 kbp can dominantly suppress RIP, presumably by titration of the RIP machinery, and that although Dps <200 kbp did not individually suppress RIP, they could do so in homozygous and multiply heterozygous crosses, provided the sum of the duplicated DNA exceeds ~300 kbp. Here we demonstrate suppression of RIP in a subset of progeny carrying the normally sub-threshold 154 kbp Dp(R2394) from a cross of T(R2394) to the wild isolated Carrefour Mme. Gras strain (CMG). Thus, the CMG strain contains a factor that together with Dp(R2394) produces a synthetic RIP suppressor phenotype. It is possible that the factor is a cryptic Dp that together with Dp(R2394) can exceed the size threshold for titration of the RIP machinery and thereby causes RIP suppression

Mechanism of nickel resistance in a cobalt-resistant wall-less mutant of <i>Neurospora crassa (fz; sg; os-1)</i>

1117-1122A cobalt-resistant wall-less mutant of N. crassa (Cor-sl) characterized previously was also found to be 3-fold more resistant to nickel when compared to the parent wall-less mutant (W-sl). The Cor-sl strain accumulates relatively lower amounts of nickel when compared to W-sl. Sub-cellular fractionation showed significant quantities of nickel to be associated with nuclear and mitochondrial fractions in both the wall-less mutants. However significant differences were observed in vacuolar fractions of W-sl and Cor-sl strains. Fractionation of cell-free extracts on .Sephadex G-10 column resolved nickel into two peaks, of which the peak II in Cor- sl constituted 70% of nickel, while the same in W-sl was about 30%. A 3-fold increase in histidine content was observed in case of Cor-sl as compared to W-sl strain, suggesting its role in Ni-resistance

Meiotic silencing by unpaired DNA is expressed more strongly in the early than the late perithecia of crosses involving most wild-isolated Neurospora crassa strains and in self-crosses of N. tetrasperma

Meiotic silencing by unpaired DNA is a presumed RNAi-mediated elimination of the transcripts of any gene that is not properly paired with a homolog in meiosis. Eighty wild-isolated strains of Neurospora crassa were classified into three types based on the apparent strength of meiotic silencing of the bml (β-tubulin) and mei-3 genes in crosses with the ::Bmlr and ::mei-3 tester strains. "OR" and "Sad" type wild-isolates, respectively, did or did not silence both the genes, whereas the "Esm" type (68 strains) silenced bml but not mei-3+, suggesting an intermediate strength of silencing. Many wild strains, especially of the Esm type, gave fertile crosses with strains bearing the 148 kbp chromosome segment duplication Dp(EB4) but their crosses with the 405 kbp Dp(IBj5) were barren. Larger Dps might include more genes whose sensitivity to silencing is comparable with that of bml, consequently their crosses with the OR and Esm type strains would be about equally barren, whereas small Dps, with presumably few or no bml-like genes suffer little gene silencing in crosses with Esm and Sad strains and thus remain fertile. Using lollipop-shaped asci as indicators of silencing in crosses of the ::act tester with Esm type strains, and white-spored asci in Neurospora tetrasperma self-crosses heterozygous for an ectopic insertion of the asm-1 gene, we found that meiotic silencing was expressed more strongly in the early but not in the late perithecia of these crosses