ABSTRACT
Liquid protein formulations are prone to form aggregates. The effect of nonionic surfactants such as Polysorbate 20 [PS 20] and n-Dodecyl beta-D-maltoside [DDM] on the prevention of aggregation and conformational changes of recombinant human IFNbeta-1b [rhIFN beta_1b] was explored. Polysorbate has been used in formulations of protein pharmaceuticals. There have been concerns about using PS 20 due to its residual peroxide content which may negatively affect protein efficacy. n-Dodecyl beta-D-maltoside has been of interest and shown to be highly effective in prevention of aggregation. Fresh bulk of rhIFN beta_1b was formulated using DDM or different concentrations of PS 20. Formulations were exposed to light stress condition according to the ICH guideline of Q1b. The overall conformational integrity of individual samples was characterized by a combination of Circular dichroism [CD], Fluorescence spectroscopy and RP_HPLC techniques. The CD spectrum depicting the conformational integrity of rhIFN beta_1b showed 31.9% and 31.2% decreases in alpha-helix content of protein samples with 0.2% or 0.02% of PS20 compared to only18.2% of that containing 0.2% DDM. The RP-HPLC analysis also showed that the oxidized impurity in formulation containing DDM is less than those contain PS 20. Complementary analysis of the liquid formulations using IFR and UV methods also was in compliance with the data obtained by CD. Compared to PS 20, the sample of rhIFN beta_1b formulation with DDM was more resistant to the destruction effect of light. Results were in accordance with previous studies and could suggest DDM as a reliable anti-aggregation surfactant in biopharmaceutical formulations
ABSTRACT
The ratio of omega -6: omega -3 is connected to the higher risk of non-communicable diseases, thus this ratio is becoming more important than quantity of omega -6 and omega -3 in human nutrition. In countries like Iran, cow's milk is mainly produced in rural area and less in conventional systems. The lactating cows reared in rural and conventional farms are different in terms of nutrition, daily yields, and proportion of concentrate to forage that these might affect milk fatty acid profiles. Therefore, the aim of this study was to determine the ratio of omega -6: omega -3 in cow's milk produced in conventional and rural dairy farms in west of Iran, Khorramabad. Twenty bulk milk samples [rural and conventional] were collected from the conventional dairy farms and local milk collection centers. Fatty acid profiles were determined and results showed that conventional milk had higher omega -6 [2.1+/- 0.4] and lower omega -3 [0.16 +/- 0.03] in comparison with rural milk. The ratio of omega -6:omega -3 in rural milk was significantly lower [8:1] than that in conventional milk [13:1] [p<0.01]. In conclusion, milk produced in rural dairy farms had better ratio of omega -6:omega -3, thus rural milk could be healthier for human nutrition in terms of omega -3 fatty acids
ABSTRACT
Anticonvulsant activity of 7-phenyl-5H-thiazolo[5, 4-e][1, 2, 3, 4]tetrazolo[5, 1-c]pyrrolo[1, 2-a][1, 4]diazepine [5] and 7-phenyl-5H-thiazolo[5, 4-e][1, 3, 4]triazolo[5, 1-c]pyrrolo[1, 2-a][1, 4]diazepines [6a-d] was measured against pentylenetetrazole [PTZ]-induced seizures in mice. Intraperitoneal injections of different doses [12.5, 25 and 50 mg/kg, i.p.] of test compounds decreased PTZ-induced seizure significantly in a dose-dependent manner.The test compounds were administered 30 min befor PTZ [80 mg/kg, i.p.] injection. The maximum response was obtained with 50 mg/kg of compound 6d that showed more anticonvulsant activity compared to diazepam [0.5 mg/kg]. The frequency of mortality was also decreased by all listed compounds. Pretreatment of animals with flumazenile [as a benzodiazepine, BDZ receptor antagonist] decreased, but not completely inhibited the anticonvulsant activity of compound 6d [50 mg/kg]. These results indicate that besides BZD receptors, other neurotransmitter systems may be involved in anticonvulsant activity of the tested compounds