Effect of rumen-protected nutrients on feed intake, body weights, milk yield, and composition in Murrah buffaloes during early lactation.

The effect of rumen-protected nutrients (bypass fat, BPF; bypass protein, BPP; or their combination, BPPF) was investigated in Murrah buffaloes during the early stage of lactation. Forty Murrah buffaloes (BW 531.92 ± 10.85 kg) just after parturition were randomly distributed into four groups according to parity and milk production. Buffaloes individually fed ration from day 0 to 90 postpartum according to feeding group and nutrient requirement. Control and BPF fed groups received a concentrate mixture, CM1 with 25% rumen-protected protein (using barley, wheat bran, and mustard oil cake), BPP and BPPF groups received a second concentrate mixture, CM2 with 40% rumen-protected protein (using barley, de-oiled rice bran, and cottonseed cake). Bypass fat fed groups (BPF and BPPF) additionally were supplemented with 15 g BPF (Ca salt of long-chain fatty acids) per kg milk yield in their respective concentrate mixtures. Dry matter intake, body weights, body condition score, and total milk yield were similar between groups (P > 0.05). Fat-corrected milk (FCM) production was improved (14.5%, P > 0.05) in groups fed BPP and BPPF, while significant (19.45%, P < 0.05) improvement was observed in BPF-fed group. Overall mean values of milk fat, solid not fat, protein, lactose, and total solids were found to be high (P < 0.05) in treatment groups as compared with control values. It may be concluded that supplementation with BPP or BPF either alone or in combination positively influences the quality of milk produced in Murrah buffaloes during early lactation and BPF additionally had improvement on the quantitative trait of milk as well.

An update on the animal studies conducted for biosimilar approvals - Regulatory requirement vs actual scenario.

Nonclinical animal studies are considered as an integral part of biosimilar development program to demonstrate similarity and safety. We have compiled, reviewed and summarized animal studies conducted for European Medicines Agency (EMA) and United States Food and Drug Administration (US FDA) submission from 2006 till December 2018. The commonest animal studies conducted included repeat-dose toxicity study along with toxicokinetic, local tolerance and immunogenicity assessments, while the least common included primary pharmacodynamic, pharmacokinetic, safety pharmacology and single-dose toxicity studies. Animal studies were designed based on pharmacology of the drug, disease condition and innovator studies. Studies mostly used EU-sourced reference products as a comparator. For biosimilars approved both in the US and European Union (EU), similar data packages were submitted to these regions. Despite the regulatory guidelines allowing waiver of animal studies based on analytical data, animal studies have been conducted for almost all the approved biosimilars in the US and EU. There is an increasing need to re-assess the relevance of animal studies to support regulatory approval of biosimilars. Stepwise assessment for biosimilarity and conducting animal studies only if required at the right instance based on residual uncertainties may assist in optimizing animal study requirement for biosimilar development.

An evaluation of crude palm oil (CPO) and tocotrienol rich fraction (TRF) of palm oil as percutaneous permeation enhancers using full-thickness human skin.

The drawbacks associated with chemical skin permeation enhancers such as skin irritation and toxicity necessitated the research to focus on potential permeation enhancers with a perceived lower toxicity. Crude palm oil (CPO) is obtained by direct compression of the mesocarp of the fruit of the oil palm belonging to the genus Elaeis. In this research, CPO and tocotrienol-rich fraction (TRF) of palm oil were evaluated for the first time as skin permeation enhancers using full-thickness human skin. The in vitro permeation experiments were conducted using excised human skin mounted in static upright 'Franz-type' diffusion cells. The drugs selected to evaluate the enhancing effects of these palm oil derivatives were 5-fluorouracil, lidocaine and ibuprofen: compounds covering a wide range of Log p values. It was demonstrated that CPO and TRF were capable of enhancing the percutaneous permeation of drugs across full-thickness human skin in vitro. Both TRF and CPO were shown to significantly enhance the permeation of ibuprofen with flux values of 30.6 µg/cm2 h and 23.0 µg/cm2 h respectively, compared to the control with a flux of 16.2 µg/cm2 h. The outcome of this research opens further scope for investigation on the transdermal penetration enhancement activity of pure compounds derived from palm oil.

Effects of three different doses of a fruit extract of Terminalia chebula on metabolic components of metabolic syndrome, in a rat model.

There is documented evidence of the use of Terminalia chebula for various ailments in the Ayurvedic literature. The extract has been shown to possess glucose lowering activity and to improve insulin sensitivity in animal models of type 2 diabetes mellitus. The present study was carried out to study the dose response relationship of this extract in a rat model of metabolic syndrome. Six groups of rats were fed a high fructose diet (HFD) for a period of 20 days to induce metabolic syndrome. Three doses of fruit extract of T. chebula 50, 100 and 200 mg/kg were administered orally and pioglitazone 2.7 mg/kg was used as a positive control. Blood samples were collected at days 0, 20 and 40 from the tail vein. Systolic blood pressure (SBP) was measured using the tail cuff method and an oral glucose tolerance test (OGTT) was done on the day of blood collection. Administration of HFD for 20 days significantly increased fasting blood glucose (FBG), SBP and the area under the curve of OGTT. On day 40 the FBG in the 50, 100 and 200 mg/kg group was 97.33 +/- 5.82 (NS), 86.83 +/- 5.08 (p = 0.038) and 85.67 +/- 6.74 (p = 0.15), respectively. These results show that the fruit extract of T. chebula exerts a significant and dose-dependent glucose lowering effect in the rat model of metabolic syndrome.