Subcutaneous injection of an immunologically tolerated protein up to 5 days before skin injuries improves wound healing.

Oral tolerance blocks the development of specific immune responses to proteins ingested by the oral route. One of the first registries of oral tolerance showed that guinea pigs fed corn became refractory to hypersensitivity to corn proteins. Mice fed with chow containing corn are tolerant to zein, and parenteral injection of zein plus adjuvant blocks immunization to unrelated proteins injected concomitantly and reduces unspecific inflammation. Extensive and prolonged inflammatory infiltrate in the wound bed is one of the causes of pathological wound healing. Previous research shows that intraperitoneal injection of zein concomitant with skin injuries reduces the inflammatory infiltrate in the wound bed and improves wound healing. Herein, we tested if one subcutaneous injection of zein before skin injury improves wound healing. We also investigated how long the effects triggered by zein could improve skin wound healing. Mice fed zein received two excisional wounds on the interscapular skin under anesthesia. Zein plus Al(OH)3 was injected at the tail base at 10 min, or 3, 5, or 7 days before skin injuries. Wound healing was analyzed at days 7 and 40 after injury. Our results showed that a zein injection up to 5 days before skin injury reduced the inflammatory infiltrate, increased the number of T-cells in the wound bed, and improved the pattern of collagen deposition in the neodermis. These findings could promote the development of new strategies for the treatment and prevention of pathological healing using proteins normally found in the common diet.

Subcutaneous injection of an immunologically tolerated protein up to 5 days before skin injuries improves wound healing

Oral tolerance blocks the development of specific immune responses to proteins ingested by the oral route. One of the first registries of oral tolerance showed that guinea pigs fed corn became refractory to hypersensitivity to corn proteins. Mice fed with chow containing corn are tolerant to zein, and parenteral injection of zein plus adjuvant blocks immunization to unrelated proteins injected concomitantly and reduces unspecific inflammation. Extensive and prolonged inflammatory infiltrate in the wound bed is one of the causes of pathological wound healing. Previous research shows that intraperitoneal injection of zein concomitant with skin injuries reduces the inflammatory infiltrate in the wound bed and improves wound healing. Herein, we tested if one subcutaneous injection of zein before skin injury improves wound healing. We also investigated how long the effects triggered by zein could improve skin wound healing. Mice fed zein received two excisional wounds on the interscapular skin under anesthesia. Zein plus Al(OH)3 was injected at the tail base at 10 min, or 3, 5, or 7 days before skin injuries. Wound healing was analyzed at days 7 and 40 after injury. Our results showed that a zein injection up to 5 days before skin injury reduced the inflammatory infiltrate, increased the number of T-cells in the wound bed, and improved the pattern of collagen deposition in the neodermis. These findings could promote the development of new strategies for the treatment and prevention of pathological healing using proteins normally found in the common diet.

Rate of feed passage in Japanese quail.

The rate of passage (ROP) in the gastrointestinal tract (GIT) influences the exposure time of food to the digestion and absorption processes. Consequently, ROP affects the efficiency of nutrient utilization and energy from the diet. This study aimed to determine the physiological parameters that characterize the digestive response, such as first appearance time (FAT), ROP, mean retention time (MRT) and transit time (TT) in adult Japanese quail (Coturnix coturnix japonica), and to evaluate the effects of sex, apparent metabolizable energy corrected for nitrogen balance (AMEn) content in the diet and different types of markers on these parameters. In the first trial, we investigated the effects of sex and AMEn level (high- and low-energy diet) on the FAT parameter. Thirty-two male and 32 female Japanese quail were randomly allocated to 8 battery cages and assigned to 4 treatments in a 2 × 2 factorial design with 4 replicates of 4 birds for each treatment. To determine the FAT, ferric oxide (1%) was added to the diet, and the excreta of the quail was monitored until the first appearance of the marker. The results indicated significant differences (P < 0.05) in the FAT between males (100 min) and females (56 min), regardless of the AMEn content. In the second trial, thirty-two 32-week-old female Japanese quail in the laying phase were assigned to four treatments in a 2 × 2 factorial design, in which the main independent variables were type of marker (Cr or Ti) and AMEn level (high- and low-energy diets). In order to determine ROP (ET1%), MRT and TT (ET100%), the markers (0.5%: Cr2O3 and 0.5%: TiO2) were added to the diets, and the excreta were collected for 750 min. The excretion times for 1% (ET1%), 25% (ET25%), 50% (ET50%), 75% (ET75%) and 100% (ET100%) were estimated using cumulative excretion curves. No effect was detected for the AMEn level (P > 0.05); however, the effect of different marker types was significant (P < 0.05). This difference increased with time and ET100% was estimated to occur at 59 min. The ROP was estimated to be 68 min. The TT was estimated to be 540 min using Cr and 599 min using Ti, with an average MRT value of 0930 h. Taken together, our findings support the hypothesis that Japanese quail digestion through the GIT can be dynamic and differ based on sex or marker type.

Combination of cetuximab with chemoradiation, trastuzumab or MAPK inhibitors: mechanisms of sensitisation of cervical cancer cells.

BACKGROUND: Cervical cancer (CC) annually kills 288,000 women worldwide. Unfortunately, responses to chemoradiation are partial and are of short duration. As anti-EGFR monoclonal antibodies sensitise tumours, we investigated cetuximab's toxicity plus chemoradiation on CC cells, which express different EGFR levels. METHODS: EGFR, HER2, AKT and MAPK expression and phosphorylation status were determined by western blotting. Cytotoxicity was assessed by MTT or clonogenic assays (CA) in cell lines treated with cetuximab alone or in combinations. RESULTS: Cetuximab with cisplatin and radiation achieved maximum cytotoxic effects for A431, Caski and C33A cells (high, intermediate and low EGFR expression, respectively) in CA. Cetuximab efficiently decreased MAPK and AKT phosphorylation in A431 cells but slightly less in Caski and C33A cells. To check whether further EGFR, HER2 or MAPK inhibition would improve cetuximab's cytotoxicity, we combined it with an EGFR tyrosine kinase inhibitor (TKI), trastuzumab or a MEK1/2 inhibitor (PD98059). In Caski, but not in C33A cells, cetuximab cooperated with the TKI, reducing cell survival and AKT and MAPK phosphorylation. However, cetuximab with trastuzumab or PD98059 reduced survival and MAPK phosphorylation of both cell lines. CONCLUSION: Our data suggest that cetuximab combined with chemoradiation, trastuzumab or MAPK inhibitors has useful applications for CC treatment, independently of EGFR expression.