Cod Liver Oil,but Not Retinoic Acid,Treatment Restores Bone Thickness in a Vitamin A-Deficient Rat

Vitamin A plays a prominent role for maintaining optimal bone status, but its impact upon the bone in response to vitamin A deficiency is not well defined. The purpose of this study was to evaluate how replenishing vitamin A by either whole food cod liver oil (COD) or the active metabolite of vitamin A, retinoic acid (RA), altered bone thickness of vitamin A-deficient (VAD) rats. Weanling rats were administered a control diet (CTRL) or VAD diet for 9 weeks. This was followed by four weeks of treatment in which the VAD group was divided into the following 4 subgroups: (1) VAD (9 weeks)-VAD (4 weeks); (2) VAD-CTRL; (3) VAD-COD; and (4) VAD-RA. Compared to controls, VAD rats had thicker bones which showed marked dysplasia. VAD-rats treated with COD produced a thinner bone that was not significantly different from that of untreated rats. In contrast, RA did not significantly change the thicker bone, and also had significantly greater periosteal and endosteal osteoblast numbers compared to VAD-COD. Active osteoclasts were not detected in VAD rats, nor during the treatment period. These findings suggest that the abnormal bone thickness in VAD rats appears to be more effectively restored to bone thickness of untreated control rats when treated with COD.     

Suppression of Sulfate-Induced Expansion with Lime–Silica Fume Blends

Sulfate-induced expansion resulting from the formation of ettringite in sulfate-bearing soil stabilised with calcium-based stabilisers is a problematic issue with technical and economic implications. Thus, this research examines the viability of the co-addition of lime (L) and silica fume (S) at varying binder dosages (4, 6, and 10 wt%), with a view of establishing the optimum blend of L–S for suppressing the ettringite-induced expansion of artificially high sulfate-dosed soil (kaolinite-K and gypsum-G). To do so, a series of laboratory specimens, designed using different gypsum and lime concentrations, were investigated using unconfined compression strength (UCS), linear expansion, and derivative thermo-gravimetric analysis (DTG) as the main criteria for the examination. The research outcomes indicated that the increasing substitution of L with S induces a gradual reduction on the UCS and linear expansion at binder levels of 4 and 6 wt%, while its usage in a high binder level (10 wt%), can yield an expansion reduction, with no compromise on the UCS performance. Therefore, silica fume has the potential for restricting ettringite formation and suppressing the expansion, of which 3L7S is the optimum blending ratio for suppressing the expansion.     

Home Use of Mini-Dose Glucagon As a Novel Treatment for Hypoglycemia Following Repeated,Prolonged Fasts in Type 1 Diabetes During Ramadan

OBJECTIVEWe determined the efficacy of self-administered subcutaneous mini-dose glucagon (MDG) to treat fasting-induced hypoglycemia in type 1 diabetes (T1D).RESEARCH DESIGN AND METHODSThis was a 4-week randomized, controlled crossover trial of 2-week MDG or 2-week oral glucose tablets (OG, control) involving 17 adults with T1D during Ramadan.RESULTSCompared with OG, MDG demonstrated a significant higher change in blood glucose from baseline to 30 min (Δ^t30, P < 0.001) and 1 h (Δ^t60, P = 0.02). The efficacy of MDG was preserved following ≥8 h fasting with significantly higher Δ^t30 in MDG (P = 0.01). Over the entire 2 weeks, MDG period had increased time in 70–180 mg/dL (P = 0.009) and less time <70 mg/dL (P = 0.04). MDG use resulted in higher completion of fasts compared with OG (P < 0.001).CONCLUSIONSMDG administration is an effective alternative to OG for prevention and treatment of fasting-induced hypoglycemia, offering improved glycemic control and promoting successful completion of prolonged fasts.     

Enhancement of antigen-specific interleukin 2 production by adding liposomes to rabies antigens for priming

Antigen-specific IL-2 production was assessed, using splenocytes from rabies immune mice incubated for 24 h with rabies virus antigen. The antigenic material used for in vivo priming was either purified glycoprotein from rabies virus, or the inactivated virus. The time between priming, harvesting and restimulation of the splenocytes was 7 days. It was found that when antigenically inert liposomes were injected, together with antigenic material, to the prospective splenocyte donor mice, IL-2 production was enhanced. This augmentation was observed particularly when priming was performed with the inactivated rabies virus.     

Targeting oncogenic interleukin‐7 receptor signalling with N‐acetylcysteine in T cell acute lymphoblastic leukaemia

Activating mutations of the interleukin‐7 receptor (IL7R) occur in approximately 10% of patients with T cell acute lymphoblastic leukaemia (T‐ALL). Most mutations generate a cysteine at the transmembrane domain leading to receptor homodimerization through disulfide bond formation and ligand‐independent activation of STAT5. We hypothesized that the reducing agent N‐acetylcysteine (NAC), a well‐tolerated drug used widely in clinical practice to treat acetaminophen overdose, would reduce disulfide bond formation, and inhibit mutant IL7R‐mediated oncogenic signalling. We found that treatment with NAC disrupted IL7R homodimerization in IL7R‐mutant DND‐41 cells as assessed by non‐reducing Western blot, as well as in a luciferase complementation assay. NAC led to STAT5 dephosphorylation and cell apoptosis at clinically achievable concentrations in DND‐41 cells, and Ba/F3 cells transformed by an IL7R‐mutant construct containing a cysteine insertion. The apoptotic effects of NAC could be rescued in part by a constitutively active allele of STAT5. Despite using doses lower than those tolerated in humans, NAC treatment significantly inhibited the progression of human DND‐41 cells engrafted in immunodeficient mice. Thus, targeting leukaemogenic IL7R homodimerization with NAC offers a potentially effective and feasible therapeutic strategy that warrants testing in patients with T‐ALL.