Subclinical haemorrhagic tendency exists in patients with β-thalassaemia major in early childhood

Background

Alterations of coagulation profile have been reported in patients with β-thalassaemia major (β-TM).

Method

To investigate this in the paediatric population, we studied haemostatic parameters in pre-transfusion blood samples from 50 non-splenectomised transfusion-dependent children with β-TM (mean age 6±2.5 years) and in blood from 25 healthy controls.

Results

Laboratory evaluation showed thrombocytopenia in 40%, prolongation of prothrombin time (PT) in 12% and prolongation of activated partial thromboplastin time (APTT) in 6% of the patients. Mean values for PT, APTT and platelet count (PC) were all raised in the patient population compared with the controls. The alteration of coagulation status was significant for PT (p value <0.005) and APTT (p value <0.0001). However, the change for PC was not significant (p value <0.05). No significant liner correlation could be identified between PT, APTT, PC of the patients and interval between transfusions (in days) or days since last transfusion.

Conclusion

The findings from this study suggest that a subclinical haemorrhagic tendency exists in patients with β-TM at a very early age. The intrinsic pathway appears to be more affected than the extrinsic pathway.     

Fluoride-induced immunotoxicity in adult male albino rat: a correlative approach to oxidative stress

Fluoride pollution in drinking water is an international problem as the fluoride present is often at levels above acceptable limits. In the studies reported here, sodium fluoride (NaF) treatment of rats by gavage for 28 days resulted in the induction of oxidative stress and immunotoxicity. It was shown here that NaF treatment lowered cellular immunity in the rats as illustrated by a significant diminution in peripheral blood lymphocyte, monocyte and neutrophil counts in conjunction with a reduction in splenocyte counts. Effects of NaF treatment on humoral immunity were reflected here in a lowering of the levels of plasma IgG specific to a test antigen (i.e., bovine serum albumin). Disorganization in the histoarchitecture was also noted in the host spleen and thymus after NaF treatment. To determine if oxidative stress was among the potential possible causes for the observed induced immunotoxicities, catalase and peroxidase activities along with malondialdehyde (MDA, product of free radical damage to cells) levels in the spleen and peripheral blood packed cells were also measured. The results indicated that there was a significant diminution in the activities of both the enzymes along with an elevation in MDA levels in both the tissues in treated rats. This report highlights the proposition that chronic exposure to fluoride contaminated drinking water is likely to result in immunotoxicity and, furthermore, that the damage to primary immune organs is due to an induction of oxidative stress.     

Wound pH-responsive sustained release of therapeutics from a poly(NIPAAm-co-AAc) hydrogel

Wound pH strongly influences residence time and activity of various growth factors during wound healing. Hence, a pH-responsive sustained release growth factor delivery system could be beneficial for effective treatment of wound. In this context, an effort was made to evaluate the potential of a poly(N-isopropylacrylamide-co-acrylic acid) hydrogel as pH-sensitive sustained release system for wound-pH-dependent therapeutics delivery. The polymer was synthesized via radical copolymerization and influence of pH on lower critical solution temperature (LCST), microarchitechture and swelling of the hydrogel was evaluated. Results showed a pH-dependent variation in the physical properties of the hydrogel within the wound pH range. Fluorescence recovery after photobleaching (FRAP) analysis endorsed a pH dependent restricted diffusion of the BSA in the hydrogel. Later, release of bovine serum albumin (BSA), vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) (each 5%, w/v) from the hydrogel within the range of wound pH (pH 6.7-7.9) were examined. Analysis showed non-Fickian release of therapeutics from the hydrogel with a significant variation in release rate and cumulative release with the increase in pH. Retention of the bioactivity of the released EGF was confirmed by studying murine dermal fibroblast cell proliferation in vitro. Finally, a growth factor (EGF or VEGF)-loaded hydrogel was applied on a murine excisional wound model and showed augmentation of wound healing in comparison to conventional sustained release growth factor therapy.     

Recombinant Aeromonas hydrophila outer membrane protein 48 (Omp48) induces a protective immune response against Aeromonas hydrophila and Edwardsiella tarda

The gene coding for an outer membrane protein Omp48 of Aeromonas hydrophila isolated from an infected fish was cloned and sequenced. Analysis of nucleotide sequence showed the omp48 gene to be an adhesin encoding a protein of 426 amino acids with high identity to the omp48 gene of Aeromonas veronii, another fish pathogen. The gene belonged to the maltoporin group of porins and had high similarity to LamB porins of A. hydrophila, Aeromonas salmonicida and Vibrio parahaemolyticus. The expressed purified recombinant protein had an estimated molecular weight of 48 kDa. Further, rabbit hyperimmune sera against the recombinant protein reacted with A. hydrophila, Aeromonas sobria and A. veronii whole cell proteins at the region of 48 kDa, in western blotting. The recombinant protein was immunogenic in the fish Labeo rohita Hamilton. Fish immunized with recombinant protein, when challenged with virulent A. hydrophila and another bacterial fish pathogen, Edwardsiella tarda, showed relative percent survivals of 69 and 60, respectively. Our results suggest that Omp48 of A. hydrophila could be used as a potential vaccine candidate for protection not only against A. hydrophila infection, but also against the fish pathogen E. tarda.     

Evaluation of WO2014121383 A1: a process for preparation of rufinamide and intermediates

Introduction: There is great potential in the synthetic development of rufinamide to treat childhood-onset epilepsy known as Lennox–Gastaut syndrome (LGS).

Areas covered: 1,4-disubstituted triazole ring formed by 1,3-dipolar cycloaddition reaction is an important structural motif widely used to construct diverse chemotypes in chemical, biological, and material fields. 1,2,3-triazole ring containing rufinamide, an antiepileptic drug developed by Novartis, is useful in combination with other antiepileptic medicaments for the treatment of childhood-onset epilepsy known as LGS. There are numerous synthetic methods used to construct the rufinamide through 1,3-dipolar cycloaddition. The application claims processes for the preparation of rufinamide and their intermediates. The synthetic strategy covered for the synthesis of rufinamide using activated acetylenic esters. The activation is done using N-hydroxy succinimide, N-hydroxyphthalimide, 1-hydroxy benzotriazole, and 4-nitro phenol.

Expert opinion: The manufacturing route appears to follow the regioselective Cu catalyzed cycloaddtion of 2,6-difluro benzyl azide with or without isolated activated acetylenic esters in three steps that provide a good lead for new synthetic strategy for the rufinamide synthesis.     

Polymerization in the presence of organoaluminum compounds and Azobisisobutyronitrile

The rate of decomposition of azobisisobutyronitrile (AIBN) in methyl methacrylate styrene, and a styrene/methyl methacrylate mixture and the rate of polymerization of the monomers are enhanced in the presence of organoaluminum halides. The monomer-R_xAlX_y interaction influences the rates of both AIBN decomposition and monomer polymerization as well as the polymerization mechanism. The copolymerization of styrene and methyl methacrylate yields alternating copolymers in the presence of AIBN/R_xAlCl_y and random copolymers in the presence of AIBN alone. The AIBN/R_xAlCl_y activated copolymerization occurs in the dark but is accelerated in visible light.     

Addiction to Snake Venom

The nature of addiction depends on various factors. The tendency to have already used several addictive substances and to seek high sensation experiences as a result of specific personality traits may lead to extreme and peculiar forms of addictions. Even belonging to specific social and cultural background may lead to such forms of addiction such as intentional snake bite and willful envenomation. In this article, we have discussed the peculiarities and practical insight of such addiction to snake venom. The possible molecular mechanism behind such venom-mediated reinforcement has also been highlighted. Finally, we have stressed upon the treatment and de-addiction measures.     

Neuroprotective Efficacy of Mitochondrial Antioxidant MitoQ in Suppressing Peroxynitrite-Mediated Mitochondrial Dysfunction Inflicted by Lead Toxicity in the Rat Brain

Lead (Pb) is one of the most pollutant metals that accumulate in the brain mitochondria disrupting mitochondrial structure and function. Though oxidative stress mediated by reactive oxygen species remains the most accepted mechanism of Pb neurotoxicity, some reports suggest the involvement of nitric oxide (^?NO) and reactive nitrogen species in Pb-induced neurotoxicity. But the impact of Pb neurotoxicity on mitochondrial respiratory enzyme complexes remains unknown with no relevant report highlighting the involvement of peroxynitrite (ONOO^?) in it. Herein, we investigated these effects in in vivo rat model by oral application of MitoQ, a known mitochondria-specific antioxidant with ONOO^? scavenging activity. Interestingly, MitoQ efficiently alleviated ONOO^?-mediated mitochondrial complexes II, III and IV inhibition, increased mitochondrial ATP production and restored mitochondrial membrane potential. MitoQ lowered enhanced caspases 3 and 9 activities upon Pb exposure and also suppressed synaptosomal lipid peroxidation and protein oxidation accompanied by diminution of nitrite production and protein-bound 3-nitrotyrosine. To ascertain our in vivo findings on mitochondrial dysfunction, we carried out similar experiments in the presence of different antioxidants and free radical scavengers in the in vitro SHSY5Y cell line model. MitoQ provided better protection compared to mercaptoethylguanidine, N-nitro-L-arginine methyl ester and superoxide dismutase suggesting the predominant involvement of ONOO^? compared to ^?NO and O₂ ^??. However, dimethylsulphoxide and catalase failed to provide protection signifying the noninvolvement of ^?OH and H₂O₂ in the process. The better protection provided by MitoQ in SHSY5Y cells can be attributed to the fact that MitoQ targets mitochondria whereas mercaptoethylguanidine, N-nitro-L-arginine methyl ester and superoxide dismutase are known to target mainly cytoplasm and not mitochondria. Taken together the results from the present study clearly brings out the potential of MitoQ against ONOO^?-induced toxicity upon Pb exposure indicating its therapeutic potential in metal toxicity.