Formulation and characterization of ionically crosslinked gellan gum hydrogels using trilysine at low temperatures for antibody delivery.

Research of the nontraditional polysaccharide gellan gum (GG) is a growing space for the development of novel drug delivery systems due to its tunable physic-mechanical properties, biocompatibility, and stability in a wide range of environments. Unfortunately, high temperature crosslinking is often required, representing a limiting factor for the incorporation of thermosensitive therapeutic agents. Here, we demonstrated that GG can be crosslinked at a low temperature (38 °C) using a simple fabrication process that utilizes trilysine as an alternative to traditional mono- or divalent ion crosslinkers. While elevated temperature mixing is still required to form a clear GG solution, crosslinking of 0.5 - 1 % GG (w/v) in the presence of trilysine (0.03 % - 0.05 % w/v) was achieved at 38 °C resulting in hydrogels with suitable working formulations to facilitate syringe loading. Low injection forces (< 20 N), and biocompatibility was evaluated with normal human dermal fibroblast (cell viability > 90 %). Frequency sweep showed a transition from purely liquid-like behavior to gel-like behavior with increased trilysine concentration. A temperature dependent behavior was lost with higher trilysine concentrations, indicating stable hydrogel formation. NMR results suggest that trilysine participates in gelation via both ionic interactions between the primary amines of trilysine and the carboxylate residues of glucuronic acid and hydrogen bonding. Released studies showed that GG hydrogels can entrap and provide sustained release of IgG in relation to the crosslinker, and antibody concentration used, with a burst release within the first 24 h (∼80 % cumulative released) followed by a sustained released for up to 5 days. Overall, findings demonstrate a promising nontoxic injectable hydrogel that requires lower crosslinking temperatures, is simple to manufacture and serves as a carrier of thermosensitive therapeutic agents.

A curious case of pulmonary hypertension in a child.

BACKGROUND: Pulmonary hypertension in young children can be due to a myriad of conditions. Few aetiologies of pulmonary hypertension are potentially reversible. An extensive workup for the cause of pulmonary hypertension is a must before attributing it to idiopathic pulmonary hypertension. We describe an uncommon aetiology of pulmonary hypertension in a young boy. CASE PRESENTATION: A 12-year-old child, with past history of tubercular pleural effusion, presented with dyspnoea on exertion and easy fatiguability for 2 years. He was evaluated elsewhere and was being treated as primary pulmonary hypertension with pulmonary vasodilators. The child was revaluated since the clinical features were not completely favouring the diagnosis. On detailed evaluation, a diagnosis of constrictive pericarditis was made. He was referred for pericardiectomy. CONCLUSIONS: Constrictive pericarditis presenting with severe pulmonary hypertension without congestive symptoms is very rare. In patients presenting with pulmonary hypertension, always look for a reversible cause before labeling them as idiopathic PAH.

Unusual presentation of mitral prosthetic heart valve thrombosis managed with low dose tenecteplase infusion.

A 11-year-old with history of mitral valve replacement presented with low-grade fever, breathlessness and multiple episodes of haemoptysis for 2 days. Detailed echocardiographic evaluation revealed possible prosthetic valve thrombosis, which was confirmed by fluoroscopy. She was thrombolysed with low dose infusion of tenecteplase. Post thrombolysis her symptoms improved, valve mobility was restored, and haemoptysis subsided. Left sided prosthetic valve thrombosis presenting predominantly with haemoptysis is very rare.

Mechanism of action of a desensitizing fluoride toothpaste delivering calcium and phosphate ingredients in the treatment of dental hypersensitivity. Part II: comparison with a professional treatment for tooth hypersensitivity.

Tooth hypersensitivity can occur when gum recession causes exposure of dentin. Tiny tubules, which permeate dentin, provide open passageways from the mouth to the intradental nerve in the pulpal cavity. Under such circumstances, stimuli in the mouth can cause pressure on the intradental nerve, leading to pain. Sealing the outside of the tubules with an impermeable substance can effectively treat hypersensitivity. One such clinically proven composition is a professionally applied tooth desensitizer, which has been shown to initially produce a layer of amorphous calcium phosphate (ACP) on the surface of dentin. Under the influence of fluoride, ACP reforms as hydroxyapatite (HAP), which has essentially the same composition as tooth mineral. Three fluoride toothpastes that deliver calcium and phosphate salts to the teeth also have been demonstrated in clinical trials to relieve hypersensitivity. This study compared the mechanism of action of these toothpastes to that of the professional desensitizer. A single application of the professional desensitizer or multiple applications of any of the three toothpastes was shown to reduce dentin permeability. A conventional fluoride toothpaste also was found to inhibit fluid flow through the dentin but to a lesser degree than the other toothpastes. The desensitizer and the three toothpastes were found to occlude the dentinal tubules with a layer of calcium phosphate that had a calcium-to-phosphate ratio consistent with the formation of ACP or HAP. The morphology of the coherent mineral layer formed by Arm & Hammer Enamel Care Sensitive was similar, especially to that produced by the desensitizer. In contrast, the conventional toothpaste left localized areas of surface residue composed of silica particles. The mechanism of action of the three toothpastes that deliver calcium and phosphate salts is the same as that of the professional desensitizer.