Optimization,in vitro release and toxicity evaluation of novel pH sensitive itaconic acid-g-poly(acrylamide)/sterculia gum semi-interpenetrating networks

BackgroundIn recent era, pH sensitive polymeric carriers that combines the materials engineering and medicine is gaining researcher’s attention as they maximizes drug concentration at site of absorption and reduces side effects for e.g. orally administered cetirizine HCl (CTZ HCl) upsets the stomach and furthermore shows high intestinal absorption. Thus, development of pH sensitive hydrogels with sufficient mechanical strength will be good candidate to address this issue.MethodsHere, we developed pH sensitive itaconic acid-g-poly(acrylamide)/sterculia gum (IA-g-poly(AM)/sterculia gum) semi-interpenetrating network (semi-IPN) by free radical polymerization technique for intestinal delivery of CTZ HCL.ResultsOptimized formulation (I5) with 6% w/w IA showed negligible swelling at pH 1.2, and maximum swelling at pH 7.4. Solid state characterization of optimized formulation showed successful development of semi-IPN structure and incorporation of drug without any noticeable drug-carrier interaction. In vitro release study showed biphasic pH dependent release of CTZ HCl, where initial burst release was observed at acidic pH followed by sustained release at basic pH. Acute oral toxicity and histopathological studies confirmed the non-toxic nature of IA-g-poly(AM)/sterculia gum.ConclusionConclusively, developed biocompatible semi-IPN hydrogels with sufficient pH sensitivity and mechanical strength could serve as a potential carrier for intestinal delivery of CTZ HCL to maximize its absorption and reduce side effects.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s40199-021-00395-8.     

Living-related liver transplantation for Crigler-Najjar syndrome in Saudi Arabia

OBJECTIVE: To analyse the outcome of six children with Crigler-Najjar syndrome type I (CNS-I) and report the first three living-related liver transplants for this syndrome in Saudi Arabia and the Middle East. SETTINGS: To review the medical records of six children suffering from CNS-I, three of whom underwent living-related liver transplantation (LRLT) between 22 November 1998 and January 2001. MAIN RESULTS: Living-related liver transplantation was performed in three children with a pre-transplant unconjugated bilirubin level of 362, 381 and 502 micromol/L, respectively, despite daily phototherapy of >or= 12 h. Two of the transplanted children developed acute hepatocellular rejection, which was successfully treated with methylprednisolone pulse therapy. One tested cytomegalovirus positive (using the PP65 method), but showed no signs of clinical infection and was treated with ganciclovir. One patient had a biliary leak at the cut surface of the graft which was surgically repaired. Post-operative bilirubin levels returned to normal in all three transplanted children and no further phototherapy was required. One patient, who was not transplanted but received phototherapy, developed severe neurological damage prior to the start of our living-related liver transplant programme with a bilirubin level of 450 micromol/L, her sister is still awaiting transplantation. A 14-yr-old child with a bilirubin level of 420 micromol/L is presently undergoing phototherapy whilst awaiting orthotopic liver transplantation because of the lack of a suitable living-related donor. Six siblings of the six children in our series were reported dead by the families. CONCLUSION: Crigler-Najjar syndrome type I is a relatively common disease in Saudi Arabia for which LRLT is a curative treatment when performed at an early age before the development of kernicterus and neurological deficiency. In countries where there is a severe shortage of cadaveric organs, as is the case in Saudi Arabia, LRLT is the optimum treatment modality for this syndrome.     

Using electroactive substrates to pattern the attachment of two different cell populations

This report describes the development of an electroactive mask that permits the patterning of two different cell populations to a single substrate. This mask is based on a self-assembled monolayer of alkanethiolates on gold that could be switched from a state that prevents the attachment of cells to a state that promotes the integrin-mediated attachment of cells. Monolayers were patterned into regions having this electroactive monolayer and a second set of regions that were adhesive. After Swiss 3T3 fibroblasts had attached to the adhesive regions of this substrate, the second set of regions was activated electrically to permit the attachment of a second population of fibroblast cells. This method provides a general strategy for patterning the attachment of multiple cell types and will be important for studying heterotypic cell-cell interactions.     

Posterior fossa arachnoid cyst presenting with unilateral tremor

A rare case of unilateral benign essential tremor is presented that responded to surgical excision of a posterior fossa arachnoid cyst.     

Atrial Fibrillation in Patients with Constrictive Pericarditis: The Significance of Pericardial Calcification

Background: Although atrial fibrillation (AF) is commonly encountered in patients with constrictive pericarditis (CP), little has been done to clarify its associated predisposing factors. Our aim was to evaluate the association of age, gender, disease duration, and pericardial calcification with AF in these patients. Methods: The medical records of 44 patients with CP were reviewed. There were 13 (29.5%) with AF and 31 (70.5%) with sinus rhythm. The two groups were compared for demographic variables, disease duration, and the presence of pericardial calcification. Results: The male‐to‐female ratio was 3.4:1. Calcification was seen in 11 (25%) of the entire group. AF was much more common in those with calcification than those with sinus rhythm (odds ratio, 7.87 [95% CI, 1.73–35.78], P = 0.008). There was no association between the presence of AF and the age (P = 0.156) or gender (P ≈ 1.00). Logistic regression, however, showed that the chance of developing AF increased by 27% by each year of increase in disease duration (P = 0.025). Conclusion: It seems that in patients with CP, the presence of pericardial calcification and the increasing disease duration are associated with a higher chance of developing AF.     

A 19-year-old female with blue rubber bleb nevus syndrome. Endoscopic laser photocoagulation and surgical resection of gastrointestinal angiomata

A case of a blue rubber bleb nevus syndrome in a 19-year-old female patient with multiple cutaneous and gastrointestinal hemangiomata is described. Recurrent GI bleeding resulted in severe chronic anemia, which was successfully treated by endoscopic laser photocoagulation and surgical resection. Both forms of therapy had to be repeated 4 years later, the patient having been well in the meantime. This combined endoscopic and surgical approach might also improve the survival of patients with severe GI hemorrhage due to blue rubber bleb nevus syndrome.