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.     

Pulmonary arterio-venous fistulae in hepatic cirrhosis

Cyanosis, clubbing, and arterial oxygen desaturation may occur in patients with liver disease, and are attributed to the presence of pulmonary or peripheral arterio-venous shunting. Cardiac catheterisation and angiocardiography in a patient with a normal heart did not demonstrate the presence of abnormal arterio-venous anastomoses. Pulmonary shunting was proved when intravenous technetium-labelled macroaggregated albumin, normally held up in capillary networks, was passed quickly through the lungs and immediately detected in high systemic blood flow organs. The opening of peripheral and pulmonary anastomoses in patients with liver disease may be owing to the presence of a vasodilatory substance such as ferritin, which was found to be abnormally increased in the patient's blood.     

Common allergens in shoe dermatitis: our experience in Lahore,Pakistan

BACKGROUND: Shoe dermatitis is a form of contact dermatitis resulting from exposure to shoes. Different chemicals, in conjunction with a hot and humid environment within the shoe, give rise to allergic or irritant dermatitis. Allergic shoe dermatitis is commonly caused by constituents of rubber, leather, adhesives, and rarely by linings and dyes. AIM: To determine the frequency of various allergens in shoe dermatitis in our patients. METHODS: One hundred and nine patients suspected of having contact dermatitis due to shoe allergens were included. All patients were patch tested with the Shoe series and European Standard series. Patches were applied on the upper back and removed after 48 h. Results were read at 48, 72, and 120 h and interpreted according to International Contact Dermatitis Research Group (ICDRG) criteria. RESULTS: Of the 119 patients, 87 (73%) reacted positively to various allergens, 48% of whom showed polysensitivity. Glues (33.6%), particularly para-tert-butylphenol formaldehyde resin (PTBP-FR) (26.9%), were the leading cause of shoe dermatitis. Other allergens were leather chemicals (26.4%), potassium dichromate (16.18%), rubber allergens (7.6%), and dyes (7.6%). Shoe scrapings tested positive in 26.3% of patients. Other common allergens were nickel sulfate (22.7%), neomycin sulfate (10.1%), and cobalt chloride (8.4%). CONCLUSIONS: Considering the diversity of allergens, all patients presenting with shoe dermatitis should be patch tested with the Shoe series and a standard series to determine the etiologic allergens.     

SU5416 delays wound healing through inhibition of TGF-beta 1 activation

Angiogenesis, development of new blood vessels, is essential for wound healing and tumor growth. A potentially important side effect of anti-angiogenic therapy can be delayed wound healing. In this study we address this issue by using a novel in vivo method utilizing fibrin containing dual porous plexiglass chambers (Fibrin Z-Chambers; F-ZC) to investigate wound healing in rats administered with SU5416 (inhibitor of Flk-1 and Flt-1, at 20 mg/kg i.p.). SU5416 treated F-ZCs developed 45% less granulation tissue (p = 0.0076) and showed a 10% reduction in microvessel density (p = 0.0009) than controls treated with drug carrier alone. The granulation tissue showed distinctly decreased collagen deposition (p = 0.0006) in SU5416 treated animals that was associated with 90% reduction in active TGF-beta 1 level. We found that tissue transglutaminase (TG), a cross-linking enzyme involved in TGF-beta 1 activation and matrix stabilization, was inhibited by SU5416. These results suggest that SU5416 delays wound healing by reducing matrix synthesis and stabilization through inhibition of TGF-beta 1 activation. This study was made feasible via the development of a unique method to study anti-angiogenic compounds that provides highly reproducible and quantitative results. Further studies are needed to evaluate in vivo whether anti-angiogenic agents alter wound healing.     

Does leukoaraiosis predict morbidity and mortality?

OBJECTIVE: To determine whether leukoaraiosis predicts morbidity and mortality. BACKGROUND: Gait disturbance and leukoaraiosis both are common in the elderly. Gait disturbance predicts mortality. Leukoaraiosis may be a unifying factor to both gait disturbance and mortality. METHODS: We followed 221 patients prospectively evaluated for severity of neurologic deficits by the National Institutes of Health (NIH) stroke scale and for leukoaraiosis in seven brain regions by CT, graded as absent (n = 119, 54%), mild (in at least one of seven brain regions; n = 54, 24%), or severe (present in all seven brain regions; n = 48, 22%). Pneumonia (n = 27, 12%), falls resulting in fracture requiring hospitalization (n = 7, 3%), and death (n = 38, 17%) were end points. RESULTS: Severe leukoaraiosis predicted death (Cox hazard ratio [HR] = 2.91; 95% CI = 1.5 - 5.6), pneumonia (HR = 5.1; 95% CI = 2.4 - 10.9), death from pneumonia (HR = 8.3; 95% CI = 1.5 - 46), and falls (HR = 6.8; 95% CI = 1.5 - 30). Severe leukoaraiosis predicted a combined end point of death, pneumonia, and falls (HR = 3.5; 95% CI = 2 - 6). Other predictors were NIH stroke scale score, age, smoking, diabetes, gait score, and referral diagnosis of either dementia or Parkinsonism. Severe leukoaraiosis remained a predictor after adjustment for these other factors (HR = 2.2; 95% CI = 1.2 - 3.9), but was borderline after adjusting for gait (HR = 1.96; 95% CI = 0.97 - 3.94; p = 0.061). The combination of severe leukoaraiosis and gait disturbance had the highest risk (HR = 4.4; 95% CI = 2.4 - 7.9). CONCLUSION: Severe leukoaraiosis predicts morbidity and mortality independently of preexisting neurologic deficits. The combination of leukoaraiosis and gait disturbance carries a poor prognosis.