Gastroesophageal reflux disease is the most common malady of the esophagus, affecting 7% of the United States population. Histological assessment demonstrates classic inflammatory mechanisms including selective leukocyte recruitment and hemorrhage, suggesting a prominent role for the microvasculature. We isolated and characterized human esophageal microvascular endothelial cells (EC) (HEMEC), examined inflammatory activation in response to cytokines, LPS, and acidic pH exposure, and identified signaling pathways that underlie activation. HEMEC displayed characteristic morphological and phenotypic features including acetylated LDL uptake. TNF-alpha/LPS activation of HEMEC resulted in upregulation of the cell adhesion molecules (CAM) ICAM-1, VCAM-1, E-selectin, and mucosal addressin CAM-1 (MAdCAM-1), increased IL-8 production, and enhanced leukocyte binding. Both acid and TNF-alpha/LPS activation lead to activation of SAPK/JNK in HEMEC that was linked to VCAM-1 expression and U-937 leukocyte adhesion. Expression of constitutive inducible nitric oxide synthase in HEMEC was in marked contrast to intestinal microvascular endothelial cells. In this study, we demonstrate that HEMECs are phenotypically and functionally distinct from lower gut-derived endothelial cells and will facilitate understanding of inflammatory mechanisms in esophageal inflammation.
Pioglitazone (PZ) an anti-hyperglycemic agent is used in the treatment of type 2 diabetes. The aim of this study was to design PZ-loaded nanostructured lipid carriers (NLC) to investigate the bioavailability improvement by transdermal delivery. PZ NLCs were prepared using highpressure homogenization followed by ultrasonication. The NLCs were evaluated for particle size analysis, drug loading, ex vivo skin transport studies and in vivo bioactivity study. The prepared NLCs had a mean size of 166.05 nm and drug loading of 10.41% with flux value of 47.36 mg/cm 2 /h. The entrapment of PZ is 470% in the NLCs with enhancement ratio of 3.2 times. The in vivo pharmacokinetic study showed 2.17 times enhancement in bioavailability study and pharmacodynamics study showed that PZ NLC-based transdermal therapeutic system (PNLG-TTS) lowers blood sugar level in a sustained pattern for a prolonged period of time as compared to Piosys tablet (marketed). The shelf life of the optimized formulation was found to be 1.83 years. These results clearly provide a lead that above NLCs-based TTS is potential controlled release formulation for PZ and could be a promising drug delivery system for the treatment of diabetes.
We report a case of 14-year-old male, who presented to us with complaints of severe pain in abdomen, vomiting, and inability to pass feces and flatus. He was diagnosed as a case of peritonitis after careful history, examination, and investigations. The exact cause of peritonitis was not known. Exploratory laparotomy was done, and it was found that there was perforation of the right hepatic duct about 1 cm proximal to its confluence with the left hepatic duct. Perforation was closed around the T-tube. Postoperative T-tube cholangiogram was done after 3 weeks which confirmed the free passage of dye into the duodenum, and there was no leakage of dye. T-Tube was removed 4 weeks after the operation, and the patient was discharged in satisfactory condition. Postoperative follow-up was done for 3 months, and it was uneventful.
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