Charge affects the oral toxicity of poly(amidoamine) dendrimers.

Poly(amidoamine) (PAMAM) dendrimers have been evaluated for the influence of surface functionality and size on the epithelial barrier of the gut with the goal of identifying safe carriers that can be used for oral drug delivery. Limited studies are conducted to date, however, to assess the toxicity of PAMAM dendrimers in vivo when administered by the oral route. The goal of this research was to conduct an oral acute toxicity study of PAMAM dendrimers as a function of size and charge in immune competent CD-1 mice. Maximum tolerated doses (MTD) of PAMAM dendrimers as a function of size and surface functionality were established and clinical signs of toxicity monitored. Results demonstrate that positively charged dendrimers caused more toxicity, whereas their anionic counterparts were tolerated at ten times higher doses. Severe signs of toxicity observed for large (G7) cationic amine- or hydroxyl-terminated dendrimers include hemobilia and spleenomegaly. The MTD for these dendrimers ranged from 30 mg/kg to 200 mg/kg. Anionic G6.5 or smaller molecular weight carboxyl-, amine-, or hydroxyl-terminated dendrimers (G3.5-COOH, G4-NH2, G4-OH) on the other hand were tolerated at doses of up to 500 mg/kg (300 mg/kg in some cases) with minimal or no signs of toxicity. Establishing the MTD of orally delivered PAMAM dendrimers and the influence of surface functionality and size on toxicity aids in the rational design of PAMAM-drug conjugates for oral drug delivery applications.

[Haemobilia in the course of acenocoumarol overdosage in patient with cholelithiasis--case report]. / Hemobilia w przebiegu przedawkowania acenokumarolu u pacjentki z kamica zólciowa--opis przypadku.

Haemobilia is a rare cause of acute upper gastrointestinal bleeding and is often associated with a history of hepatic or biliary tract injury, tumor growth, hepatic artery aneurysm, cholecystitis, or hepatic abscess. We report a case of a 79-year-old women with haemobilia due to acenocoumarol overdosage. She has been, taking 12 mg acenocoumarol by mistake for 5 days before admission because of atrial fibrillation. INR was 20 during an admission. Ultrasonographic evaluation demonstrated hepatomegaly, cholelithiasis, thick sludge in gallbladder represented blood clots and also dilated biliary tract. Cholecystectomy was carried out. The cut section of gall bladder showed stone, haemolysed blood and blood clots. Choledochotomy showed only blood clots within the duct. The treatment lasted long period and patient died because of multiorgan insufficiency in the course of sepsis.

[A case of non-traumatic hemobilia due to warfarin therapy].

Hemobilia is a hemorrhage into the biliary tract that may follow surgical trauma, liver biopsy, aneurysms, extra- or intra-hepatic tumors of the biliary tract, gallstones, and inflammatory lesion of liver, especially helminthic or pyogenic. Sometimes, it is associated with primary liver cancer. An 84 year-old woman was admitted because of continuous right upper quadrant pain 4 days before admission. Physical examination revealed decreased skin turgor, icteric sclerae and severe tenderness on right upper quadrant abdomen. She had no hepatosplenomegaly, and no rebound tenderness. She has been taking warfarin for 3 weeks before admission because of atrial fibrillation. On admission, serum bilirubin and transaminase were elevated. The level of hemoglobin and hematocrit were 11.3 g/dL and 37.4%, respectively. HBsAg was negative, but IgG anti-HBc and anti-HBs were positive and anti-HCV was negative. Parasite skin test and stool ova count demonstrated non-specific findings. Stool occult blood was strongly positive, and prothrombin time was markedly prolonged. According to endoscopic retrograde cholangiopancreatography, common bile duct was dilated, and filled with blood clot but there was no stone in bile tree. After two weeks, serum transaminase, bilirubin, hemoglobin, hematocrit, and CA19-9 were normalized. We report a case of hemobilia, occurring in a patient with continuous warfarin use.

A Case of Non-traumatic Hemobilia due to Warfarin Therapy / 대한소화기학회지

Hemobilia is a hemorrhage into the biliary tract that may follow surgical trauma, liver biopsy, aneurysms, extra- or intra-hepatic tumors of the biliary tract, gallstones, and inflammatory lesion of liver, especially helminthic or pyogenic. Sometimes, it is associated with primary liver cancer. An 84 year-old woman was admitted because of continuous right upper quadrant pain 4 days before admission. Physical examination revealed decreased skin turgor, icteric sclerae and severe tenderness on right upper quadrant abdomen. She had no hepatosplenomegaly, and no rebound tenderness. She has been taking warfarin for 3 weeks before admission because of atrial fibrillation. On admission, serum bilirubin and transaminase were elevated. The level of hemoglobin and hematocrit were 11.3 g/dL and 37.4%, respectively. HBsAg was negative, but IgG anti-HBc and anti-HBs were positive and anti-HCV was negative. Parasite skin test and stool ova count demonstrated non-specific findings. Stool occult blood was strongly positive, and prothrombin time was markedly prolonged. According to endoscopic retrograde cholangiopancreatography, common bile duct was dilated, and filled with blood clot but there was no stone in bile tree. After two weeks, serum transaminase, bilirubin, hemoglobin, hematocrit, and CA19-9 were normalized. We report a case of hemobilia, occurring in a patient with continuous warfarin use.

Antibiotic-induced iatrogenic hemobilia.

A classical triad of clinical signs defines hemobilia: GI bleeding, right upper quadrant abdominal pain, and jaundice. Although there are a number of causes, it is largely described in conjunction with blunt or penetrating liver trauma and as an iatrogenic complication of therapeutic hepatobiliary interventions. We present a case of antibiotic-induced vitamin K deficiency that resulted in hemobilia complicating acalculous cholecystitis.