A 52 year-old male presented with neck pain after undergoing thyroidectomy for a goiter three weeks prior which was complicated by a neck hematoma requiring evacuation. Computed tomography (CT) scan showed a neck hematoma requiring evacuation and he received desmopressin with cessation of bleeding. Coagulation studies were normal. He returned eighteen months later with severe oral mucosal bleeding after a dental procedure and required transfusions with red blood cells, platelets, and fresh frozen plasma (FFP) in addition to desmopressin, Humate-P, aminocaproic acid, and surgical packing. A comprehensive bleeding diathesis workup was normal. He was readmitted six months later due to abdominal pain and distention and found to have massive hepatosplenomegaly on CT. A new coagulopathy workup revealed prolonged INR to 1.5, corrected prothrombin time mixing study, and a low factor VII level (29%), suggesting acquired factor VII deficiency. A transjugular liver biopsy revealed extensive involvement by ALamyloidosis- Kappa type. He then developed a large right retroperitoneal hematoma which required multiple transfusions with FFP, cryoprecipitate, aminocaproic acid, and vitamin K with slight success. Hemorrhage was subsequently stabilized with recombinant factor VIIa administered every four hours which corresponded with correction of factor VII levels and PT and eventual cessation hemorrhage. Acquired factor VII deficiency causing severe coagulopathy was attributed to hepatic amyloidosis ALkappa subtype. We started treatment with bortezomib, dexamethasone, and cyclophosphamide, however, the patient succumbed to uncontrolled hemorrhage. Acquired factor VII deficiency is extremely rare and to our knowledge, this is the only known case of factor VII deficiency secondary to amyloidosis involving the liver.

Multifocal lymphangioendotheliomatosis with thrombocytopenia is a rare disease characterized by multiple cutaneous and gastrointestinal (GI) vascular lesions and thrombocytopenia refractory to platelet and blood cell transfusions. GI bleeding can become life-threatening in this condition. We report a case of multifocal lymphangioendotheliomatosis with thrombocytopenia in a male infant with isolated GI involvement, diagnosed when he was 3 months old. The patient was managed with daily aminocaproic acid, octreotide drip, and corticosteroids for 13 months after diagnosis; he had complete resolution of symptoms by 2 years of age and showed adequate height and gain by 5 years of age. This case adds to the paucity of data in the literature pertaining to the disease's phenotypic variability, long-term clinical course, and management of GI bleeding.

The purpose of this study was to determine if a higher dosing of ε-aminocaproic acid (EACA) is associated with less perioperative blood loss than a lower dose. A total of 74 patients having scoliosis surgery were analyzed. Of the 74 patients, 36 patients received EACA (10 mg/kg/h) and 38 patients received EACA (33 mg/kg/h). After controlling for key variables, an infusion of 33 mg/kg/h of EACA was associated with an increase in intraoperative blood loss of 8.1 ml/kg compared with an infusion of 10 mg/kg/h of EACA. A 33 mg/kg/h intraoperative infusion is associated with higher intraoperative blood loss than an infusion at 10 mg/kg/h.

To develop novel long-acting antidiabetic agents, mycophenolic acid (MPA) was used to modify Xenopus glucagon-like peptide-1 analog (GLP-1) (1) at three Lys residues through a γ-glutamyl linker. Similarly, 6-aminocaproic acid and 12-aminolauric acid with different lengths of fatty chain were used as MPA derivatives which were then conjugated with 1. By using proper protection and deprotection strategies, the synthetic process was completed directly on the resin to minimize the side reactions, and nine MPA-modified 1 derivatives (2a-2i) were obtained. Compounds 2b and 2c, which showed high GLP-1 receptor activation potencies and glucose lowering activities, were selected for further C-terminal modification to improve their stabilities and bioactivities, giving compounds 3a-3d. The receptor activation potencies and hypoglycemic activities of 3a-3d were comparable to that of liraglutide. Physicochemical and in vitro stability tests revealed that MPA conjugation led to enhanced albumin binding abilities as reflected by the improved stabilities of 3a-3d. In particular, at a dose of 25 nmol kg-1, the in vivo antidiabetic and insulinotropic activities of 3d were comparable to those of semaglutide. Finally, long-term administration of 3d achieved beneficial effects on glucose tolerance normalization and glycated hemoglobin (HbA1c) lowering, and no hepatotoxicity was observed. In conclusion, this research demonstrated that MPA derivatization was a practical way to develop long-acting antidiabetic peptides.

Objective To observe the effect of Gui Zhi Fu Ling Jiao Nang (GZFLJN) on the expressions of alpha smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) in uterine vascular smooth muscle cells (VSMC) of rat models with an intrauterine device (IUD) and to determine the thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α) levels in peripheral blood. Methods Female Wistar rats were randomly divided into four groups:normal group (n=16,with normal breed without treatment),model group (n=18,drenching 0.9% normal saline after modeling of IUD),GZFLJN group (n=18),and aminocaproic acid tablets group (n=17). Immunohistochemical SP method was used to detect the expressions of α-SMA and PCNA in uterine VSMC.ELISA was served to detect the levels of TXB2 and 6-keto-PGF1α in peripheral blood. Results The positive rate of α-SMA were (50.89±9.41)%,(26.93±6.80)%,(48.92±6.80)%,and (34.63±7.26)%,respectively,in normal group,model group,GZFLJN group,and aminocaproic acid tablets group;obviously,it was significantly higher in normal group (t=14.43,P=0.00) and GZFLJN group (t=11.37,P=0.00) than that in model group and it was significantly lower in aminocaproic acid tablets group than in normal group (t=9.96,P=0.00) and GZFLJN group (t=8.23,P=0.00). The positive rate of PCNA were (25.66±7.24)%,(61.26±9.98)%,(28.36±9.17)%,and (50.23±8.71)%,respectively,in these four groups;obviously,it was significantly lower in the normal group (t=20.86,P=0.00) and GZFLJN group (t=19.12,P=0.00) than in model group and it was significantly higher in aminocaproic acid tablets group than in normal group (t=17.82,P=0.00) and GZFLJN group (t=16.05,P=0.00). Serum TXB2 level in these four groups were (445.86±24.43),(508.78±12.42),(448.11±9.63),and (498.11±13.63)ng/L;obviously,it was significantly higher in model group than in normal group (t=16.55,P=0.00) and aminocaproic acid tablets group (t=-4.12,P=0.00) and it was significantly lower in GZFLJN group than in model group (t=-15.23,P=0.00) and aminocaproic acid tablets group (t=-12.08,P=0.00). Serum 6-keto-PGF1α level in these four groups were (23.17±1.93),(18.09±0.93),(22.70±1.61),and (20.70±1.41)ng/L,respectively;obviously,it was significantly lower in model group than in normal group (t=-13.98,P=0.00) and aminocaproic acid tablets group (t=5.26,P=0.00) and it was significantly higher in GZFLJN group than in model group (t=11.43,P=0.00) and aminocaproic acid tablets group (t=8.76,P=0.00). Conclusion GZFLJN can regulate the expressions of α-SMA and PCNA of VSMC in the endometrium of IUD rats and the concentrations of TXB2 and 6-keto-PGF1α in the serum.

Indospicine, a non-proteinogenic analogue of arginine, occurs only in Indigofera plant species and accumulates in the tissues of animals grazing on Indigofera. Canine deaths have resulted from the consumption of indospicine-contaminated meat but only limited information is available regarding indospicine toxicity in humans. In this study three human cell lines, Caco-2 (colorectal adenocarcinoma), HT29-MTX-E12 (colorectal adenocarcinoma) and HepG2 (hepatocellular carcinoma), were used to investigate the cytotoxicity of indospicine and its metabolite 2-aminopimelic acid in comparison to arginine. Indospicine and 2-aminopimelic acid were more cytotoxic than arginine, displaying the highest toxicity in HepG2 liver cells. Intestinal transport in vitro also revealed a 2-fold higher transport rate of indospicine compared to arginine. The sensitivity of HepG2 cells to indospicine is consistent with observed canine hepatotoxicity, and considering the higher in vitro transport of indospicine across an intestinal barrier, it is possible that similar ill effects could be seen in humans consuming contaminated meat.