Childhood pheochromocytoma crisis complicated with brain stem infarction: A case report.

RATIONALE: Pheochromocytoma crises are very rarely seen in children. In this report, we present a case of the death related to occult pheochromocytoma crisis combined cerebral infarction. PATIENT CONCERNS: A 5-year-old boy has a 1-month history of polydipsia, polyuria, sweating, and weight loss of 2.5 kg. He was admitted to our hospital because of 1 week of anorexia, 2 days of vomiting, and 12 hours of convulsions and confusion. Magnetic resonance imaging of the brain and cervical spinal cord showed abnormal signals in the left parie-occipital lobe, medulla oblongata till C7 cervical vertebrae. DIAGNOSES: Based on patient's complaints and clinical appearance, provisional diagnosis of pheochromocytoma crisis complicated brainstem infarction was considered. INTERVENTIONS: Tracheal intubation, volume expansion, continuous infusion of dobutamine, and sedation reduce intracranial pressure. Chest compression was performed when the child suddenly developed sobbing respiration. OUTCOMES: The patient was dead. Congenital metabolic defects screening suggested mild ketonuria. Trio whole exon sequencing revealed a synonymous mutation of von Hippel-Lindau syndrome c.414 A > G in the decedent. Autopsy revealed pheochromocytoma, acute myocarditis, liquefaction necrosis of the medulla oblongata cerebral edema, and congestion. LESSONS: Early clinical symptoms of pheochromocytoma in children are not typical. It may induce serious complications and develop into a pheochromocytoma crisis and cause death without proper treatment.

Deltonin inhibits angiogenesis by regulating VEGFR2 and subsequent signaling pathways in endothelial cells.

Deltonin is a steroidal saponin which could suppress tumor growth through suppressing angiogenesis, but the mechanisms have not been directly elucidated yet. In the present study, we showed that deltonin inhibited the proliferation of primary cultured human umbilical vein endothelial cells (HUVECs) in vitro; notably, it could significantly inhibit HUVECs migration, invasion, and tube formation, which are indispensable progresses of angiogenesis. We further demonstrated that deltonin could inhibit VEGF-induced blood vessel formation in vivo. What is more, we found that deltonin blocked VEGF triggered phosphorylation of key intracellular angiogenic molecules, such as VEGFR2, Src family kinase, focal adhesion kinase (FAK), extracellular signal-related kinase (Erk1/2) and AKT kinase, accompanied with the increase of phosphorylated P38MAPK. Taken together, the present study demonstrates that deltonin inhibits angiogenesis through regulating VEGFR2 signaling pathway as well as AKT/MAPK signaling pathways in endothelial cells.

Cytotoxicity and apoptosis-inducing effect of steroidal saponins from Dioscorea zingiberensis Wright against cancer cells.

Steroidal saponins from Dioscorea zingiberensis Wright (DZW) have shown cytotoxic activity in cancer cells. In this study, we isolated and identified seven steroidal saponins from the rhizomes of DZW: diosgenin, trillin, diosgenin diglucoside, deltonin, zingiberensis saponin (ZS), protodeltonin and parvifloside. Our results showed that these seven compounds inhibited the proliferation of a panel of established human and murine cancer cell lines in vitro. ZS had more cytotoxic effect than the other saponins, even close to doxorubicin on the murine colon carcinoma cell line C26. The proliferation inhibitory effect of ZS was associated with its apoptosis-inducing effect by activation of caspase-3 and caspase-9 and specific proteolytic cleavage of poly (ADP-ribose) polymerase. Exposure of C26 to ZS also resulted in Bax upregulation and Bcl-2 downregulation. In conclusion, the findings of this study demonstrated that ZS is an effective natural agent for cancer therapy, which may be mediated, in part, by induction of apoptosis, and DZW's potential as an anticancer agent is worth being further investigated.

Anti-thrombotic activity and chemical characterization of steroidal saponins from Dioscorea zingiberensis C.H. Wright.

Steroidal saponins have long attracted scientific attention, due to their structural diversity and significant biological activities. Total steroidal saponins (TSS) extracted from the rhizomes of Dioscorea zingiberensis C.H. Wright (DZW) constitute an effective treatment for cardiovascular disease. However, the active constituents contained in DZW rhizomes and their pharmacological properties are not fully understood. The aim of this work is to determine and quantify the active constituents in DZW rhizomes using fingerprint technique, and evaluate its anti-thrombotic activity using inferior vena cava ligation thrombosis rat model and pulmonary thrombosis mice model after being gavaged with TSS for 1 or 2weeks. In the study, a chemical fingerprint method was firstly established and validated to quantify and standardize TSS from DZW rhizomes including parvifloside, protodeltonin, protodioscin, protogracillin, zingiberensis saponin, deltonin, dioscin and trillin. TSS extracted from DZW rhizomes were showed to have the inhibitions on platelet aggregation (PAG) and thrombosis, and prolong activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT) in a dose-dependent manner in rats. TSS also prolonged the bleeding time and clotting time in a dose-dependent manner in mice. The results indicate that TSS could inhibit thrombosis by both improving the anticoagulation activity and inhibiting PAG action, suggesting that TSS from DZW rhizomes have the potential to reduce the risk of cardiovascular diseases by anti-thrombotic action.