Intraarterial delivery of virotherapy for glioblastoma

Oncolytic viruses (OVs) have been used in the treatment of cancer, in a focused manner, since the 1990s. These OVs have become popular in the treatment of several cancers but are only now gaining interest in the treatment of glioblastoma (GBM) in recent clinical trials. In this review, the authors discuss the unique applications of intraarterial (IA) delivery of OVs, starting with concepts of OV, how they apply to IA delivery, and concluding with discussion of the current ongoing trials. Several OVs have been used in the treatment of GBM, including specifically several modified adenoviruses. IA delivery of OVs has been performed in the hepatic circulation and is now being studied in the cerebral circulation to help enhance delivery and specificity. There are some interesting synergies with immunotherapy and IA delivery of OVs. Some of the shortcomings are discussed, specifically the systemic response to OVs and feasibility of treatment. Future studies can be performed in the preclinical setting to identify the ideal candidates for translation into clinical trials, as well as the nuances of this novel delivery method.

Hepatic Microhaemocirculation Dynamics in Experimental Extrahepatic Cholestasis

Aim. Investigation of hepatic microhaemocirculation effects in experimental extrahepatic cholestasis.Materials and Methods. Experiments were carried out with a mixed group of 48 white mongrel male rats. Extrahepatic cholestasis was modelled in rats with via the ligation of common bile duct.Results. Animals with ligated common bile duct showed abnormalities in peripheral hepatic circulation manifested by a complex of intravascular, vascular and paravascular changes, hepatic angioarchitectonics disturbance, a marked growth of parenchymal dystrophic lesions in the form of post-haemorrhagic foci. The disturbance was pronounced towards a virtual degradation of hepatic parenchyma and the growth of “numb” zones with ceased circulation.Conclusion. The trials revealed microcirculatory changes in the liver associated with rheological disturbance of blood and, subsequently, the toxic impact of failed metabolism.

Comprehensive MRI assessment of the cardiovascular responses to food ingestion in Fontan physiology

Novel data on cardiovascular physiology in response to a meal in Fontan patients are presented. Using a previously validated dynamic MRI protocol, we demonstrated that the usual increase in cardiac output and the dilation of the superior mesenteric artery are preserved in clinically well Fontan patients. In contrast, vasoconstriction of the legs may have prevented redistribution of blood flow from this region in response to the meal. This may also affect responses to other types of stress. Celiac vasodilation was also absent in Fontan patients. This may be due to abnormal hepatic circulation. The proposed protocol may be used to study Fontan complications secondary to abnormal regional hemodynamics.

Dietary fibre, functions by modulating the entero-hepatic circulation

Dietary Fibre (DF) is not an essential component of the diet but a modulator of the absorption and colonic metabolism of nutrients and xenobiotics along the small and large intestine. In the colon DF stimulates the bacterial flora, bacterial mass and metabolism, thereby influencing the entero-hepatic circulation (EHC) and faecal output. This modulation is dependent upon the amount and physical state of DF intake.