Modification of hyperacute canine renal homograft and pig-to-dog heterograft rejection by the intra-arterial infusion of citrate

Hyperacute rejection was studied in seven presensitized canine recipients of renal homografts and in 22 canine recipients of pig kidneys. Under both experimental circumstances, untreated animals rejected the grafts within a few minutes. With the intra-arterial infusion of sodium citrate, hyperacute heterograft rejection was forestalled for the duration of therapy, and with homografts the benefit outlasted treatment by many hours. The protection of heterografts was not due solely to anticoagulation by the citrate, since heparin in large doses did not accomplish the same thing. A contributory factor may have been complement inhibition since removal of complement by the grafts was greatly reduced in the citrate-treated animals. © 1971

International Veterinary Epilepsy Task Force recommendations for a veterinary epilepsy-specific MRI protocol

Epilepsy is one of the most common chronic neurological diseases in veterinary practice. Magnetic resonance imaging (MRI) is regarded as an important diagnostic test to reach the diagnosis of idiopathic epilepsy. However, given that the diagnosis requires the exclusion of other differentials for seizures, the parameters for MRI examination should allow the detection of subtle lesions which may not be obvious with existing techniques. In addition, there are several differentials for idiopathic epilepsy in humans, for example some focal cortical dysplasias, which may only apparent with special sequences, imaging planes and/or particular techniques used in performing the MRI scan. As a result, there is a need to standardize MRI examination in veterinary patients with techniques that reliably diagnose subtle lesions, identify post-seizure changes, and which will allow for future identification of underlying causes of seizures not yet apparent in the veterinary literature. There is a need for a standardized veterinary epilepsy-specific MRI protocol which will facilitate more detailed examination of areas susceptible to generating and perpetuating seizures, is cost efficient, simple to perform and can be adapted for both low and high field scanners. Standardisation of imaging will improve clinical communication and uniformity of case definition between research studies. A 6–7 sequence epilepsy-specific MRI protocol for veterinary patients is proposed and further advanced MR and functional imaging is reviewed

Systems biology of platelet-vessel wall interactions

Platelets are small, anucleated cells that participate in primary hemostasis by forming a hemostatic plug at the site of a blood vessel's breach, preventing blood loss. However, hemostatic events can lead to excessive thrombosis, resulting in life-threatening strokes, emboli, or infarction. Development of multi-scale models coupling processes at several scales and running predictive model simulations on powerful computer clusters can help interdisciplinary groups of researchers to suggest and test new patient-specific treatment strategies

Investigation into the Role of Tumor-Associated Macrophages in the Antitumor Activity of Doxil

Purpose. Our recent studies show specific localization of long-circulating liposomes (LCL) within the endosomal/lysosomal compartment of tumor-associated macrophages (TAM). Based on this finding, the present study aims to investigate whether clinically applied LCL formulations such as Doxil (LCLencapsulated doxorubicin), have alternative mechanisms of action additionally to direct drug-mediated cytotoxicity towards tumor cells. Methods. The antitumor activity of Doxil was evaluated in B16.F10 melanoma-bearing mice, in the presence and in the absence of TAM. To suppress TAM functions, liposomal clodronate (Lip-CLOD) was injected 24 h before the actual treatment. The effect of Doxil on the levels of angiogenic factors was determined using an angiogenic protein array. As positive control, the same experiments were conducted with LCL-encapsulated prednisolone phosphate (LCL-PLP), a tumor-targeted formulation with known strong anti-angiogenic/anti-inflammatory effects on TAM. Results. Our results show that the antitumor efficacy of Doxil was only partially attributed to the inhibition of TAM-mediated angiogenesis whereas LCL-PLP inhibited tumor growth through strong suppressive effects on pro-angiogenic functions of TAM. As described previously, the main mechanism of Doxil might be a cytotoxic effect on tumor cells. Conclusions. Our findings suggest that the antitumor activity of Doxil does not depend mainly on the presence of functional TAM in tumors

Subacute Sclerosing Panencephalitis in Papua New Guinean Children: The Cost of Continuing Inadequate Measles Vaccine Coverage

Subacute sclerosing panencephalitis (SSPE) is a disabling and usually fatal brain disorder that typically occurs 3–10 years after acute measles infection. Papua New Guinea (PNG) has particularly high rates of SSPE. We report 22 cases of PNG children presenting to the provincial referral hospital in Madang Province who probably contracted acute measles when <12 months of age during a national epidemic in 2002 and who developed SSPE 5–7 years later. Based on these cases, the estimated annual SSPE incidence in Madang province in 2007–2009 was 54/million population aged <20 years. Four sub-districts had an annual incidence >100/million population aged <20 years, the highest rates ever reported. Young PNG children do not respond well to measles vaccine. Because of this, efforts such as supplementary measles immunisation programs should continue in order to reduce the pool of non-immune older people surrounding the youngest and most vulnerable members of PNG communities

Biological mechanism and clinical effect of protein-bound polysaccharide K (KRESTIN®): review of development and future perspectives

The mechanism of action of protein-bound polysaccharide K (PSK; KRESTIN®) involves the following actions: (1) recovery from immunosuppression induced by humoral factors such as transforming growth factor (TGF)-β or as a result of surgery and chemotherapy; (2) activation of antitumor immune responses including maturation of dendritic cells, correction of Th1/Th2 imbalance, and promotion of interleukin-15 production by monocytes; and (3) enhancement of the antitumor effect of chemotherapy by induction of apoptosis and inhibition of metastasis through direct actions on tumor cells. The clinical effectiveness of PSK has been demonstrated for various cancers. In patients with gastric or colorectal cancer, combined use of PSK with postoperative adjuvant chemotherapy prolongs survival, and this effect has been confirmed in multiple meta-analyses. For small-cell lung carcinoma, PSK in conjunction with chemotherapy prolongs the remission period. In addition, PSK has been shown to be effective against various other cancers, reduce the adverse effects of chemotherapy, and improve quality of life. Future studies should examine the effects of PSK under different host immune conditions and tumor properties, elucidate the mechanism of action exhibited in each situation, and identify biomarkers