Proton pump inhibitors for the treatment of cancer in companion animals

The treatment of cancer presents a clinical challenge both in human and veterinary medicine. Chemotherapy protocols require the use of toxic drugs that are not always specific, do not selectively target cancerous cells thus resulting in many side effects. A recent therapeutic approach takes advantage of the altered acidity of the tumour microenvironment by using proton pump inhibitors (PPIs) to block the hydrogen transport out of the cell. The alteration of the extracellular pH kills tumour cells, reverses drug resistance, and reduces cancer metastasis. Human clinical trials have prompted to consider this as a viable and safe option for the treatment of cancer in companion animals. Preliminary animal studies suggest that the same positive outcome could be achievable. The purpose of this review is to support investigations into the use of PPIs for cancer treatment cancer in companion animals by considering the evidence available in both human and veterinary medicine

Determination of factor IX allotypes for carrier identification in haemophilia B

The existence of two genetic variants (allotypes) of normal human factor IX is used for carrier detection in three families with severe and one with mild haemophilia B. By analysis of IX:Ag with two different monoclonal antibodies in 93 members of the families, allelic assignment is shown to be a complement in carrier diagnosis to genotypic DNA studies. Allelic assignment makes possible a reliable diagnosis based on phenotypic studies, though its usefulness is limited due to ethnic variation in allelic frequency. Determination of factor IX allotypes should be useful for carrier detection in any Swedish families with haemophilia B

Intraplatelet cyclic 3'-5' guanosine monophosphate is related to serum cholesterol

Nitric oxide (NO) exerts its vasodilator and antiaggregatory effects through activation of soluble guanylate cyclase and the consequent increase in the concentration of cGMP in target cells. We conducted this study in order to evaluate relationships between intraplatelet cGMP levels and risk factors for atherosclerosis in middle aged subjects. Intraplatelet cGMP was determined by radioimmunoassay and related to age, BMI, blood pressure, antihypertensive treatment, total, LDL and HDL cholesterol, triglycerides, blood glucose, HbA1c, smoking habit and intimal thickness of the common carotid artery in 265 subjects participating in a health survey (age 59 ± 6 years, range 48-68 years, 121 females, 144 males). Intraplatelet cGMP concentration was inversely correlated with total serum cholesterol (r = -0.18; p < 0.01) and HDL cholesterol (r = -0.14, p < 0.05) as well as with platelet count (r = -0.29; p < 0.001). When platelet count was adjusted for, only the correlation between total serum cholesterol and cGMP remained significant. No significant correlations could be demonstrated between intraplatelet cGMP levels and measurable parameters of atherosclerosis. Lower levels of the vasodilating and antiaggregating mediator cGMP in platelets are related to higher levels of serum total cholesterol. These results favour the hypothesis of a relationship between lipid levels and NO associated vasodilator and antiaggregating fuction in atherosclerosis

Polymorphism of normal factor IX detected by mouse monoclonal antibodies.

Hemophilia B is an X-chromosomal recessive disease due to deficiency of coagulation factor IX. Three monoclonal antibodies against factor IX were prepared and used to develop immunoradiometric assays (IRMAs) of factor IX antigen (IX-Ag). IX-Ag was measured in 65 normal individuals with one IRMA based on polyclonal anti-IX antibodies and two IRMAs based on three monoclonal anti-IX antibodies. One of the monoclonal antibodies differed in specificity since it neutralized less than 50% of the clotting activity of factor IX (IX-C), whereas the other two monoclonal antibodies neutralized 80-95%. When the former antibody was used as the solid phase in IRMA, two groups of normal individuals were distinguished: group A with measurable IX-Ag, and group B without demonstrable IX-Ag. There were no differences between the groups either in IX-C or in IX-Ag measured with polyclonal antibodies. A subgroup comprising only women could be distinguished in group A, in whom intermediate IX-Ag concentrations were found. Family studies showed the group B variant of normal factor IX to be transmitted according to the pattern of X-linked recessive inheritance. The allelic frequency of group A was 0.66, and that of group B was 0.34