Chinese herbs and warfarin potentiation by 'Danshen'

Drug interactions with warfarin can be dangerous and although common drug interactions are now well recognized those with Chinese herbs are not widely appreciated. 'Danshen' is a herbal medicine often used for various complaints, particularly cardiovascular, in the Chinese community. We report a case of danshen-induced overcoagulation with severe and dangerous abnormalities of clotting in a patient with rheumatic heart disease.     

Skin changes caused by d-penicillamine treatment of arthritis

The clinical, histological and immunopathological details of three cases with a d -penicillamine-induced eruption are presented. The skin changes included (1) pemphigus erythematosus, (2) pemphigus foliaceus, (3) a bizarre localized pruritic papular eruption, the immunopathology of which was characteristic of lupus erythematosus and (4) fragility due to loss of dermal collagen. Circulating IgA was abnormally low in two cases and circulating immune complexes were demonstrated in the third case.     

Novel pharmacogenetic markers for treatment outcome in azathioprine-treated inflammatory bowel disease

Background  Azathioprine (AZA) pharmacogenetics are complex and much studied. Genetic polymorphism in TPMT is known to influence treatment outcome. Xanthine oxidase/dehydrogenase (XDH) and aldehyde oxidase (AO) compete with TPMT to inactivate AZA.
Aim  To assess whether genetic polymorphism in AOX1 , XDH and MOCOS (the product of which activates the essential cofactor for AO and XDH) is associated with AZA treatment outcome in IBD.
Methods  Real-time PCR was conducted for a panel of single nucleotide polymorphism (SNPs) in AOX1, XDH and MOCOS using TaqMan SNP genotyping assays in a prospective cohort of 192 patients receiving AZA for IBD.
Results  Single nucleotide polymorphism AOX1 c.3404A > G (Asn1135Ser, rs55754655) predicted lack of AZA response ( P  = 0.035, OR 2.54, 95%CI 1.06–6.13) and when combined with TPMT activity, this information allowed stratification of a patient's chance of AZA response, ranging from 86% in patients where both markers were favourable to 33% where they were unfavourable ( P  < 0.0001). We also demonstrated a weak protective effect against adverse drug reactions (ADRs) from SNPs XDH c.837C > T ( P  = 0.048, OR 0.23, 95% CI 0.05–1.05) and MOCOS c.2107A > C, ( P  = 0.058 in recessive model, OR 0.64, 95%CI 0.36–1.15), which was stronger where they coincided ( P  = 0.019).
Conclusion  These findings have important implications for clinical practice and our understanding of AZA metabolism.     

Characterisation of the solution conformation of a cyclic RGD peptide analogue by NMR spectroscopy allied with a genetic algorithm approach and constrained molecular dynamics

The solution conformation of a cyclic RGD peptide analogue, cyclo-(S,S)-2-merrcaptobenzoate-arginine-glycine-aspartate -2-mercaptoanilide, has been determined via two independent approaches for the searching of conformational space and identification of conformations consistent with NMR and CD spectroscopic data: (i) the use of a binary genetic algorithm and (ii) a molecular dynamics simulation. Inter-proton distances were obtained via analysis of cross-peak volumes from a two-dimensional ROESY NMR spectroscopy experiment at 600 MHz and were used as constraints for the computational calculations. The mercaptoanilide amide proton resonance chemical shift had a very small temperature coefficient, indicating that this proton was hydrogen-bonded. Circular diehroism data showed that, in solution, the torsion angle about the disulfide bond was negative, consistent with one of the distinct conformations around this bond in the 200 ps molecular dynamics simulation. The backbone conformations of the structures resulting from the two different approaches were very similar.     

Spinal electrical stimulation for intractable angina--long-term clinical outcome and safety

Spinal cord electrical stimulation is an alternative therapyfor patients with chronic pain syndromes including angina. Althoughit has been shown to produce symptomatic relief and reduce ischaemia,doubts remain about its long-term safety. We report here forthe first time the results of a follow-up study over a periodof 62 months, mean 45 months (range 21–62), of 23 patientswho had stimulator units implanted for intractable angina unresponsiveto standard therapy. Symptomatic improvement was good and persistedin the majority with a mean (SD) change of NYHA grade from 3.1(0.8) pre-operatively to 2.0 (0.9) (P<0.01) immediately afteroperation and 2.1 (1.07) at the latest follow-up. GTN consumptionfell markedly. Mean (SEM) treadmill exercise time increasedfrom 407 (45) s with the stimulator off to 499 (46) s with thestimulator on (P<0.01). Forty-eight hour ST segment monitoringin those with bipolar leads showed a reduction of total numberand duration of ischaemic episodes. There were three deaths,none of which were sudden or unexplained and this mortalityrate is acceptable for such a group of patients. Two patientshad a myocardial infarction, which was associated with typicalpain and not masked by the treatment. Complications relatedto earlier lead designs were frequent. This study confirms that spinal electrical stimulation is aneffective and safe form of alternative therapy for the occasionalpatient whose angina is unresponsive to standard therapies.