The interaction between oxytocin and heparin

Oxytocin (OXT) is a small cyclic peptide that is administered to pregnant women to induce birth in cases where labour is prolonged. It has previously been observed that patients taking a low molecular weight heparin, dalteparin (DAL), and then prescribed, OXT experienced a swifter labour compared to women given OXT alone. Herein are described the interactions between OXT and a number of heparin-based oligosaccharides; DAL; fondaparinux (FP), which is a synthetic heparin oligosaccharide that represents the predominant antithrombin binding-site, and a family of chemically-derived heparin hexasaccharides. The latter oligosaccharides were chosen as they represent sequences found within the polysaccharide dalteparin. Furthermore, the carbohydrate chemical space was investigated by comparing the interaction between OXT and four chemically derivatived heparin hexasaccharides; I_2S-A^6S_NS (DP6), I_2OH-A^6S_NS (DP6-2OH, de-2-O-sulfated hexasaccharide), I_2S-A^6OH_NS (DP6-6OH, de-6-O-sulfated hexasaccharide) and I_2S-A^6S_NAc (DP6-NAc, de-N-sulfated hexasaccharide). The interactions between the peptide and oligosaccharides were studied using a series of ¹³C–¹H and ¹⁵N–¹H HSQC NMR experiments, at a range of temperatures. This approach allowed the binding epitopes of the peptide and oligosaccharides to be identified, highlighting that 6-O- and N-sulfation substituent groups of heparin are important for the interaction between the peptide and carbohydrate. This is an important observation as de-N-sulfation is a traditional method for decreasing the anticoagulation properties of heparin. Furthermore, low temperature experiments of the OXT : FP complex indicate that hydrogen-bonding is very important for the interaction between the peptide and oligosaccharide.

Heparin interacts with the nonapeptide oxytocin, the binding region preferentially involves the 6-O- and N-sulfates of glucosamine.     

Correction to: Positron Emission Tomographic Imaging of Tumor Cell Death Using Zirconium-89-Labeled APOMAB® Following Cisplatin Chemotherapy in Lung and Ovarian Cancer Xenograft Models

Molecular Imaging and Biology -     

A protocol system for testing biohazardous materials in an impact biomechanics research facility.

This article presents a protocol system, comprised of a review process and a series of checklists, that was developed for testing cadaveric tissue in an impact biomechanics research facility. The use of cadaveric tissue may expose personnel to bloodborne pathogens including HIV and hepatitis B, which have been shown to remain virulent in a cadaver for several weeks after death. To minimize exposure risks, the protocol system presented emphasizes initial blood screening to keep infectious tissue from entering the laboratory, and adopts universal precautions to prevent exposure by treating all tissue as though it were infected. All lab employees must read, sign, and demonstrate proficiency in the protocol. Well-developed test procedures for the handling of biohazardous materials along with an annual individual protocol review have proven effective for the past 6 years in minimizing exposure risks.     

Comparison of characteristics of patients and treatment outcome for pulmonary non-tuberculous mycobacterial infection and pulmonary tuberculosis.

BACKGROUND: Patients with non-tuberculous mycobacteria are usually started on conventional antituberculous triple therapy once acid fast bacilli are detected, before the exact type of mycobacteria has been identified. The ability to identify the characteristics of patients with tuberculous and non-tuberculous mycobacteria may be helpful in identifying before treatment those patients more likely to have non-tuberculous infection. METHODS: A retrospective study was conducted of all patients in one unit in whom non-tuberculous mycobacteria were identified in sputum or bronchoalveolar washings in the period 1987-93. The pattern of drug resistance was determined from laboratory records, and all case notes and chest radiographs were reviewed to identify the underlying disease and treatment outcome. All cases were compared with a matched control group of patients with culture positive Mycobacterium tuberculosis diagnosed during the same period. RESULTS: In the period studied there were 70 non-tuberculous and 221 tuberculous isolates. The non-tuberculous bacteria were typed as follows: M xenopi 23 (33%), M kansasii 19 (27%), M fortuitum 14 (20%), others 14 (20%). Of those with non-tuberculous mycobacteria, 83% were white subjects compared with 47% for tuberculosis. Patients with non-tuberculous mycobacteria were older than those with tuberculosis. Pre-existing lung disease or AIDS was present in 81% of patients with non-tuberculous mycobacteria and in 17% of patients with tuberculosis. Sensitivity to rifampicin and ethambutol was seen in 95% of M xenopi and 96% of M kansasii isolates. Relapse occurred in 60% of cases infected with M xenopi, 20% infected with M kansasii, and in 7% of cases with tuberculosis. CONCLUSIONS: In the population studied non-tuberculous mycobacteria occurred most frequently in elderly white subjects with pre-existing lung disease. If mycobacteria are detected in this group, consideration should be given to the possibility of non-tuberculous infection before embarking on treatment. A combination containing rifampicin and ethambutol is effective. The relapse rate for infection with M xenopi is high and prospective studies of the effect of the above combination of antituberculosis drugs are needed.