Hemolytic activity of 4-(1H-benzimidazol-1-ylmethyl)-and 4-(2-methyl-1H-benzimidazol-1-ylmethyl)phenols and their glycosides

4-(1H-Benzimidazol-1-ylmethyl)-and 4-(2-methyl-1H-benzimidazol-1-ylmethyl)phenyl-β-D-glucopyranosides have been synthesized by glycosylation of the corresponding phenols. The hemolytic activity of the synthesized compounds was studied on whole venous human donor blood at concentrations of 100, 200, and 300 μg/mL. It was established that the glycosides exhibit high biological activity and enter erythrocytes faster than do the initial phenols, which suggests that they are promising for the development of new drugs. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 12, pp. 16–17, December, 2007.     

In vitro physiological evidence of enhanced antioxidant and neuroprotective action of 2,3-dihydromelatonin, a melatonin analogue.

As the capacity of the endogenous antioxidative system is limited, pharmacological treatment with antioxidants may help to protect neuronal tissue against increased amount of reactive oxygen species produced during oxidative stress. We attempted to improve resistance of rat hippocampal slices exposed to ischaemia in vitro (hypoxia (HYP) accompanied with decreased glucose concentration followed by reoxygenation (ROX)) and thus to diminish the impairment of synaptic transmission after HYP/ROX. We compared the protective features of the melatonin analogue 2,3-dihydromelatonin (2,3-DHM) with melatonin itself. In preliminary experiments, the compound 2,3-DHM compared to melatonin revealed enhanced antilipoperoxidation action in rat brain homogenates exposed to Fe/ascorbate system (-logIC(50) = 4.76 +/- 0.01 versus -logIC(50) = 2.51 +/- 0.02, respectively). In this study, 2,3-DHM (from 0.3 to 10 micromol l(-1)) applied at 30 min before the beginning of HYP and remaining all over the 6-min HYP as well as 20-min ROX, exerted a protective effect demonstrated by improvement of the population spike amplitude (PoS) recovery during ROX, with the maximum effect at 3 micromol l(-1). In accordance with this, the ratio of irreversibly damaged slices after HYP/ROX was decreased in the groups treated with 2,3-DHM. Moreover, a significant delay of PoS decay during HYP (expressed as half time, t(0.5)) was revealed at 2,3-DHM concentration 1 and 3 micromol l(-1)). An equipotent effect of melatonin and 2,3-DHM was achieved by a 100-times lower concentration of the latter (0.3 and 1 micromol l(-1)) compared to that of melatonin (30 and 100 micromol l(-1)). Further, compared to the highest effect of 2,3-DHM in the concentration 3 micromol l(-1) on the percentage of irreversibly damaged slices (only 20%), melatonin did not exert such pronounced effect, either in the concentration 30 or 100 micromol l(-1) (67 and 50%, respectively). We conclude that hydrogenation of the melatonin molecule significantly improved its antihypoxic effect in our model of rat hippocampal slices exposed to ischaemic conditions in vitro, similarly as it enhanced the antilipoperoxidation action of 2,3-DHM in our previous studies. These findings suggest that 2,3-DHM deserves more attention concerning its neuroprotective effect in oxidative stress-associated tissue damage.     

Regeneration of skeletal muscles and state of thymus in gamma-irradiated rats under laser therapy of the area of muscle trauma.

The gamma-irradiation of adult rats with a semi-lethal dose (6 Gy) suppressed the posttraumatic regeneration of skeletal muscles and brought about considerable destructive changes in the thymus. The effect of He-Ne laser radiation at a total dose 4.5-5.4 J/cm2 at each operated leg in irradiated rats stimulated the regenerative capacity of skeletal muscle tissue, the healing of skin-muscle wound, and the processes of postradiation recovery in thymus cells (a decrease of chromosome aberrations). The histological structure of regenerates had more muscle pattern. At the same time, the positive dynamics of regenerative processes in muscles was achieved by an increased functional load on the thymus. To stimulate the regeneration of irradiated muscles on the background of a more moderate load on the thymus, the prolonged period of laser therapy and fragmentary distribution of laser exposures during muscle regeneration were preferable. Wound healing improved visibly. Nor formation of chronic radiation ulcers on operated shins was observed.     

Occult metastatic neck disease: detection with US and US-guided fine-needle aspiration cytology

The authors performed a prospective study of the value of ultrasonography (US) and US-guided fine-needle aspiration cytology (FNAC) for assessment of N0 lesions in the neck. Preoperative US was performed in 107 patients with squamous cell carcinoma of the head and neck, who underwent 132 elective neck dissections. During the US examination of the last 54 patients, who underwent 70 elective neck dissections, US-guided FNAC was performed. US alone was found to be an unreliable method for detecting occult lymph node metastasis; the accuracy never exceeded 70% (93 of 132), with a sensitivity of 60% (32 of 53) and a specificity of 77% (61 of 79). In contrast, US-guided FNAC had an accuracy of 89% (62 of 70), a sensitivity of 76% (25 of 33), and a specificity of 100% (37 of 37). Because of the high sensitivity and specificity of US-guided FNAC for the assessment of the N0 neck, this modality may play an important role in directing treatment of these patients in the future.     

P63Stem Cell and Immunotherapy Services, NHS Blood and Transplant, Birmingham, UK

Over 20 years ago, the Birmingham Blood Centre established a facility for the cryopreservation of bone marrow (BM) for patients in the West Midlands suffering from haematopoietic disorders and for whom a bone marrow transplant was indicated. Today, the use of mobilised peripheral blood (PBSC) has overtaken bone marrow as the source of stem cells for transplantation and the numbers of patients benefitting and the diversity of conditions being treated has increased enormously. Allogeneic transplants, using stem cells from healthy donors, have become increasingly successful as a result of an improving understanding of the complexities of the HLA histocompatibility system. Additionally umbilical cord blood (HUC), which in the 1980s was recognised as a source of stem cells, can now be collected and used for transplantation. As scientific knowledge and the clinical management of patients has advanced, so too have laboratory methods for manipulating cell products to enrich or deplete certain cell populations (e.g. by CD34+cell selection) in order to minimise potentially fatal graft-versus-host disease (GVHD) or to eliminate tumour cells in the case of autologous patients. Donor lymphocytes (DLI) may also be collected and used to aid a graft-versus-leukaemia (GVL) effect. The laboratory is currently developing protocols for immunotherapy using virus-specific T cells which can be prepared and infused to combat potentially fatal CMV disease post-transplant. Clinical trials of vaccines employing tumour specific dendritic cells for treating patients with hepatocellular carcinoma (HCC) and metastatic melanoma (MM), which do not respond to conventional treatments, are also underway. The advances and expansion in the Stem Cell and Immunotherapy (SCI) service in Birmingham over the last 10 year period are reflected in the table below:
 

     

Mucosal features and granulocyte–monocyte-apheresis in steroid-dependent/refractory ulcerative colitis

BACKGROUND: Mucosa-infiltrated granulocyte neutrophils are an early characteristic of inflammation and the main histological feature of active ulcerative colitis. Mucosal healing has recently been indicated as an important tool in the evaluation of response to treatment. While several studies have stressed the efficacy of granulocyte-monocyte-apheresis in inducing clinical remission in active ulcerative colitis, few data are available on mucosal features. AIM: Aim of this study was to assess the effects of granulocyte-monocyte-apheresis on clinical and mucosal features in patients with ulcerative colitis, dependent upon or refractory to steroids. MATERIAL AND METHODS: From April 2004 to April 2005, 12 patients (5 females, 7 males, mean age 49 years, range 33-71 years), with mild-moderate ulcerative colitis (six left colitis, six pancolitis) dependent/refractory upon steroids were enrolled. Each patient was treated for a 5-week period with five cycles of granulocyte-monocyte-apheresis. Patients were evaluated at baseline and 1 week after the last apheresis by means of Global Physician Assessment, quality of life features, laboratory tests (erythrocyte sedimentation rate, CRP, full blood count, faecal calprotectine), endoscopy and histology. RESULTS: At week 6 of follow-up, complete mucosal healing was observed in 3 out of 12 patients, partial mucosal healing in 8 patients and no change in 1 patient. Clinical response was complete in 8 out of 12 patients. CONCLUSIONS: These data suggest that granulocyte-monocyte-apheresis induces an improvement both in clinical and mucosal lesions in steroid-dependent/refractory ulcerative colitis. Of note, the reduction in granulocyte infiltration and the improvement in mucosal lesions are accompanied by a reduction in faecal calprotectine.