Efficacy of 3,5-dibromo-L-phenylalanine in rat models of stroke,seizures and sensorimotor gating deficit

Background and purpose:

Abnormal glutamatergic activity is implicated in neurologic and neuropsychiatric disorders. Selective glutamate receptor antagonists were highly effective in animal models of stroke and seizures but failed in further clinical development because of serious side effects, including an almost complete set of symptoms of schizophrenia. Therefore, the novel polyvalent glutamatergic agent 3,5-dibromo-L-phenylalanine (3,5-DBr-L-Phe) was studied in rat models of stroke, seizures and sensorimotor gating deficit.

Experimental approach:

3,5-DBr-L-Phe was administered intraperitoneally as three boluses after intracerebral injection of endothelin-1 (ET-1) adjacent to the middle cerebral artery to cause brain injury (a model of stroke). 3,5-DBr-L-Phe was also given as a single bolus prior to pentylenetetrazole (PTZ) injection to induce seizures or prior to the administration of the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) to cause disruption of prepulse inhibition (PPI) of startle (sensorimotor gating deficit).

Key results:

Brain damage caused by ET-1 was reduced by 52%, which is comparable with the effects of MK-801 in this model as reported by others. 3,5-DBr-L-Phe significantly reduced seizures induced by PTZ without the significant effects on arterial blood pressure and heart rate normally caused by NMDA antagonists. 3,5-DBr-L-Phe prevented the disruption of PPI measured 3 days after the administration of ET-1. 3,5-DBr-L-Phe also eliminated sensorimotor gating deficit caused by MK-801.

Conclusion and implications:

The pharmacological profile of 3,5-DBr-L-Phe might be beneficial not only for developing a therapy for the neurological and cognitive symptoms of stroke and seizures but also for some neuropsychiatric disorders.     

Surface antigenic determinants on human pluripotent and unipotent hematopoietic progenitor cells

RFB-1 is a monoclonal antibody previously shown to react with granulocyte-monocyte progenitors (CFU-GM) and immature lymphoid cells in human bone marrow. RFB-HLA-DR is a monoclonal antibody that reacts with HLA-DR (la-like) antigens. The present study shows that the bone marrow subset reactive with both RFB-1 and RFB-HLA-DR contains all the cells that give rise to mixed hematopoietic colonies (derived from CFU- GEMM; a pluripotent human progenitor cell) as well as to megakaryocytic (megakaryocyte-CFU-derived) and erythropoietic (derived from erythroid burst-forming units, BFU-E) colonies, as shown by fluorescence- activated cell sorting and complement-mediated cytotoxicity. These results indicate that CFU-GEMM, BFU-E, and megakaryocyte-CFU express RFB-1 and la-like antigens. RFB-1 antigen is also expressed on erythroid colony-forming units (CFU-E). RFB-1 and RFB-HLA-DR are useful reagents in the study of hematopoietic stem cells.     

Treatment of children with neurogenic bladder dysfunctions using dynamic nero-electrostimulation(DENS) and M-Cholinolytic therapy

【Objective】 To investigate effects of combined usage of dynamic neuro-electric stimulation(DNES) and M-cholynolytic therapy(oxybutynin) upon manifestations of neurogenic bladder dysfunctions(NBD) in children.【Method】 Urodynamics examination included registration of extemporaneous urinary excretion,urofluometry,and retrograde cytometry in horizontal and vertical position by example of urodynamic system(UDS) ACS 180 Plus(MENFIS BioMed.,USA).In accordance to severity of clinician manifestations,three groups of patients have been defined(27-highest one,49-middle and 51 low levels).Dynamic neuro-electrostimulation(DNES) procedures were conducted using the"DiaDNES-PKM"device(Russian Federation).The children were exposed to juxtaspinal stimulation on S1-S3 level-altogether 10 sessions have been performed.Oxybutynin(driptan) was used in dosage of 2.5 mg per diem.【Result】It was established that combined usage of DNES and oxybutynin in the group with highest severity caused the reduction of manifestations by 3.1 times while separately given DNES and basic therapy were followed by 34.1% and 28.0% reduction correspondently.Meanwhile,DNES and oxybutynin reduced severity in patients with pronounced disturbances by 7.5 times.Combined usage of oxybutynin and DNES in severely manifested NBD increased the effective volume of bladder by 2.3 times.Also significant reduction of both intrabladder pressure(by 48.0%) and compliance of the bladder(by 4.8 times) were detected under condition of combined usage of DNES and oxybutynin.All mentioned indices were modified to less extent in case of separate usage of DNES or oxybutynin when compared with the one registered after the combined their usage(P <0.05).【Conclusion】Combined usage of DENS and oxybutinin(driptan) is effective in most severe cases in children suffered from neurogenic overactive bladder.