Breast cancer (BC) is quite often accompanied by affection of the bones and alterations in mineral metabolism. The most important clinical manifestations of the above processes that appeared to a considerable extent to be a cause of a poor condition of patients include pains in bones, pathological fracture and hypercalcemia. Metastatic events in the skeleton bone are recordable in 13.5 to 85 percent of cases, as evidenced by autopsy findings. In BC patients presenting with hormone-dependent tumours and metastases in the bones, indices for survival tend to be much higher than in those patients with solid tumours of other localization. The higher level of survival in such patients warrants an effective palliative treatment to be instituted to improve quality of their lives.
The changes in neuronal Ca2+ homeostasis were studied on dorsal horn neurons from spinal cord rat slices and freshly isolated dorsal root ganglion neurons of mice in control condition and under streptozotocin (STZ)-induced diabetes. The cytoplasmic free Ca2+ concentration ([Ca2+]i) was measured using fura-2 and indo-1 based microfluorimetry. The recovery of depolarization-induced [Ca2+]i increase was delayed in diabetic neurons compared with normal animals. The amplitude of calcium release from caffeine-sensitive endoplasmic reticulum calcium stores became significantly smaller in diabetic neurons. The participation of mitochondria in [Ca2+]i homeostasis was determined by investigation of changes which occurred after addition of mitochondrial protonophore (CCCP) to the extracellular solution. In control cells 10 (M CCCP applied before membrane depolarization induced an increase of the amplitude of depolarization-induced [Ca2+]i transients and disappearance of their delayed recovery, indicating the participation of mitochondria in fast uptake of Ca2+ ions from the cytosol during the peak of the transient and subsequent slow release them back during its decay. In neurons from diabetic animals the increase of the peak transient amplitude under the action of CCCP became diminished, and the delayed elevation of [Ca2+]i disappeared in small size neurons. We conclude that streptozotocin-induced diabetes is associated with prominent changes in the mechanisms responsible for [Ca2+]i regulation in neurones of the nociceptive system, which presumably include a slow down of Ca2+ elimination from the cytoplasm by endoplasmic reticulum and mitochondria.
Substances modulating calcium permeability of cell membrane (verapamil imidazol, 4-aminopyridine), decreasing motor activity (meprobamate) and blocking adrenoreceptors (clophelin, propranolol, droperidol, aminazine++ have been studied for their action on the monosynaptic discharge of the ventral roots (MD VR) reinforced due to chronic cutting of the spinal cord. It is found that verapamil and meprobamate depress more strongly MD VR of rats with chronic cutting of the spinal cord than of those with the acute one. Imidazol and 4-aminopyridine reinforcing MD VR of rats with acute cutting of the spinal cord have no influence on the analogous index of rats with chronic cutting of the spinal cord. Adrenoblockers do not change the amplitude of MD VR in both groups of the animals.
Immunohistochemical studies of c-fos expression in the lumbar and neck segments of spinal cord after fatiguing stimulation of the mm. gastrocnemius-soleus or m. trapezius and m. splenius, were carried out on the anaesthetized (chloral-hydrate 400 mg/kg, i.p.) rats. The patterns of the Fos-immunoreactive neurons distribution in the grey matter of spinal cord in the L4 and L5 segments, as well as the C2 and C3 were similar. The highest number of marked cells was registered in the dorsal horn in the first, fourth and fifth layers of grey matter, i.e. within the areas of termination of high-threshold muscle afferents of group III and IV. It is assumed, that the types of afferents could be activated by muscle fatigue-induced metabolites. The signals incoming to the spinal cord could be involved into the presynaptic inhibition of muscle spindle volleys than resulted in the impairment of motor output performance. This mechanism is substantial for limitation of the force of muscles contraction and prevention the injury of the muscles under the excessive physical loading.
Two different types of myelopathy course were discerned: myelopathy due to instability, occurring early after trauma, rapidly progressing and myelopathy due to the long lasting ventral compression of spinal cord at the craniocervical level, occurring in several years after trauma, slowly progressing. The conduction of occipitocervical spondilodesis using metal loop with the vertebral arches fixation in myelopathy due to instability and odontoidectomy in the spinal cord ventral compression on craniocervical level constitutes the method of choice for the late complications in craniocervical junction trauma.
We studied the immunocorrective effect of the allogenic new-born brain cells on the model of rats experimental allergic encephalomyelitis (EAE). EAE was induced by the immunization of old rats spinal cord homogenate in Freund's adjuvant. Correction was carried on the 12-th, 14-th, 16-th day after the induction of the EAE by the intraperitoneum injection of rat's new-born brain fractions enriched with neurons and glial cells. A positive clinical effect was achieved by the employment of neurons (the stabilization of encephalomyelitis and the acceleration of the recovery). The glia correction was accompanied by the aggravation in the course of encephalomielitis and by extension of its clinical manifestation period. The obtained results testify to the existence of both an immunoregulative and a neurotrophic influence of the neuron fraction of the new-born brain cells. The mechanism of a corrective effect needs further special investigation.