Transplantation of microencapsulated bovine chromaffin cells reduces lesion-induced rotational asymmetry in rats

Surrounding bovine chromaffin cells by a semipermeable membrane may protect the transplanted cells from a host immune response and shield them from the inflammatory process resulting from the surgical trauma. Encapsulation of the chromaffin cells was achieved by inter-facial adsorption of a polycation on a polyanionic colloid matrix in which the chromaffin cells were entrapped. Basal and potassium-evoked release of catecholamines from encapsulated bovine chromaffin cells was analyzed over a 4-week period in vitro. Norepinephrine and dopamine release remained constant over time whereas epinephrine release significantly decreased. The chromaffin cells also retained the capacity for depolarization-elicited catecholamine release 4 weeks following the encapsulation procedure. Morphological analysis revealed the presence of intact chromaffin cells with well-preserved secretory granules. Striatial implantation of chromaffin cell-loaded capsules significantly reduced apomorphine-induced rotation compared to empty polymer capsules in animals lesioned with 6-hydroxydopamne frr at least 4 weeks. Intact chromaffin cells expressing tyrosine hydroxylase and dopamine-β-hydroxylase were observed in all capsules implanted in the striatum for 4 weeks. The assessment of the clinical potential of transplanting encapsulated adrenal chromaffin cells of either allo- or xenogeneic origin for Parkinson's disease will require long-term behavioral studies. The present study suggests, however, that the polymer encapsulation procedure may offer an alternative to adrenal autografts as a source of dopaminergic tissue.     

Toward a more viable model of grieving and consequences for older persons

Most theories of grieving derive from Sigmund Freud and Erich Lindemann's understanding of mourning and include two assumptions: (a) Grieving is time limited; the process should be completed or resolved after a year or two; and (b) The main task of grieving is to achieve “decathexis.” One should detach oneself from emotional ties to the deceased so as to be able to form new relationships. This study presents evidence that these assumptions are flawed and that modern theories of grieving fall short of explaining the complicated reality of the mourning process. An alternative model is presented arguing that when a “high-grief” death occurs, a griever may be able to adapt and adjust to loss, but the grieving continues indefinitely. Implications of this model for older grievers are explored.     

Steroids in Duchenne muscular dystrophy--deflazacort trial

We conducted a double blind controlled trial in 28 Duchenne muscular dystrophy (DMD) patients with Deflazacort (DF), an oxazoline derivative of prednisolone which reduces its side-effects. Myometric muscle strength measurements, Scott Score and timed tests showed statistically significant improvement for the treated group (P less than 0.05). Side-effects after 9 months of treatment included mild cushingoid appearance in four patients (28%) and moderate in only one (7%), increased appetite in seven (50%), increased body hair in four (28%), irritability and hyperactivity in three (21%). Increased body weight was not prominent and was controlled with dietary measures. No patient had to be withdrawn from medication. More research and long-term follow-up are needed in order to establish the mechanism of improvement and the consequences of long-term steroid administration in DMD. In this regard DF appears as an alternative to prednisone preserving its benefits but with fewer side-effects.     

Possible mechanisms of morphine analgesia.

The body has an endogenous analgesic system that prevents excess pain from interfering with the normal body functions. Depression of pain sensations occurs within the dorsal horn of the spinal cord where the primary pain fibers, which transmit pain sensations from the periphery, synapse with neurons that transmit pain to the higher centers. There appear to be two mechanisms by which the transmission of pain sensations are depressed; these include hyperpolarization of interneurons within the dorsal cord and depressing the release of the neurotransmitters associated with pain transmission. Activation of the analgesic mechanisms results from an interaction between specific neurotransmitters, such as enkephalin, serotonin, or norepinephrine, and specific receptors located on the neurons that transmit pain. The spinal analgesic mechanisms can be activated by either pain or nonpainful sensations arriving from the periphery or by supraspinal mechanisms. The supraspinal mechanisms originate in specific structures within the brainstem that include the periaqueductal gray matter, locus ceruleus, and nuclei in the medulla. These systems are activated either by ascending pain impulses or by higher centers such as the cortex or hypothalamus that, in turn, activate the spinal analgesic systems. There are three systems associated with activation of the supraspinal mechanisms. These include the opioid system associated with the release of the endorphins, the adrenergic system associated with the release of norepinephrine, and the serotonergic system associated with the release of serotonin. The interaction between these systems activates the spinal analgesic system. When the endogenous analgesic systems fail to control pain, analgesic drugs can be used to enhance the endogenous systems. Opiate drugs, such as morphine, interact with opioid receptors and produce analgesia by the same mechanisms as enkephalin, i.e., hyperpolarization of interneurons and depressing the release of transmitters associated with transmission of pain. In addition, morphine can interact with opioid receptors located in the supraspinal structures and activate the supraspinal system. Adrenergic drugs that interact with specific receptors also produce analgesia and it has been suggested that morphine interacts with the adrenergic system to produce analgesia.     

Basicranial diastematomyelia: a case report

Diastematomyelia is a congenital dysraphism of the spinal cord in which the affected segment is longitudinally divided by a band of fibrous tissue, cartilage, or bone. Diastematomyelia has been well described in the cervical, thoracic, lumbar, and sacral spinal cord; this paper presents a case involving the basicranium. Based on the early embryologic development of the basicranium and brain, this case demonstrates that the same mechanisms proposed as the origin of spinal diastematomyelia may also operate at a more cephalad level.     

Auriculo-ventricular block and distal myopathy with rimmed vacuoles and desmin storage.

A young patient had an auriculo-ventricular block and a distal myopathy with muscle biopsy findings suggestive of inclusion body myositis. What was most unusual was the presence of numerous sarcoplasmic bodies identified as desmin by electron microscopy and immunocytochemistry. The nosological situation of this condition is discussed.     

Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy.

We examined binding to excitatory amino acid and inhibitory amino acid receptors in frozen hippocampal sections prepared from surgical specimens resected from 8 individuals with medically refractory temporal lobe epilepsy. The excitatory receptors studied included N-methyl-D-aspartate (NMDA), strychnine-insensitive glycine, phencyclidine, and quisqualate. The inhibitory receptors studied were gamma-aminobutyric acid type A (GABAA) and benzodiazepine. Excitatory and inhibitory amino acid receptor binding were differentially altered in the patients with temporal lobe epilepsy in comparison to 8 age-comparable autopsy control subjects, and changes in receptor binding were regionally selective in four areas. Binding to phencyclidine receptors associated with the NMDA channel was reduced by 35 to 70% in all regions in the hippocampi of the patients. In contrast, binding to the NMDA recognition site and its associated glycine modulatory site was elevated by 20 to 110% in the cornu ammonis (CA) 1 area and dentate gyrus of the hippocampus of the patients. Binding to these sites was unaffected in area CA4. Binding to the quisqualate-type excitatory amino acid receptor was unchanged in all regions except the stratum lacunosum moleculare CA1, where it was increased by 63%. GABAA and benzodiazepine receptor binding was reduced by 20 to 60% in CA1 and CA4, but unchanged in dentate gyrus. The data indicate that excitatory and inhibitory amino acid receptors are altered in the hippocampus of patients with temporal lobe epilepsy.     

Increased lymphocyte beta-adrenergic receptor density in progressive multiple sclerosis is specific for the CD8+, CD28- suppressor cell.

Beta-adrenergic receptor density on T cells from healthy humans is greatest on suppressor cells (CD8+, CD28-) and the effect of catecholamines, secreted by the sympathetic nervous system, predominates on this subset. The sympathetic skin response, a measure of sympathetic nervous system function, is absent in most patients with chronic progressive multiple sclerosis (MS). We measured beta-adrenergic receptor density on suppressor cells, cytotoxic cells, and monocytes from patients with chronic progressive MS and healthy control subjects. Control receptor density on suppressor cells was 2.8 +/- 0.3 fmol/10(6) cells versus a density of 5.1 +/- 0.7 fmol/10(6) cells for patients. Cytotoxic cell (CD8+, CD28+) receptor density was 1.4 +/- 0.4 fmol/10(6) cells in control subjects and 0.9 +/- 0.3 fmol/10(6) cells in the patients. Monocytes displayed beta-adrenergic receptor densities of 2.6 +/- 0.4 fmol/10(6) cells in normal individuals and 2.7 +/- 0.4 fmol/10(6) cells in the patient group. CD8 lymphocyte beta-adrenergic receptor densities in patients with relapsing-remitting and those with stable MS were not different from control values, yet were significantly less than the values for patients with chronic progressive MS. We find that mononuclear cells from healthy control subjects and patients with chronic progressive MS proliferate in response to 200 units/ml of recombinant human interleukin-2 (IL-2) similarly. However, IL-2 treatment increased beta-adrenergic receptor density on normal mononuclear cells, but failed to increase it on mononuclear cells from patients with chronic progressive MS.(ABSTRACT TRUNCATED AT 250 WORDS)