A Teelken

Cooling garment treatment in MS: Clinical improvement and decrease in leukocyte NO production

Ten heat-sensitive patients with MS were randomly allocated in a cross-over study to wear a cooling garment for 60 minutes at 7 °C (active cooling) and 26 °C (sham cooling). In contrast to sham cooling, active cooling improved fatigue and postural stability with eyes closed and muscle strength. There was no decrease in tympanic temperature, but active cooling was associated with a 41% decrease in mean leukocyte nitric oxide (NO) production (p = 0.004). This effect on NO could be relevant because it blocks conduction in demyelinated axons.

Insulin-like growth factor system in serum and cerebrospinal fluid in patients with multiple sclerosis

The insulin-like growth factor (IGF) system influences oligodendrocyte survival, myelination, and immune functions. We examined whether alterations in the circulating IGF system occur in multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system. We measured concentrations of IGF-I, IGF-II, and insulin-like growth factor binding proteins -1, -2, and -3 in both serum and cerebrospinal fluid from MS patients and age- and sex-matched controls. IGFBP-1 was not detectable in cerebrospinal fluid. We found no significant differences in any of the other components between patients with MS and controls.

Insulin-like growth factor II receptors in human brain and their absence in astrogliotic plaques in multiple sclerosis

Insulin-like growth factor (IGF) II receptors were studied in human adult brain by using autoradiography with [125I]IGF-II. Receptors were found to be widely distributed throughout all neuronal regions. The highest densities were found in plexus choroideus, granular layer of the cerebellar cortex, gyrus dendatus and pyramidal layer of the hippocampus, striatum, and cerebral cortex. White matter was devoid of IGF-II receptors. We also examined [125I]IGF-II binding in six plaques of multiple sclerosis, which were characterized by a dense network of astrocytes. We were unable to detect IGF-II receptors in any of the astrogliotic plaques, suggesting that IGF-II receptors in human brain are not involved in astrogliosis. The regional variations in neuronal distribution of IGF-II receptors suggest involvement of IGF-II in functions associated with specific neuronal pathways.

Low leucocyte myeloperoxidase activity in patients with multiple sclerosis

The gene for myeloperoxidase (MPO) has been implicated in multiple sclerosis (MS). By measuring H2O2 dependent oxidation of 3,3′5,5′-tetramethylbenzidine with spectrophotometry the authors investigated MPO activity in peripheral blood leucocytes from 42 patients with MS (12 with secondary progressive MS, 17 with primary progressive MS, and 13 with relapsing remitting benign MS) and 32 healthy controls. Leucocyte MPO activity was significantly lower in patients with benign MS (mean (SEM) 0.086 (0.029) U/mg protein; p<0.01), secondary progressive MS (0.038 (0.009) U/mg protein; p<0.001), and primary progressive MS (0.057 (0.016) U/mg protein; p<0.001) compared with healthy controls (0.322 (0.053) U/mg protein). These data suggest that low MPO, which may be genetically determined, plays a part in MS pathogenesis.

Peptidylarginine deiminase activity in postmortem white matter of patients with multiple sclerosis

The myelin sheath in multiple sclerosis (MS) appears to contain a higher proportion of the citrullinated isoform of myelin basic protein MBP-C8. In vitro, MBP-associated arginine is deiminated to citrulline by the enzyme peptidylarginine deiminase (PAD). We investigated PAD activity in white matter from postmortem human brain samples by measuring the formation of citrulline from benzoylarginine ethyl esther. PAD activity in MS white matter was not different from that in controls. In neonates, in whom MBP is exclusively of the C8 type, white matter PAD activity was not different from that in adults. Our results suggest that in human brain either PAD plays no role in the formation of MBP-C8, or there may be a better accessibility of MBP in myelin in neonates and MS to the enzyme.

On the nature of brain stem disorders in severe head injured patients

SummaryIn head injured patients changes were found in the CSF levels of metabolites of the dopaminergic and the serotonergic neurotransmission (HVA and 5-HIAA). After the fifth, day following trauma a significant derease of the HVA levels in the lumbar CSF after probenecid treatment was found. The intensity of this decrease was found to be related to the severity of the trauma (period of unconsciousness), but not to the state of consciousness.Also the probenecid-induced 5-HIAA levels in conscious patients were decreased after the fifth post-traumatic day. In unconscious patients, however, an increased turnover of serotonin was found to be also related to the period of unconsciousness, particularly in the period of 5–20 days after trauma. Between 21 and 60 days after trauma the 5-HIAA concentrations in unconscious patients decreased remarkably, but they were still significantly higher than in the conscious patients. It can be concluded that during unconsciousness serotonergic neurons have a high rate of turnover, but that both neurotransmitter systems are damaged by the direct or indirect consequences of the injury.

5-hydroxyindoleacetic acid (5-HIAA) levels in the cerebrospinal fluid in consciousness and unconsciousness after head injury

Abstract Concentrations of 5-hydroxyindoleacetic acid (5-HIAA) were determined in the lumbar cerebrospinal fluid (CSF) of patients after head injury. Unconscious patients showed after the fifth posttraumatic day no significant difference with the control group. The conscious patients showed significantly decreased 5-HIAA levels compared with the control group (following probenecid administration) as well as compared with the unconscious patients. These results suggest a relatively high cerebral serotonin turnover during the state of unconsciousness after head injury in man.