Social Cognition Impairments in Patients with Multiple Sclerosis: Comparison with Grade of Disability.

OBJECTIVES: Social cognitive impairments are an essential aspect of general disability in patients with multiple sclerosis (MS). They can manifest independently or in addition to physical deficits. AIM: To examine the impairment of social cognition and its potential relationship with the grade of disability in MS patients. SETTINGS AND DESIGN: Our study included 17 healthy controls and 36 patients with clinically definite MS (relapsing-remittent form) according to the McDonald Criteria (2010). The patients were divided into two groups - patients with Expanded Disability Status Scale (EDSS) <3.5 (N = 18) and those with EDSS ≥3.5 (N = 18). The neuropsychological battery included empathy assessment (Self-Compassion, "Reading the Mind") and theory of mind tests - ToM (Faux pas, cartoons). RESULTS: We did not register a change in self-assessment empathy in MS. Reading the Mind in Eye test showed a clear tendency for deterioration with increasing physical disability. The statistically significant difference (P < 0.05) between the results of controls and patients with EDSS ≥3.5 was registered. The tests for interpreting stories perceived in an auditory manner ("faux pas") showed a clear trend toward "failure" among patients (P < 0.05). The results of patients with high disability in ToM cartoons task were statistically worse (P < 0.01) both in comparison to those of controls and patients with EDSS <3.5. CONCLUSION: Our study found that, during the course of MS, deterioration of both social cognitive skills and basic cognitive abilities occurs, which is parallel to physical disability.

Assessment of frequency-dependent alterations in the level of extracellular Ca2+ in the synaptic cleft.

The synaptic cleft may be represented as a very thin disk of extracellular fluid. It is possible that at high stimulation frequencies the interval between pulses would be insufficient for diffusion of Ca2+ from the periphery of the cleft to replace extracellular Ca2+ depleted at the center of the cleft as a result of activation of postsynaptic, Ca2(+)-permeable channels. Computer modeling was employed to assess the impact of activation of glutamate receptor channels (GRCs) in the postsynaptic membrane on the level of extracellular Ca2+ within the synaptic cleft. The model includes calcium influx from the synaptic cleft into the postsynaptic compartment through GRC and calcium efflux through calcium pumps and Na/Ca exchangers. Concentrations of extracellular Ca2+ inside the cleft are estimated by using a compartmental model incorporating flux across the postsynaptic membrane and radial diffusion from the edges of the cleft. The simulations suggest that substantial extracellular Ca2+ depletion can occur in the clefts during activation of GRCs, particularly at high stimulation frequencies used to induce long-term potentiation (LTP). Only minimal transitory changes in extracellular Ca2+ are observed at low frequencies. These frequency-dependent alterations in extracellular Ca2+ dynamics are a direct reflection of the activity of GRCs and could be involved in the modulation of presynaptic function via a retrograde messenger mechanism, if there are extracellular Ca2+ sensors on the presynaptic membranes. The recently cloned extracellular Ca2(+)-sensing receptors that are known to be present in nerve terminals in hippocampus and other areas of the brain could potentially play such a role.

Effects of low molecular weight glycoproteins in chronic hepatitis B.

BACKGROUND/AIMS: We evaluated the effect of low molecular weight glycoproteins isolated from animal spleen (Polyerga) in ten patients with biopsy proven chronic HBV infection with ongoing replication. MATERIAL AND METHODS: Polyerga was given intramuscularly trice weekly and orally 3 tablets daily for 24 weeks. The effect on viral replication was evaluated by measuring HBV-DNA and HBeAg in serum. RESULTS: In three out of ten, HDV-DNA became undetectable and ALT decreased (mean pre-treatment ALT 87.2 +/- 55.38SD, mean post-treatment ALT 62.6 +/- 41.86SD p = 0.026 t-test and Wilcoxon test p = 0.014). During the first month of Polyerga application transient increase of serum ALT was observed in 50%. In HBeAg negative patients and in patients with low pre-treatment level of HBV-DNA (below 250pg/ml) there was significant decrease of ALT by t-test (p = 0.022), Wilcoxon (p = 0.028) and Sign test (p = 0.041) in contrast to those with HBV-DNA above 250pg/ml. CONCLUSION: The effect of increasing the cytolysis shows that these drugs are active, probably by increasing the lymphokine secretion and the generation of cytotoxic T-cells. The absence of side effects, its ability to reduce viral replication and lower ALT activity even in patients with liver cirrhosis warrants further studies as a "second drug" or as a drug of choice when IFN is contraindicated.

GI amyloidosis treated with megadoses of i.v. gammaglobulin.

A 50-year-old-man with peripheral edema and muscle cramps without proteinuria as presenting symptoms was found to have hypoproteinemia due to amyloidosis of the stomach. After failure to control the symptoms with diuretics, oral calcium supplement and colchicine, large doses of intact gamma-globulin (250 mg/kg bodyweight, total, 3 separate infusions every other day) infused i.v., helped to control the symptoms for more than 8 months.

Heterogeneity of hepatitis B virus C-gene sequences: implications for amplification and sequencing.

Occasionally direct sequencing of amplified hepatitis B virus DNA leads to weak signals on autoradiograms. Using amplified C-gene sequences we investigated whether this is due to sequence heterogeneity of virus populations and use of inappropriate primers for direct sequencing. High C-gene sequence heterogeneity (point mutations, stop codons and a one codon deletion) was observed in HBV genomes from serum of a chronic carrier who underwent interferon treatment. The type of C-gene mutations detected by direct sequencing depended on the type of primers used. Cloning and sequencing of amplified C-gene sequences demonstrated that this was due to mutations in the region complementary to the sequencing primer. These data demonstrate the existence of novel HBV C-gene mutants and imply that multiple or degenerate sequencing and amplification primers are essential for accurate evaluation of the extent of HBV C-gene heterogeneity. Based on comparative sequence analysis of all available completely or incompletely sequenced C-genes, guidelines for optimal primer design are proposed for similar studies.