Serum and CSF immunological findings were analysed in 37 patients with amyotrophic lateral sclerosis (ALS). ALS patients had significantly higher mean values of serum IgG and complement component C4 and significantly lower mean value of total haemolytic titre of complement (THC) compared with normal controls. Incidence of immune complexes (ICs) was significantly higher in sera of ALS patients than in normal controls. There was no significant difference regarding mean serum levels of IgM, IgA, and complement components C3 and Factor B between patients and controls. The blood-brain barrier (BBB) damage was found in 46% of patients. Intrathecal IgG synthesis was detected in six patients (16%). These results support the hypothesis of immune system involvement in ALS.
The ratios of E/Z isomers of sixteen synthesized 1,3-dihydro-3-(substituted phenylimino)-2H-indol-2-one were studied using experimental and theoretical methodology. Linear solvation energy relationships (LSER) rationalized solvent influence of the solvent-solute interactions on the UV-Vis absorption maxima shifts (ν) of both geometrical isomers using the Kamlet-Taft equation. Linear free energy relationships (LFER) in the form of single substituent parameter equation (SSP) was used to analyze substituent effect on pK, NMR chemical shifts and ν values. Electron charge density was obtained by the use of Quantum Theory of Atoms in Molecules, i.e. Bader's analysis. The substituent and solvent effect on intramolecular charge transfer (ICT) were interpreted with the aid of time-dependent density functional (TD-DFT) method. Additionally, the results of TD-DFT calculations quantified the efficiency of ICT from the calculated charge-transfer distance (D) and amount of transferred charge (Q). The antimicrobial activity was evaluated using broth microdilution method. 3D QSAR modeling was used to demonstrate the influence of substituents effect as well as molecule geometry on antimicrobial activity.
The energy imbalance related predisposition to mastitis was studied in group-fed postpartum dairy cows (n = 333) kept in 4 large-scale units and producing milk of low somatic cell count (SCC). Blood samples were taken on Days 1-3 after calving for assaying some metabolites and hormones related to the negative energy balance (NEB). If mastitis was diagnosed later, aseptic milk samples were taken to identify the pathogens. Considering pathogen types [contagious pathogens: Staphylococcus (S.) aureus, Gram-positive (GP) environmental pathogens, and Gram-negative (GN) environmental pathogens + mastitis with no detectable pathogens (NDP)] separately, stepwise logistic regression was used to analyse the relation between the potential prognostic value of hormones and metabolites and mastitis outbreak. Only the elevated (≥ 1.00 mmol/l) serum β-hydroxybutyrate (BHB) levels predisposed the cows to mastitis in the subsequent 4 weeks. This prognostic value of BHB was significant only in GN + NDP mastitis and in cases caused by GP environmental pathogens, but not in S. aureus mastitis (odds ratio: 5.333, 3.600 and 1.333, respectively).
Transition from pregnancy to lactation in dairy cows involves considerable metabolic adaptation. Additional stress is incurred during infections such as periparturient mastitis. Multiparous Holstein-Friesian cows kept under normal production conditions (n = 15) were used to evaluate changes in circulating metabolite and hormone concentrations from 5 days before to 5 days after calving. Insulin-like growth factor binding protein (IGFBP) profiles were also monitored. Marked time-related changes were observed for plasma thyroid hormone, IGF, cortisol, insulin, beta-hydroxybutyrate (BHB) and non-esterified fatty acid (NEFA) concentrations but not for plasma leptin. A decrease in IGF-II concentration and maximal intensity of the putative IGFBP-1 band occurred at parturition. When compared with the five healthy cows,low IGF-II levels were prolonged to day 2 post-partum in five cows with Escherichia coli-associated mastitis. However, marked decreases in IGFBP-2 band intensity were evident only in two of the four cases examined. Individual total ligand (IGF-I + IGF-II) concentration and IGFBP pattern prepartum were largely regained 5 days post-partum in all cows. Hormone and metabolite concentrations in the two cows with Staphylococcus aureus-associated mastitis were very similar to those in the five healthy cows. Plasma thyroxine (T4) was lower 2 days prepartum in the cows, which later developed Gram-negative mastitis. Multiregression analysis showed that variance in T4 concentration was significantly and independently associated with triiodothyronine (T3) and IGF-I positively and with cortisol negatively (R2 = 0.648). This study confirms the close inter-relationship between the thyroid hormone and IGF axes in cattle and indicates possible effects of Gram-negative mastitis infection on IGF-II metabolism.
Ten patients in acute exacerbation of multiple sclerosis were treated with 1000 mg of methylprednisolone for 7 days, followed by abrupt cessation of therapy. The function of hypothalamic-pituitary-adrenal (HPA) axis was assessed by the response of ACTH and cortisol to insulin tolerance test (ITT). ITT was performed 1 day before and 1, 3, 8, 13 and 23 days after the termination of the therapy (days 0, 8, 10, 15, 20 and 30 of the study, respectively). The response of these hormones to insulin-induced hypoglycemia prior to therapy was normal. There was no suppression of the ACTH response to hypoglycemia after the methylprednisolone therapy based on the 100% rise of ACTH after ITT. Cortisol response during ITT was suppressed at day 8 (1 day after ending of therapy) but recovered on day 10 (3 days after ending of therapy). In conclusion, 7 day-therapy with 1000 mg methylprednisolone does not result in the permanent suppression of the HPA axis, suggesting that no regular supplemental corticosteroid coverage is required. The observed transitory suppression of the HPA axis recovered spontaneously after the therapy.
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