Nutrition management guideline for very-long chain acyl-CoA dehydrogenase deficiency (VLCAD): An evidence- and consensus-based approach.

The nutrition management guideline for very-long chain acyl-CoA dehydrogenase deficiency (VLCAD) is the fourth in a series of web-based guidelines focusing on the diet treatment for inherited metabolic disorders and follows previous publication of guidelines for maple syrup urine disease (2014), phenylketonuria (2016) and propionic acidemia (2019). The purpose of this guideline is to establish harmonization in the treatment and monitoring of individuals with VLCAD of all ages in order to improve clinical outcomes. Six research questions were identified to support guideline development on: nutrition recommendations for the healthy individual, illness management, supplementation, monitoring, physical activity and management during pregnancy. This report describes the methodology used in its development including review, critical appraisal and abstraction of peer-reviewed studies and unpublished practice literature; expert input through two Delphi surveys and a nominal group process; and external review from metabolic physicians and dietitians. It includes the summary statements of the nutrition management recommendations for each research question, followed by a standardized rating based on the strength of the evidence. Online, open access of the full published guideline allows utilization by health care providers, researchers and collaborators who advise, advocate and care for individuals with VLCAD and their families and can be accessed from the Genetic Metabolic Dietitians International (https://GMDI.org) and Southeast Regional Genetics Network (https://southeastgenetics.org/ngp) websites.

Effect of melatonin supplementation on plasma lipid hydroperoxides, homocysteine concentration and chronic fatigue syndrome in multiple sclerosis patients treated with interferons-beta and mitoxantrone.

UNLABELLED: Multiple sclerosis (MS) prevalence is higher in geographic regions with less sunlight exposure. Melatonin participates in the effects of sunlight in healthy individuals and could play a role in MS pathophysiology. Melatonin crosses the blood-brain barrier and exerts antioxidative, immunomodulatory, and anti-inflammatory effects. Chronic fatigue syndrome concerns 80 - 90% MS patients. The pathophysiology of chronic fatigue syndrome is unknown, however activation of immune, inflammatory, oxidative and nitrosative stress mechanisms and plasma lipid peroxide elevation was reported. Homocysteine increases plasma lipid hydroperoxides levels. The aim was to determine the effect of melatonin supplementation on chronic fatigue syndrome in MS patients and evaluate plasma lipid hydroxyperoxides (LHP) and homocysteine concentrations as a potential biochemical fatigue biomarkers. Into a case-control prospective study 102 MS patients divided according receiving immunomodifying MS treatment into groups: RRMS-pretreated, RRMS-INF-beta, SP/PPMS-mitoxantrone, RRMS-relapse were enrolled. Patients were supplemented with melatonin over 90 days. Plasma LHP, homocysteine concentration, brain MRI and fatigue score were examined. Results show that LHP concentrations were significantly higher in all studied MS groups vs. CONTROLS: In all MS patient groups melatonin application resulted in significant decrease in plasma LHP concentrations. Plasma homocysteine concentration was similar in healthy people, RRMS-pretreated, RRMS-INF-beta and SP/PP-MS-mitoxantrone groups. However, in the RRMS-relapse group plasma levels of homocysteine were significantly higher compared to the RRMS-pretreated group. There were no significant differences in plasma homocysteine concentration in the studied groups before and after melatonin application. The fatigue score was significantly lower in RRMS pretreated group compared to RRMS-INF-beta and SP/PP MS-mitoxantrone treated patients. Plasma lipid hydroxyperoxides could be potential biochemical chronic fatigue syndrome biomarker in MS patients and homocysteine could be a potential marker of acute phase of MS. Melatonin exerts beneficial effects in MS patients based on its' proved antioxidative properties.

Calcium-phosphate metabolism in patients with multiple sclerosis.

INTRODUCTION AND OBJECTIVES: The purpose of this study was to evaluate the concentration of 25-hydroxycholecalciferol and parameters of calcium-phosphate metabolism at different periods of relapsing-remitting multiple sclerosis (RRMS). MATERIALS AND METHODS: Forty-five patients, residents of Poland (49°-50°, N), were enrolled in the study, i.e. 15 immediately after the diagnosis of RRMS, 15 at the early stage and 15 at the advanced stage of RRMS. The results were compared to values obtained in 20 age- and sex-matched controls. RESULTS: Lower serum concentrations of 25-hydroxycholecalciferol and ionised calcium were found in patients compared to the control group. In patients with the disease duration of 5-6 years, concentrations of 25-hydroxycholecalciferol and ionised calcium were lower than in patients in the earlier period of RRMS. The inverse and clearer direction of changes was found in parathormone serum concentration in patients compared to the controls. In patients with a longer disease duration, a significantly lower 25-hydroxycholecalciferol concentration was found in female patients compared to male patients. In patients, more frequent 25-hydroxycholecalciferol and unsaturated fatty acids' supplementation was observed compared to the controls. CONCLUSIONS: In RRMS patients, calcium-phosphate metabolism is disturbed which increases during disease progression.

Influence of melatonin supplementation on serum antioxidative properties and impact of the quality of life in multiple sclerosis patients.

The relationship between the prevalence of multiple sclerosis (MS) and sunlight's ultraviolet radiation was proved. Oxidative stress plays a role in the pathogenic traits of MS. Melatonin possesses antioxidative properties and regulates circadian rhythms. Several studies have reported that the quality of life is worse in patients with MS than in healthy controls, with a higher prevalence of sleep disturbances, depression and fatigue. The aim of study was to evaluate 5 mg daily melatonin supplementation over 90 days on serum malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity and its' influence on impact of the quality of life of MS patients. A case-control prospective study was performed on 102 MS patients and 20 controls matched for age and sex. The EDSS, MRI examinations and Multiple Sclerosis Impact Scale (MSIS-29) questionnaire was completed. Marked increase in serum MDA concentration in all MS patients groups was observed and after melatonin treatment decreased significantly in interferons-beta and glatiramer acetate-treated groups, but not in mitoxantrone-treated group. A significant increase in SOD activity compared to controls only in glatiramer acetate-treated group was observed. After 3 months melatonin supplementation the SOD activity increased compared to initial values in interferons beta-treated groups. A significant increase in both MSIS-29-PHYS and MSIS-29-PSYCH items mean scores only in the MX group as compared to other groups was observed. There were no significant differences in mean MSIS-29-PHYS was observed before and after melatonin therapy. Melatonin supplementation caused a decrease in mean MSIS-29-PSYCH scores compared to initial values in interferons beta-treated groups. Finding from our study suggest that melatonin can act as an antioxidant and improves reduced quality in MS patients.

Intrahepatic interleukin-2 with chemotherapy for unresectable liver metastases: a randomized multicenter trial.

BACKGROUND/AIMS: A pilot study of Interleukin-2 (IL-2) with chemotherapy for unresectable colorectal liver metastases revealed a favorable response rate (76%). This prospective, randomized, multicenter study was conducted to evaluate the efficacy of this treatment protocol. METHODOLOGY: Over a period of 32 months, 46 patients with unresectable liver metastases were randomly assigned to 1 of 3 treatment groups: group A: chemotherapy alone, group B: chemotherapy plus high-dose, intermittent IL-2 (2.1 x 10(6) U twice weekly) or group C: chemotherapy plus low-dose, continuous IL-2 (7 x 10(5) U daily). Treatment continued for 4 weeks in the hospital and on an outpatient basis according to the clinical response. No crossover between treatment arms was permitted. RESULTS: IL-2 combined with chemotherapy produced a higher complete and partial response rate of 40% in group A, 60% in group B, and 78% in group C. Toxicity related to IL-2 included fever, chills, malaise, and eosinophilia. CONCLUSIONS: Hepatic arterial infusion of chemotherapy plus IL-2 resulted in an increased tumor response when compared with chemotherapy alone. To confirm the efficacy of this treatment protocol, we have started a large-scale, randomized, multi-institution trial.

[The effect of hyperthermia against pancreatic cancer cell--various examinations including flow cytometric bromodeoxyuridine/DNA analysis].

We investigated the effect of hyperthermia against pancreatic cancer cell in various aspects including of cytokinetics. The hyperthermia above 43 degrees C was thought to have strong effect for the studies on surviving cell number and morphological change of Capan-2 and RWP-1 cells after heating treatment. The cell inoculated to the nude mice subcutaneously after heating treatment at 43 degrees C was recognized the tumor forming at 3 weeks later, however, the growth speed was slower than that of control to which untreated Capan-2 cells were inoculated. As the case of 44 degrees C, the tumor forming was not recognized at all. The cytokinetics was measured by flow cytometric bromodeoxyuridine (BrdUrd)/DNA analysis. Up to 43 degrees C in accordance with increase in the heating temperature, the accumulation in G2M phase increased, and the amount of BrdUrd incorporated 5 phase decreased. At the temperature above 44 degrees C, BrdUrd was hardly incorporated into S phase cells and the cell cycle was almost stopped. These results suggested the usefulness of hyperthermia and strong effect of heating treatment above 44 degrees C against pancreatic cancer cell.

Flow cytometric bromodeoxyuridine/DNA analysis of hyperthermia and/or adriamycin for human pancreatic adenocarcinoma cell line Capan-2.

The effects of hyperthermia, adriamycin (ADM), and hyperthermia combined with ADM on pancreatic cancer cells were investigated from the viewpoint of cytokinetics using flow cytometric bromodeoxyuridine (BrdUrd)/DNA analysis. Human pancreatic adenocarcinoma cell line Capan-2 was used. The untreated cells could be clearly divided into G1, S, G2M phases on contour plots of BrdUrd/DNA distribution. After heat treatment at 41-43 degrees C, there was an accumulation of cells in the G2M phase which was correlated with the increase in temperature. After heat treatment at 44 or 45 degrees C, there was marked increase in non BrdUrd-labeled cells in the S phase. ADM caused no change in the percent of non BrdUrd-labeled cells in the S phase, even after treatment with a concentration of 1.0 micrograms/ml, though that concentration of ADM caused a marked increase in the percent of cells in the G2M phase. After hyperthermia combined with ADM, the accumulation of the G2M phase increased remarkably, and was significantly higher than that after each treatment alone (P less than 0.005); however, non BrdUrd-labeled cells in the S phase did not increase. In this study the synergistic effect of hyperthermia combined with ADM in increasing the percent of cells in the G2M phase could be observed by flow cytometry. The study illustrates the importance of performing in vitro flow cytometric BrdUrd/DNA analysis of combined therapy prior to the use of the combined therapy in patients.

Evaluation of ceftazidime, ampicillin and chloramphenicol in experimental Haemophilus influenzae type b meningitis.

In an infant rat model of Haemophilus influenzae, type b meningitis, where treatment was given 24 and 48 h after infection, the dose of ceftazidime required to eradicate the infection from the CSF of half the animals (CD50) ranged from less than 0.15-1.5 mg/kg/dose. The accompanying blood infections were marginally less responsive to therapy with CD50 values ranging from 0.5-3.9 mg/kg/dose. Comparable data for ampicillin were 12.5-40 mg/kg/dose and 20- greater than 200 mg/kg/dose for the CSF and blood infections while those for chloramphenicol were 18- greater than 100 mg/kg/dose and 22- greater than 100 mg/kg/dose for the CSF and blood infections respectively. Investigation of the relative rates of kill in vivo showed that all three drugs rapidly reduced the bacterial numbers to minimal levels. However, whereas ceftazidime completely eradicated the infection, chloramphenicol, and to a lesser extent, ampicillin-treated rats experienced substantial relapsing. Ceftazidime penetrated into the CSF of infected and uninfected rats slightly better than ampicillin--7.3% compared to 4.0% of the corresponding blood levels respectively. These results indicate that ceftazidime is significantly more active in the infant rat model of H. influenzae, type b meningitis than ampicillin or chloramphenicol.

Pancreatography with contrast medium containing polyethylene hydrogenated castor oil.

A new contrast medium has been used for endoscopic pancreatography. Good visualization of the pancreas was obtained by this method. No side-effects of this method were observed by clinical and histologic examination, either in clinical or experimental studies. Clinically, the new method provided more detailed information regarding pancreatic changes in chronic pancreatitis. It is suggested that this method may make detection of a small tumor of the pancreas in the parenchyma and permit earlier diagnosis of carcinoma of the pancreas.