Tumor necrosis factor production in septic conditions following pancreatitis (preliminary report)]

Detectable TNF levels in sera 33% of patients with sepsis following pancreatitis have been found. No correlation was observed between serum TNF concentration and the severity of illness. However, monocytes and granulocytes of septic patients exerted higher TNF-mediated cytotoxicity than leukocytes of normal blood donors. The in vitro TNF-producing capacity was also higher in the patients in the study group, and it decreased only before fatal outcoming of sepsis. Our results suggest that determination of the TNF-producing capacity of leukocytes might be more informative than measurement of the serum TNF level in the evaluation of the severity or prognosis of sepsis.     

Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients

Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused by mutations of the argininosuccinate synthetase (ASS) gene, localized on chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle. Previously, we identified 32 mutations in the ASS gene of CTLN1 patients mainly in Japan and the United States, and to date 34 different mutations have been described in 50 families worldwide. In the present study, we report ASS mutations detected in 35 additional CTLN1 families from 11 countries. By analyzing the entire coding sequence and the intron-exon boundaries of the ASS gene using RT-PCR and/or genomic DNA-PCR, we have identified 16 novel mutations (two different 1-bp deletions, a 67-bp insertion, and 13 missense) and have detected 12 known mutations. Altogether, 50 different mutations (seven deletion, three splice site, one duplication, two nonsense, and 37 missense) in 85 CTLN1 families were identified. On the basis of primary sequence comparisons with the crystal structure of E. coli ASS protein, it may be concluded that any of the 37 missense mutations found at 30 different positions led to structural and functional impairments of the human ASS protein. It has been found that three mutations are particularly frequent: IVS6-2A>G in 23 families (Japan: 20 and Korea: three), G390R in 18 families (Turkey: six, U.S.: five, Spain: three, Israel: one, Austria: one, Canada: one, and Bolivia: one), and R304W in 10 families (Japan: nine and Turkey: one). Most mutations of the ASS gene are "private" and are distributed throughout the gene, except for exons 5 and 12-14. It seems that the clinical course of the patients with truncated mutations or the G390R mutation is early-onset/severe. The phenotype of the patients with certain missense mutations (G362V or W179R) is more late-onset/mild. Eight patients with R86H, A118T, R265H, or K310R mutations were adult/late-onset and four of them showed severe symptoms during pregnancy or postpartum. However, it is still difficult to prove the genotype-phenotype correlation, because many patients were compound heterozygotes (with two different mutations), lived in different environments at the time of diagnosis, and/or had several treatment regimes or various knowledge of the disease.     

Low levels of immunoglobulin A in children with intrinsic asthma: a possible protection against atopy

Immunoglobulin A and G (IgA, IgG) serum concentrations were detected in children with nonallergic/intrinsic (36 children) or allergic/extrinsic asthma (43 children) and in age-matching control children (40 children). Asthmatic children with allergic asthma had lower IgA (1.36+/-0.54 g/L) and higher IgG (10.48+/-2.77 g/L) levels than the age-matching control children group (1.63+/-0.69 vs. 9.01+/-2.32 g/L). Children with nonallergic/intrinsic asthma had lower IgA (1.03+/-0.41 g/L) ( p = 0.004) and IgG (8.38+/-1.93 g/L) (p = 0.001) levels than the allergic/extrinsic asthma group (1.36+/-0.54 vs. 10.48+/-2.77 g/L). Low IgA levels were found in children with nonallergic/intrinsic asthma and high IgG levels were found in those children with allergic/extrinsic childhood asthma. The hypothesis is that the increased incidence of asthma in the population may be caused by a decrease in childhood infections (hygiene hypothesis). Frequent infections in early life boost the immune system, stimulating Th1-type response in young children and reducing the risk of atopic diseases. Our hypothesis is that low IgA (and/or IgG) levels in our patients might be responsible for infection development among those children with nonallergic/intrinsic asthma. These infections stimulate the normal development of immune system in young children, reducing risk of atopy, so that those children do not get allergic/extrinsic childhood asthma. Intrinsic childhood asthma=nonallergic (nonatopic) childhood asthma. Extrinsic childhood asthma=allergic (atopic) childhood asthma.     

Adult-onset type II citrullinemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle

Citrin is a mitochondrial aspartate glutamate carrier primarily expressed in the liver, heart, and kidney. We found that adult-onset type II citrullinemia is caused by mutations in the SLC25A13 gene that encodes for citrin. In this report, we describe the frequency of SLC25A13 mutations, the roles of citrin as a member of the urea cycle and as a member of the malate-aspartate shuttle, the relationship between its functions and symptoms of citrin deficiency, and therapeutic issues.     

Meta-Analysis and Systematic Review of Micro- and Macro-Nutrient Intakes and Trajectories of Macro-Nutrient Supply in the Eastern Mediterranean Region

The Eastern Mediterranean Region (EMR) is experiencing a nutrition transition, characterized by the emergence of overnutrition and micro-nutrient deficiencies. No previous study has comparatively examined nutrient intake in adults across countries in the EMR. This review examined the adequacy of nutrients in adults living in the EMR. Moreover, it analyzed the food balance sheets (FBS) for 1961–2018 to identify the trajectory of energy supply from macro-nutrients in the EMR. A systematic search was conducted from January 2012 to September 2020. Only observational studies were retained with a random sampling design. An assessment of the methodological quality was conducted. Levels of nutrient daily intake and their adequacy compared to the daily reference intake of the Institute of Medicine were reported across the region. No studies were identified for half of the region’s countries. Although nutrient energy intake was satisfactory overall, fat and carbohydrate intake were high. Intake of vitamin D, calcium, potassium, zinc, and magnesium were below that recommended. The analysis of the FBS data allowed for the identification of four linear patterns of trajectories, with countries in the EMR best fitting the ‘high-energy-supply from carbohydrate’ group. This systematic review warrants multi-sectorial commitment to optimize nutrient intake.     

Vaccination with chimeric protein induces protection in murine model against ascariasis

An estimated 400 million people are infected by parasites of the genus Ascaris and the existing control measures are inefficient. Vaccine development using B cell antigens is a promising strategy for increased protection against this parasite. The present study aimed at developing a chimeric protein capable of conferring protection against infection by Ascaris sp. For this purpose, we performed B-cell epitope predictions on previously described vaccine candidate proteins from Ascaris suum and the corresponding peptides were used to construct a chimeric protein. Female BALB / c mice were immunized subcutaneously in three doses at 10 day intervals with a vaccine formulation comprised of the chimeric protein together with monophosphoryl lipid A (MPLA). Control groups included protein alone, MPLA, or PBS. After challenge infection, animals vaccinated with chimeric protein plus MPLA showed a reduction of 73.54% of larval load in the lung compared to control group animals. Animals immunized with chimeric protein plus MPLA also display higher IgG response and a reduction in lung inflammation. Our study highlights how chimeric proteins containing more than one B cell epitope can enhance immune protection against helminthic infection and offer new approaches to the development of Ascaris vaccines.     

2,3-Dichloro-5,6-dicyano-1,4-benzoquinone as a redox titrant

An oxidimetric titrant, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in anhydrous acetic acid is used for the semimicro-determination of hydrazine hydrate, phenylhydrazine hydrochloride, isoniazid and iproniazid phosphate in pure forms as well as in some pharmaceutical preparations containing isoniazid and iproniazid phosphate. The end point was detected potentiometrically using a platinum-calomel combination electrode. The results obtained are compared statistically with those obtained by the official methods and they are in good agreement.     

Osijek Health Center during the 1991-1992 war in Croatia

To assess the effectiveness of health services in the city of Osijek during the 1991-1992 war in Croatia, we followed the changes in the utilization of health services, morbidity and mortality, and completion of a vaccination plan during the 2 years of the war. We used a retrospective analysis of data from the Osijek Health Center and the Osijek County Institute of Public Health. The organization of health care during the war followed the concept of integrated health care and the instructions of the Ministry of Health. Visits to primary health care physicians decreased considerably, with a concomitant increase in disease and mortality. The plan for mandatory vaccination was not completed because of the evacuation of preschool and school children. The war changed the mode of health care use, the disease and mortality structure, and the implementation of mandatory vaccination. However, timely education and preparation of the health services to the war situation resulted in an adequate provision of health care to the population.