Free Fatty Acids of Newborns from Women with Gestational Diabetes Mellitus.

INTRODUCTION: Fetal macrosomia in gestational diabetes mellitus is contributed to by compensatory fetal mechanisms responding to alterations in maternal metabolism. OBJECTIVES: To compare FFA and blood glucose concentrations of newborns derived from healthy and hyperglycemic mothers. METHODS: Prospective study included two equal groups of term newborns (50) from GDM and healthy mothers. Blood was derived from umbilical and cubital vein of mothers immediately after birth. RESULTS: The mean FFA concentration of mothers did not differ whereas in infants of GDM mothers FFA were significantly lower. A significant correlation was found between FFA levels of healthy mothers and their newborns (p < 0.05). No such correlation was found in GDM group (p > 0.05). A significant correlation was found between mother's and newborn's glycemia (p < 0.05) in both groups. CONCLUSION: Suppression of FFA acids in newborn blood of mothers with GDM may represent the lipogenic and antilipolytic activity of the fetus.

Lipids on the Second Day in Ischemic and Normoxemic Term Neonates.

INTRODUCTION: In hypoxic newborns requiring oxygen, lipid peroxidation affects the peripheral blood lipids. OBJECTIVES: Determine the influence of perinatal oxygen therapy for hypoxia on serum lipid concentrations on the second day of life. MATERIALS AND METHODS: Our study included 50 newborns with perinatal hypoxia requiring oxygen and 50 healthy newborns without oxygen therapy. Arterialized capillary blood was taken for categorization of hypoxia (pO2) after birth in both groups. Lipid concentrations: total cholesterol (TC), high density lipoproteins (HDL), low density lipoproteins (LDL), and triglycerides (TG) were measured on day 2 in both groups. RESULTS: TC, LDL, HDL, TG, HC03 levels were statistically lower in the study group compared to the control one, while pCO2 and BE levels were statistically higher in newborns with perinatal hypoxia. CONCLUSION: Lower lipid levels in hypoxic newborns may suggest that circulating lipids are oxidized, peroxidized, and removed from the peripheral circulation.

Mitotic crossover promotes leukemogenesis in children born with TEL-AML1 via the generation of loss of heterozygosity at 12p.

TEL-AML1 (ETV6-RUNX1) fusion gene which is formed prenatally in 1% of the newborns, is a common genetic abnormality in childhood Bcell precursor acute lymphoblastic leukemia. But only one child out of a hundred children born with this fusion gene develops leukemia (bottleneck phenomenon) later in its life, if contracts the second mutation. In other words, out of a hundred children born with TEL-AML1 only one child is at risk for leukemia development, which means that TEL-AML1 fusion gene is not sufficient for overt leukemia. There is a stringent requirement for a second genetic abnormality for leukemia development and this is the real or the ultimate cause of the leukemia bottleneck phenomenon. In most cases of TEL-AML1+ leukemia, the translocation t(12;21) is complemented with the loss of the normal TEL gene, not involved in the translocation, on the contralateral 12p. The loss of the normal TEL gene, i.e. loss of heterozygosity at 12p, occurs postnatally during the mitotic proliferation of TEL-AML1+ cell in the mitotic crossing over process. Mitotic crossing over is a very rare event with a frequency rate of 10-6 in a 10 kb region. The exploration and identification of the environmental exposure(s) that cause(s) proliferation of the TELAML1+ cell in which approximately 106 mitoses are generated to cause 12p loss of heterozygosity, i.e. TEL gene deletion, may contribute to the introduction of preventive measures for leukemia.

Association between pet-keeping and asthma in school children.

BACKGROUND: The role of pet exposure in childhood asthma and allergy is still controversial. The aim of this study was to investigate the association between pet-keeping during different periods of childhood and asthma and sensitization in school children. METHODS: One hundred and forty-nine children aged between 7 and 14 years were enrolled in this study. Seventy-four children had current physician-diagnosed asthma, while 75 children did not have asthma. Pet-keeping was investigated by questionnaire. Allergic sensitization to pet allergen was assessed on skin prick tests and specific serum IgE concentration. Logistic regression analysis was performed, taking into account potential confounders. RESULTS: Early, past and current pet-keeping was not significantly associated with asthma. Neither owning a cat nor dog during childhood was associated with asthma. Early pet-keeping, however, was significantly associated with sensitization to pet allergens (adjusted odds ratio [aOR], 24.11; 95% confidence interval [CI]: 3.28-177.27). Further analysis showed that only early cat-keeping was significantly associated with sensitization to cat allergen (aOR, 51.59; 95%CI: 2.28-1167.07). Keeping a cat or a dog after the first year of life was not associated with sensitization to those allergens. CONCLUSIONS: Keeping a cat or a dog does not increase risk for asthma. Keeping a cat in the first year of life, however, increases risk of sensitization to cat allergen. Considering that this is a relatively small study, larger, prospective, birth cohort studies are required in Serbia to accurately assess the relationship between pet-keeping, asthma and sensitization.

The adjuvant aluminum fate - Metabolic tale based on the basics of chemistry and biochemistry.

Aluminum is inevitable component of many vaccines. The benefit of the vaccines is undeniable but effects of aluminum toxicity might be underestimated and neglected. In this review, we highlighted the mechanims of aluminum toxicity, which is still in debate. So far, all the papers that disscused the adverse aluminum effects pointed two mechanisms responsible for Al toxicity, direct Al toxicity and aluminum induced cell damage via the oxidative metabolism. According to our knowledge, which is based on basic principles of biochemistry and inorganic chemistry, we suggested that aluminum highly interferes with iron metabolism eventually resulting in iron-mediated cell damage. More importantly, in this paper, we offered easily feasible solutions, in order to avoid aluminum toxicity in the future. We suggest that as it once was, Calcium Phosphate again to be used as the adjuvant or better solution that the vaccine adjuvants should be based on zinc compounds or even better would be non-metal adjuvants, such as microcrystalline tyrosine and monosodium urate. Until an adequate adjuvant is provided, we suggest instant postponement of vaccination with vaccines which use aluminum as the adjuvant until the 12 months of age.

Case-control studies compare "apples and pears": Proposal for a retrospective cohort study in the USA of vaccination history in relation to subsequent childhood leukemia.

The role of vaccination in triggering childhood acute lymphoblastic leukemia (ALL) has been assessed in many studies. The results of these studies were found to be inconsistent. The core consistency and significance of all of these studies is the fact that, all these studies were only case-control based. After Greaves' discovery of the prenatal origin of childhood ALL it is perfectly clear that case-control studies compare genetically quite different populations, i.e. "apples and pears". The only way, this genetic shortcoming of case-control studies to be overcome, is simply to replace it by using cohort studies. Cohort studies, has two great shortcomings, the ethics and the lack of statistically sufficient number of unvaccinated children. The first shortcoming could be overcome by using the retrospective variant of cohort studies, whilst the second one by performing these studies in highly populated countries. The country of choice would be the United States of America.

Fatty acids isolated from royal jelly modulate dendritic cell-mediated immune response in vitro.

Royal jelly (RJ), especially its protein components, has been shown to possess immunomodulatory activity. However, almost nothing is known about the influence of RJ fatty acids on the immune system. In this work we studied the effect of 10-hydroxy-2-decanoic acid (10-HDA) and 3,10-dihydroxy-decanoic acid (3,10-DDA), isolated from RJ, on the immune response using a model of rat dendritic cell (DC)-T-cell cocultures. Both fatty acids, at higher concentrations, inhibited the proliferation of allogeneic T cells. The effect of 10-HDA was stronger and was followed by a decrease in interleukin-2 (IL-2) production and down-regulation of IL-2 receptor expression. Spleen DC, cultivated with 10 microg/ml of fatty acids down-regulated the expression of CD86 and the production of IL-12, but up-regulated the production of IL-10. In contrast, DC, pretreated with 100 microg/ml of 3,10-DDA, up-regulated the expression of CD86 and augmented the proliferation of allogeneic T cells. The highest dose (200 microg/ml) of both fatty acids which was non-apoptotic for both T cells and DC, down-regulated the expression of MHC class II and CD86, decreased the production of IL-12 and made these DC less allostimulatory. The immunosuppressive activity of 3,10-DDA was also confirmed in vivo, using a model of Keyhole lymphet hemocyanine immunization of rats. In conclusion, our results showed the immunomodulatory activity of RJ fatty acids and suggest that DC are a significant target of their action.

Childhood acute lymphoblastic leukemia is triggered by the introduction of immunization against diphtheria.

BACKGROUND: Childhood acute lymphoblastic leukemia has prenatal origin. Leukemogenic translocations originating during fetal life are insufficient for overt leukemia. Transgenic TEL-AML1 mice have failed to develop leukemia. Additional postnatal events are required for full leukemogenesis. The significant peak-age (2-5 years) first appeared after 1940 in Great Britain. Since then, childhood leukemia has almost unchangeable incidence. In 1940 the introduction of immunization against diphtheria on a national scale was begun in Great Britain. HYPOTHESIS: Childhood acute lymphoblastic leukemia is triggered by vaccination against diphtheria. TESTING THE HYPOTHESIS: Epidemiological survey for leukemia cases among "exemptors" and unvaccinated cases among ALL children should be done. Simultaneously, the transgenic TEL-AML1 mice should be vaccinated with the diphtheritic toxoid. IMPLICATIONS OF THE HYPOTHESIS: If there is no leukemia among the "exemptors", no unvaccinated among ALL, and some mice develop leukemia upon vaccination childhood leukemia will be prevented by massive neonatal screening for leukemogenic genetics and/or with a new vaccination schedule.

Are xenogeneic anti-tissue transglutaminase antibodies the holy grail for celiac patients?

Celiac disease is an immune mediated disorder, the only one with a well-established origin, resulting from a permanent gluten intolerance. Although a gluten-free diet is currently the "safe" and appropriate therapy for celiac disease, this is not always an easy and simple option as "harmful" gluten may contaminate food during the processing and preparation phases. There are also further social pressures, which might be more pressing for young celiac patients, in following a strict gluten-free diet. Therefore, a new therapeutic approaches are sought which would permit celiacs to "peacefully" coexist with gluten. Presently, the most promising looks search for genetically modified wheat lacking toxic gluten peptides and the use of oral endopeptidases in attempt to curb gluten toxicity. Recently discovered role of anti-tissue transglutaminase antibodies in celiac pathogenesis has brought a prospect for a new hypothetical therapeutic approach, an oral immunization of celiacs with xenogeneic anti-tissue transglutaminase antibodies.

Metabolically based liver damage pathophysiology in patients with urea cycle disorders - A new hypothesis.

The underlying pathophysiology of liver dysfunction in urea cycle disorders (UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle (UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs. Owing to our routine clinical practice to screen for iron overload in severely ill neonates, with the focus on the newborns suffering from acute liver failure, we report a case of citrullinemia with neonatal liver failure and high blood parameters of iron overload. We hypothesize that the key is in the decreased-deficient fumaric acid production in the course of UC in UCDs that causes several sequentially intertwined metabolic disturbances with final result of liver iron overload. The presented hypothesis could be easily tested by examining the patients suffering from UCDs, for liver iron overload. This could be easily performed in countries with a high population and comprehensive national register for inborn errors of metabolism. CONCLUSION: Providing the hypothesis is correct, neonatal liver damage in patients having UCD can be prevented by the supplementation of pregnant women with fumaric or succinic acid, prepared in the form of iron supplementation pills. After birth, liver damage in patients having UCDs can be prevented by supplementation of these patients with zinc fumarate or zinc succinylate, as well.

Wiskott-Aldrich syndrome with macrothrombocytopenia.

BACKGROUND: Wiskott-Aldrich syndrome is a rare X-linked immunodeficiency disorder with a variable phenotype. CASE CHARACTERISTICS: 3.5-year-old boy diagnosed with Wiskott-Aldrich syndrome. OBSERVATION: Unusual and persistent thrombocytopenia with increased platelet volume (>10fL). He did not exhibit characteristic clinical and laboratory finding for the syndrome. OUTCOME: Maternally inherited causative mutation in the exon 2 of the WAS gene was disclosed. MESSAGE: This is a need for multidisciplinary assessment of patients with congenital or early infantile thrombocytopenia, including testing for mutations of the WAS gene in all unexplained cases even in the absence of characteristic microthrombocytopenia.

Mitotic crossover--an evolutionary rudiment which promotes carcinogenesis of colorectal carcinoma.

Mitotic crossover is a natural mechanism that is a main source of the genetic variability of primitive organisms. In complex organisms such as mammals, it represents an evolutionary rudiment which persisted as one of the numerous DNA repair mechanisms, and results in the production of homozygous allele combinations in all heterozygous genes located on the chromosome arm distal to the crossover. This event is familiar as loss of heterozygosity, which is one of the key mechanisms responsible for the development and progression of almost all cancers. We propose the hypothesis in which mitotic crossover is a principal source of the increased loss of heterozygosity that leads to the initiation and progression of colorectal carcinoma. The hypothesis could be tested by in vitro inhibition of Rad51 protein, orthotopic grafting of human colon cancer tissue into the gut of mice, and treatment with potential inhibitors. After these procedures, the frequency of mitotic crossover would be estimated. The development of selective inhibitors of mitotic crossover could stop further carcinogenesis of colorectal carcinoma, as well as many other neoplastic events. Loss of heterozygosity is an event responsible for carcinogenesis, its reduction by selective inhibitors of mitotic crossover could have a positive effect on cancer chemoprevention, as well as on growth reduction and a cessation in the progression of earlier developed tumors.

Childhood leukemia genetic bottleneck phenomenon related to TEL-AML1: the postulation by a mathematical model.

Childhood leukemia bottleneck phenomenon is the most mysterious corollary of the prenatal origin discovery of leukemogenic chromosome translocations. The bottleneck is evidence that leukemia initiation, by in utero acquired chromosome translocations that generate functional fusion genes, is far more common than the incidence rate of corresponding leukemia. For childhood TEL-AML1(+) acute lymphoblastic leukemia (ALL) this equates to approximately 100 times. Practically this means that among a hundred children born with TEL-AML1 fusion gene, only one child will later in its life develop ALL. The key data necessary for unraveling of this mystery were discovered in 2002. It was the level of TEL-AML1(+) cells' frequency. The bottleneck is caused by the very low body TEL-AML1(+) cell count. Only one out of a thousand B cells carries TEL-AML1 fusion gene. TEL-AML1(+) body cell count is low because TEL-AML1 fusion is generated at cell level of 10(-3) to 10(-4) just during the late fetal lymphopoiesis i.e. after the 36th gestational week.

Childhood-onset myasthenia gravis with thymoma.

Juvenile myasthenia gravis is an acquired, autoimmune disease occurring before age 16 years. Thymoma is exceedingly rare in children, especially in association with juvenile myasthenia gravis. We describe a 14-year-old boy with juvenile myasthenia gravis and thymoma. He presented with difficulties chewing and swallowing, nasal speech, and fluctuating weakness of the leg muscles. Neurologic examination revealed masticatory and bulbar muscle weakness with nasal speech, proximal muscle weakness, fatigability of the arms and legs, and distal muscle weakness of the legs. A diagnosis of juvenile myasthenia gravis was confirmed by a positive neostigmine test, a decremental response on repetitive nerve stimulation, and increased titers of serum anti-acetylcholine receptor antibodies. The patient received anticholinesterases, corticosteroids, azathioprine, and thymectomy. A pathohistologic analysis of the thymus gland indicated thymoma, Masaoka grade II. After 2 years of an unstable disease course, remission was achieved. Because only 10 cases of thymoma-associated myasthenia gravis are described in the pediatric population, this report offers an important contribution to a better understanding of this rare association.

[Evaluation of psycho-motor development in children with West syndrome].

INTRODUCTION: West Syndrome (WS) is age-related epileptic encephalopathy characterised by a triad of symptoms: specific seizure type, pathognomonic electroencephalographic (EEG) pattern--hypsarrhythmia and delay and/or regression in psychomotor development (PMD). Aetiologically, it occurs in three forms: symptomatic, cryptogenic and idiopathic. OBJECTIVE: Estimation of PMD in children with WS according to aetiology. METHODS: The observed group consisted of 65 children. Age range was between 6 and 30 months. The patients were divided into three groups according to aetiology. All patients underwent psychological examination with Brunet-Lesine test, as well as PMD evaluation based on achieved developmental milestones for the corresponding age. RESULTS: Statistically significant better values in the Human Developmental Index (HDI) had patients with idiopathic compared to otherforms of WS, at testing after 12 months (93.0 +/- 8.1 vs. 46.8 +/- 6.1 vs. 45.6 +/- 3.8), as well as after 24 months (93.9 +/- 7.7 vs. 51.9 +/- 5.5 vs. 50.9 +/- 4.4). The best values of HDI after 24 months had patients with improvement in PMD with the average of 66.2 +/- 4.4, which was statistically significant compared to those with unchanged PMD (41.5 +/- 5.3) and with further regression in PMD (28.3 +/- 4.4). Significant correlation was obtained between PMD after 12 and 24 months (r = 0.477), as well as a considerable improvement in HDI from the 12th to 24th month (49.4 +/- 4.0 vs. 53.7 +/- 3.9). CONCLUSION: The patients with idiopathic WS accomplished the best PMD. Improvement in PMD after 12 and 24 months of treatment was associated with improved HDI. Improvement in PMD was observed in all patients after 2 years of follow-up.

Erythrocytic transglutaminase inhibition hemolysis at presentation of celiac disease.

Celiac disease (CD) is a common autoimmune condition. Previously it was considered to be a rare childhood disorder, but is actually considered a relatively common condition, present at any age, which may have multiple complications and manifestations. Hematological disorders of the disease are not uncommon. Among these disorders, the most frequently reported are anemias as a result of iron deficiency, often associated with folate and/or B12 deficiency. Anemias caused by hemolysis are very rarely reported in celiac patients. An 11-year-old girl with a previous uneventful medical history presented with severe hemolytic anemia. Hemolysis was Coombs negative, accompanied by inappropriate low reticulocyte count, despite exaggerated bone marrow hyperplasia of the erythroid precursors which showed normal maturation. Serology for recent infections, including Epstein-Barr virus, parvovirus B19, cytomegalovirus and mycoplasma, were all negative. Levels of serum IgA, IgG and IgM, were all within normal ranges for age. Screening for anti-DNA, antinuclear, antineutrophil cytoplasmic, antimicrosomal, antithyroglobulin, and antimitochondrial antibodies and lupus anticoagulants, was negative. She was also negative for human immunodeficiency virus. Conventional therapy with corticosteroids and intravenous immunoglobulin failed. CD was serendipitously discovered upon screening for anti-tissue transglutaminase autoantibodies. The disease was confirmed by biopsy of the small intestine mucosa. The patient recovered with gluten-free diet. A unique case of CD is presented. CD should be serologically screened in each patient with Coombs negative "immune" hemolytic anemia, particularly if accompanied by "reticulocytopenia". A new hemolytic mechanism and very speculative explanation for "reticulocytopenia" are discussed.

Intraoperative anaphylactic shock in a child with no history of type I hypersensitivity.

Natural rubber latex is the second most implicated agent in intraoperative anaphylactic reactions. This report describes a case of intraoperative anaphylaxis occurring in a non-atopic fourteen-year-old girl undergoing multiple surgical procedures, but without spina bifida, in which latex surgical gloves were the main culprit for the anaphylactic reactions. Clinical manifestations of an anaphylactic reaction were also experienced during the examination of the possible cause of intraoperative anaphylaxis by skin prick testing with a latex allergen extract. Skin tests with anesthetics were negative. Specific IgE to latex was positive at 92.9 kUA/L (class 5). The molecular basis for the reported intraoperative anaphylaxis was ascribed to three low-molecular mass latex allergens (10-15 kD) detected in the brand of latex surgical gloves used during the operation. Given the potential of a dramatic outcome, latex allergy testing as a regular preoperative measure may contribute to the reduction of anaphylactic reactions during surgical interventions.