10-year experience with umbilical cord blood IgE and microbiome therapy.

BACKGROUND: The benefit of probiotics in newborn children in relation to allergy and general morbidity later in life appears to be controversial. Allergic diseases represent an increasingly important health problem worldwide in recent years. This is evident in all age groups. The occurrence of allergic illnesses also continues to rise exponentially, and thus the use of preventive and prognostic methods, particularly in children with an inherently higher risk of allergy, is gaining increased importance. Since the advent of probiotics the effect of probiosis on immunity through alterations of composition and function of the human gut microbiome has been increasingly studied. The exact mechanisms have not yet been clearly defined. The Academy of Sciences of the Czech Republic (The Czech Academy of Sciences has suggested that the expression of TH1 and TH2 cytokines in umbilical blood is associated with an increased risk of allergies. The counter -balance of Th1 and Th2 affect Immunoglobulin E (IgE) production and maturation of the gastrointestinal tract epithelium. CASE PRESENTATION: We examined IgE levels in 3000 samples of umbilical blood taken from children born into families with a positive history of allergy in one or both parents from 2007 to 2017. At the age of ten days, those with high IgE were given Colinfant Newborn (a lyophilized non-pathogenic strain of Escherichia.coli) for one month, three times weekly. At 15 months and three years we investigated the levels of Immunoglobulins E,A and G, and the incidence of illness and allergy. The results revealed that allergy and high umbilical IgE is strongly linked with family history (p ≤ 0.001). We also detected differences in seasonality, especially with regards to pollen allergies. Eighty percent of children treated with Colinfant Newborn had significantly reduced IgE and morbidity at 13-15 months and 3 years, and furthermore without any clinical signs of allergy. Normalization of Immunoglobulins A and G was seen in 90% of treated subjects (p ≤ 0.001). These levels significantly correlated with an almost negligible morbidity up to 4 years of life. Colinfant Newborn, a lyophilized strain of Esherichia coli (E. coli), and a normal component of intestinal flora, readily colonizes the intestinal tract. It's long term presence significantly stimulates the production of specific and non-specific intestinal antibodies. and optimalizes immune development through tolerance. In our study Colinfant Newborn reduced the incidence of infections later in life by safely and effectively normalizing immunoglobulin levels in the majority of treated patients. CONCLUSION: Our study strongly suggests as positive effect of physiological Escherichia coli on the microbiome of newborn children as evidenced by a significantly reduced incidence of allergy and morbidity when applied early in life. These benefits appear to be strongly strain specific.

Possible etiology and treatment of amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is one of the most dangerous and least understood diseases with a pathophysiology that is still largely unknown. In this article we try to provide a pathophysiological explanation of the etiological, pathogenetic, and clinical aspects of ALS. After a description of the rather complicated classification of the disease, we continue with an evaluation of its clinical presentation. The bibliography reveals several suspect etiological factors including atherosclerosis, inflammation, tumors, cataracts, diabetes mellitus type 2, aging, and degeneration of the nervous system. One of the more intriguing factors involves changes associated with oxidative damage to both neurons and glial cells. It is known that astrocytes support the development of motor neurons. Oxidative damage is known to lead to the expression of stress sensitive genes, proteins, as well as inflammation of glial cells. Chronic inflammation could be a key factor in ALS since it has been linked to the death of motor neurons. Pathophysiological research has confirmed the influence of certains proteins on the prognosis of ALS. ALS is typically a proteinopathy in which proteins aggregate in motoneurons. Additionally, glutamate excitotoxicity has also been linked to ALS, with mutated superoxide dismutase (SOD1) having been shown to be responsible for familial ALS. As concerns the pathogenesis of ALS, we discussed several phenomenon such as increased levels of specific serum compounds, reduced concentrations of myelin, and changes in 5-hydroxytryptamine that could represent key indicators of the pathogenesis, prognosis, and therapy of ALS. Concerning ALS therapy; treatment with antioxidatives is potentially very important. Exposure to heavy metals is also thought to negatively influence ALS. Evidence also suggests that good nutrition is a very important factor in the treatment of ALS. From a pharmacological perspective, serotonin treatment appears to be a useful therapeutic agent.

The evaluation of nociceptive intensity by using free radicals direct measurement by EPR method in the tail of anaesthetized rats.

OBJECTIVES: The aim of the study was to demonstrate the ability to measure free radicals and singlet oxygen, using EPR methods, in the tail of anaesthetized rats. The advantage of this method lies in the potential for continuous evaluation of free radicals and singlet oxygen during nociceptive processes. METHODS: Electron paramagnetic (spin) resonance (EPR/ESR) was used. DMPO and PBN as spin traps and thermal mechanical pulp (TMP) as a spin detector of singlet oxygen were used. Thirty-one adult male (Wistar) rats were used for the experiments. They were housed according to principles of good laboratory practice. The animals were stimulated for 10 minutes on 5 consecutive days by using clamps on the hind limbs. During the EPR measurement they were anaesthetized with a mixture of ketamine and xylazine. Hydroxyl and nitroxide free radicals, as well as singlet oxygen were measured. RESULTS: After nociceptive stimulation, free hydroxyl radicals were increased as well as free nitroxide radicals. Singlet oxygen was also increased after nociceptive stimulation. Antioxidants significantly decreased the increase in hydroxyl radicals after nociceptive stimulation. CONCLUSIONS: Our results confirmed an increase in free radicals and singlet oxygen after nociceptive stimulation and a reduced increase after application of antioxidants. Direct EPR methods were first used in the tail of anaesthetized rats and represent an extremely useful tool for the evaluation of pain intensity in living animals.

Direct measurement of free radicals in the brain cortex and the blood serum after nociceptive stimulation in rats.

The concentrations of ROS were measured in samples of the sensorimotor brain cortex and in the rat blood. We measured the following parameters: The six lines spectra, nitroxide radical, free hydroxyl radical and singleton oxygen. Their concentration was measured under physiological conditions, after the nociceptive stimulation and after the application of melatonin, both in normal and stimulated animals. In the brain cortex only the singleton oxygen decreased after the nociceptive stimulation, whereas the nitroxide radicals and six lines spectra increased. The free hydroxyl radicals did not change significantly. In the blood serum the six lines spectra and nitroxide radical increased, the concentration of the free hydroxyl radicals did not change. Melatonin increased both the hydroxyl and nitroxide radicals. There was a non-significant decrease in the six lines spectra. The estimation of ROS can be used as a tool for detecting metabolic changes and the consequences of different environmental influences, in our case the influence of nociception and melatonin.

Free radicals after painful stimulation are influenced by antioxidants and analgesics.

OBJECTIVES: To study the balance between the pro-oxidative and antioxidative defence system after repeated painful stimulation in rats and the efficacy of the administration of different antioxidants (vitamins C, E, A, and selenium), analgesics (acetylsalicylic acid, morphine), and their combinations. METHODS: Mechanical clamping of both hind limbs was applied for 10 min for 5 consecutive days in adult male Wistar rats. The tail-flick latency was measured before and after a 5-day nociceptive stimulation with or without the substance application. The reactive oxygen species (ROS) were determined in the sensorimotor cortex. RESULTS: Painful stimulation increased lipoperoxidation which persisted for up to 15 days after it had been discontinued. A simultaneous injection of antioxidants decreased the levels of TBARS, SOD and GSHPx; however, antioxidants applied one week prior to the painful stimulation were ineffective. A simultaneous injection of analgesics reduced stress-induced analgesia caused by the nociceptive stimulation, but did not affect lipoperoxidation. CONCLUSIONS: A combination of antioxidants with analgesics normalized both the oxidative stress and functional (the tail-flick latency) indicators. These results suggest that the administration of antioxidants in pain treatment may be employed to decrease the doses of analgesics and to prevent the negative impact of reactive oxygen species on nociception.