6,7,4[Formula: see text]-Trihydroxyflavanone Prevents Methamphetamine-Induced T Cell Deactivation by Protecting the Activated T Cells from Apoptosis.

Methamphetamine (METH) is an extremely addictive drug that has raised serious public health concerns recently. METH addiction not only results in neuronal cytotoxicity, but it also affects immune cell activity, including T lymphocytes. 6,4,7[Formula: see text]-trihydroxyflavanone (THF), isolated from Dalbergia odorifera, has been studied for its antibacterial activity, but evidence for whether THF has an anti-cytotoxic and protective effect on T cell activation exposed to METH is lacking. In this study, results showed that treatment with THF was not cytotoxic to Jurkat T cells but dose-dependently mitigated the cytotoxicity induced by exposure to METH. The Western blot results demonstrating pre-treatment with THF maintained the expression of anti-apoptotic proteins and phosphorylation of PI3K/Akt/mTOR downregulated by treatment with METH. Furthermore, we found that decreased expression of IL-2 and CD69 by METH exposure was partially restored, and viability was significantly prevented by pre-treatment with THF in activated T cells. These findings were involved in re-elevated expression of anti-apoptotic proteins as well as recovered pathways including MAPK/PI3K/Akt/mTOR in activated T cells pre-exposed to METH. Our results suggest beneficial effects of THF against the cytotoxic and immune-modulating effect of METH on T cells and therapeutic potential of THF for patients with immunodeficiency caused by METH addiction.

A systematic literature review of the effects of immunoglobulin replacement therapy on the burden of secondary immunodeficiency diseases associated with hematological malignancies and stem cell transplants.

INTRODUCTION: Secondary immunodeficiency diseases (SID) caused by hematological malignancies (HMs), stem cell transplant (SCT), and associated therapies are mainly characterized by the presence of hypogammaglobulinemia or antibody production deficits. AREAS COVERED: The authors summarized the scientific literature on disease burden of SIDs in patients who had HMs or SCT. Systematic searches were conducted to identify English-language articles from 1994-2020, reporting on clinical, humanistic, and economic burdens of SID due to HMs or SCT. Definitions of SID and serum immunoglobulin G thresholds varied across 24 eligible studies. In most (n = 16) studies, patients received immunoglobulin replacement therapy (IGRT). Several studies found IGRT was associated with significant reductions in rates of infection and antimicrobial use. However, 1 study found no statistically significant difference in antibiotic use with IGRT. Only 3 studies reported on quality of life, and no economic studies were identified. EXPERT OPINION: Overall, the findings show several beneficial effects of IGRT on clinical outcomes and quality of life; however, disparate definitions, infrequent reporting of statistical significance, and scarcity of clinical trial data after the 1990s present areas for further investigation. This paucity indicates an unmet need of current evidence to assess the benefits of IGRT in SID.

Invasive meningococcal disease in patients with complement deficiencies: a case series (2008-2017).

BACKGROUND: To describe patients with inherited and acquired complement deficiency who developed invasive meningococcal disease (IMD) in England over the last decade. METHODS: Public Health England conducts enhanced surveillance of IMD in England. We retrospectively identified patients with complement deficiency who developed IMD in England during 2008-2017 and retrieved information on their clinical presentation, vaccination status, medication history, recurrence of infection and outcomes, as well as characteristics of the infecting meningococcal strain. RESULTS: A total of 16 patients with 20 IMD episodes were identified, including four with two episodes. Six patients had inherited complement deficiencies, two had immune-mediated conditions associated with complement deficiency (glomerulonephritis and vasculitis), and eight others were on Eculizumab therapy, five for paroxysmal nocturnal haemoglobinuria and three for atypical haemolytic uraemic syndrome. Cultures were available for 7 of 11 episodes among those with inherited complement deficiencies/immune-mediated conditions and the predominant capsular group was Y (7/11), followed by B (3/11) and non-groupable (1/11) strains. Among patients receiving Eculizumab therapy, 3 of the 9 episodes were due to group B (3/9), three others were NG but genotypically group B, and one case each of groups E, W and Y. CONCLUSIONS: In England, complement deficiency is rare among IMD cases and includes inherited disorders of the late complement pathway, immune-mediated disorders associated with low complement levels and patients on Eculizumab therapy. IMD due to capsular group Y predominates in patient with inherited complement deficiency, whilst those on Eculizumab therapy develop IMD due to more diverse capsular groups including non-encapsulated strains.

Role of nutrition on anemia in elderly.

Anemia in elderly population have a great incidence and is related to increased mortality risk. The incidence of nutrition in anemia is about one third of the total. Caloric and protein restriction, iron, vitamin B12, folic deficiency are the causes of nutritional anemia. Protein and energy malnutrition stimulate an increased cytokines production with induction of inflammation, immunodeficiency and anemia. Anorexia and obesity can be associated with anemia due to increased cytokines and hepdicin serum level. Macrophages activity is inhibited and a decrease in red blood cells (RBC), hemoglobin (Hb) concentration due to ineffective erythropoiesis is observed. An adequate energy and protein diet is necessary to reduce inflammation and increase iron absorption. A minimum of 1700 kcal/day and 1.7 gr/kg/day of protein intake are necessary to maintain anabolism in chronic patients to prevent and treat anemia. Iron supplementation by intravenous injection is safe and effective to correct severe iron deficiency. The supplementation of vitamins and oligomineral are useful to reduce oxidative stress and improve RBC longevity. Anemia in elderly could be prevented by an adequate nutrition, a simple and not expensive intervention, and associated to physical exercise reduce the incidence of mortality rate.

HemoHIM ameliorates the persistent down-regulation of Th1-like immune responses in fractionated γ-irradiated mice by modulating the IL-12p70-STAT4 signaling pathway.

Whole body irradiated mice appear to experience a down-regulation of the helper T (Th)1-like immune response, and maintain a persistent immunological imbalance. In the current study, we evaluated the effect of HemoHIM (an herbal product made from Angelica Radix, Cnidium officinale , and Paeonia japonica cultivated in Korea) to ameliorate the immunological imbalance induce in fractionated γ-irradiated mice. The mice were exposed to γ rays twice a week (0.5 Gy fractions) for a total dose of 5 Gy, and HemoHIM was administrated orally from 1 week before the first irradiation to 1 week before the final analysis. All experiments were performed 4 and 6 months after their first exposure. HemoHIM ameliorated the Th1- and Th2-related immune responses normally occur in irradiated mice with or without dinitrophenylated keyhole limpet hemocyanin immunization. HemoHIM also restored the natural killer cell activities without changing the percentage of natural killer cells in irradiated mice. Furthermore, the administration of HemoHIM prevented the reduction in levels of interleukin-12p70 in irradiated mice. Finally, we found that HemoHIM enhanced the phosphorylation of signal transducer and activator of transcription (STAT) 4 that was reduced in irradiated mice. Our findings suggest that HemoHIM ameliorates the persistent down-regulation of Th1-like immune responses by modulating the IL-12p70/pSTAT4 signaling pathway.

Vitamin A supplementation in late pregnancy can decrease the incidence of bronchopulmonary dysplasia in newborns.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of infancy which is associated with prematurity and early lung injury resulting from mechanical ventilation. Oxygen toxicity, barotrauma, and volutrauma play key roles in its pathogenesis. Parenteral administration of Vitamin A to the newborn is the current recommended preventive therapy for BPD. Vitamin A has been found to upregulate genes necessary for fetal lung growth and increase surfactant production in animal models. Supplementation of Vitamin A in late pregnancy increases the cord blood vitamin A levels proportionately. Hence, we hypothesize that Vitamin A supplementation during late pregnancy can decrease the incidence of BPD in newborns. This can be an effective adjunct to postnatal preventive therapy. Vitamin A supplementation in late pregnancy carries no risk of teratogenicity unlike in early pregnancy. Moreover, vitamin A deficiency in pregnancy is associated with depressed immune function leading on to increased infectious morbidity and can cause intrauterine growth retardation, low birth weight and anemia in newborns. Combining antenatal Vitamin A supplementation to the mother with postnatal supplementation to the newborn can effectively prevent BPD better than the traditional postnatal preventive therapy alone. It will also treat the highly prevalent vitamin A deficiency in pregnant mothers and newborns of the developing world.

Effect of glycine on the immune response of the experimentally diabetic rats.

BACKGROUND: Hyperglycemia induces protein glycation, disturbing its function, additionally, the glycated products (AGEs) induce by themselves proinflammatory cytokine release that are responsible for insulin resistance. Glycine has been successfully used in diabetic patients to competitively reduce hemoglobin glycation. OBJECTIVES: To assess hyperglycemia impact on the immune response and to evaluate if it is possible to reverse it by means of glycine administration. MATERIAL AND METHODS: Streptozotocin-induced diabetic rats, with and without glycine administration were challenged with sheep red blood cells, and specific antibody producing cells were accounted. Normal rats were challenged as controls. RESULTS: Induced diabetes modifies significantly the humoral immune response capacity versus sheep red blood cells. Also, glycine administration prevents against this deleterious effect. CONCLUSIONS: Glycine could be an important therapeutic resource among diabetics to avoid the characteristic immunodeficiencies of this disease.

[Enterosorption and nutritious support with pectin-containing preparation in the treatment of stress immunodeficiency in peritonitis].

Fifty-eight patients aged from 18 to 65 years with peritonitis of different etiology in toxic and terminal phases were treated. Nasoenteral intubation, enterosorption and early nutritious support with pectin-containing preparation (PCP) were carried out in all the patients just after surgery with standard course of 5 days. Baseline data was compared with that after PCP-supported treatment. Powder products of red beet were used as PCP. Immunodeficiency in peritonitis is characterized by imbalance of stress-realizing and stress-limiting mechanisms of immunocompetent cells. Enterosorption and early nutritious support with PCP in peritonitis decrease the level of plasmic cortisol and enhance stress-limiting reception that reduces a harmful effect of cortisol and reestablishes immunity.

Active hexose correlated compound enhances the immune function of mice in the hindlimb-unloading model of spaceflight conditions.

Hindlimb unloading is a ground-based model that simulates some of the aspects of spaceflight conditions, including lack of load bearing on hindlimbs and a fluid shift to the head. It has been shown that treatment with active hexose correlated compound (AHCC) restores resistance to infection in mice maintained under hindlimb-unloading conditions. The present study was designed to clarify the mechanisms by which AHCC enhances resistance to infection in this model. We hypothesized that oral administration of AHCC will enhance the function of the immune system, which could lead to the increased resistance to infection observed in this model. AHCC or the excipient was orally administered to mice, and the function of the immune system was assessed in spleen and peritoneal cells isolated from those groups. The results of the present study showed that administration of AHCC for 1 wk before and throughout the second day of the hindlimb-unloading period enhanced the function of the immune system assessed by spleen cell proliferation and cytokine production in spleens and nitric oxide and cytokine production in peritoneal cells. These findings suggest that AHCC can be used as a potent immunoenhancer, especially in cases in which the immune system is suppressed by any condition, including diseases such as human immunodeficiency virus infection and cancer.

Cortisol abnormality as a cause of elevated estrogen and immune destabilization: insights for human medicine from a veterinary perspective.

For more than 35 years the author has treated multiple serious diseases in cats and dogs by correcting an unrecognized endocrine-immune imbalance originating with a deficiency or defect of cortisol. The cortisol abnormality creates a domino effect on feedback loops involving the hypothalamus-pituitary-adrenal axis. In this scenario, estrogen becomes elevated, thyroid hormone becomes bound, and B and T cells become deregulated. Diseases with this aberration as a primary etiological component range from allergies to severe cases of autoimmunity to cancer. The author has consistently identified excess estrogen or "estrogen dominance" as part of an endocrine-immune derangement present in many common diseases of dogs and cats. Ninety-percent of these cases involve spayed females and neutered or intact males, so the elevated estrogen cannot be attributed to ovarian activity. The author identifies the adrenal cortex as a source of the imbalance, which produces a variety of vital hormones. The author has developed an endocrine-immune blood test that measures cortisol, total estrogen, T3 and T4, and IgA, IgG, and IgM antibody levels. The protocol for corrective therapy involves the use of various cortisone medications, either standard pharmaceutical compounds or a natural bio-identical preparation made from an ultra extract of soy. The author's clinical success and the growing clinical applications of low-dosage cortisone therapy for humans strongly argue for sustained research into the nature, magnitude, and impact of cortisol defects, including an associated estrogen-immune problem, in the etiology of disease.

Immunodeficiency and cancer: prospects for correction.

Cellular immunodeficiency is associated with human cancer. Extensive reviews on cancer of the head and neck, lung, esophagus and breast convince the author that for these diseases the immunodeficiency is reasonably well established yet the mechanisms are poorly understood. Evidence indicates that other tumors are similarly associated with cellular immune deficiency. The advent of recombinant cytokines and of antitumor monoclonal antibodies has served to focus attention toward direct tumoricidal mechanisms. As tumor antigens relating to cellular and humoral immune mechanisms are being defined and vaccine strategies are increasingly being attempted, it is critical to confront issues of the mechanism of anergy and effective immunorestoration in order to maximize the potential of cellular immune response to address these tumor antigens. Intrinsic to this approach is the introduction of contrasuppressive therapy to alleviate the tumor-associated immune suppression. Encouraging attempts have been made with plasmapheresis, indomethacin, low-dose cyclophosphamide, anti CTLA-4, anti FAS ligand and, perhaps in the future, more judiciously applied chemotherapy. In contrast to the popular notion that thymic involution cannot be reversed in the adult, studies from the author's laboratory indicate that in aged hydrocortisone stressed mice, a natural Type 1-cytokine mixture (IRX-2) hastens the reversal of thymic involution and promotes T-cell responses to cytokines and mitogens. Recombinant IL-1 and IL-2 by themselves, and in combination, were inactive. Similar positive effects were observed with oral zinc, zinc-thymulin and thymosin alpha(1). The combination of a natural cytokine mixture (IRX-2) with thymosin alpha1 had a very large effect and increased the absolute number of peripheral T lymphocytes as measured in the spleen. In studies of combination immunotherapy in lymphocytopenic squamous cell head and neck cancer patients using IRX-2 (18 patients) and IRX-2 plus thymosin alpha(1) (IRX-3) in IRX-2-refractory patients (7 patients), marked increases in CD(45)RA(+) 'naïve' T cells (>250/mm(3)) were observed. These are among the first insights into how to generate T lymphocyte replacement in the adult. These and many other experimental efforts point to ways to achieve more effective immunotherapy of human cancer in the future, particularly if tumor-induced immune deficiency can be effectively addressed.

Pathogenetic aspects of immune deficiency associated with beta-thalassemia.

Infectious complications constitute the second most common cause of mortality and a main cause of morbidity in beta-thalassemia. Besides the high risk of blood-borne infections associated with multiple transfusions, the increased susceptibility of these patients to infectious diseases has been attributed to a coexistent immune deficiency. Immune abnormalities have also been held responsible for the frequent occurrence of malignancies in beta-thalassemia, especially leukemia and lymphomas. Recent studies on immune competence in beta-thalassemia have revealed numerous quantitative and functional defects, involving T and B lymphocytes, immunoglobulin production, neutrophils and macrophages, chemotaxis, and phagocytosis, as well as the complement system. Regarding pathogenesis, iron overload, a primary complication of both thalassemia itself and transfusion therapy, is thought to be the main precipitating mechanism, due to the important immunoregulatory properties of iron and its binding proteins; iron excess may derange the immune balance in favor of the growth of infectious organisms. Other factors include multiple transfusions, associated with constant allo-antigenic stimulation, as well as with transmission of immunosuppressive viruses; splenectomy, resulting in increased susceptibility to infections by encapsulated bacteria and to immune system modifications; low levels of zinc, another immune regulator; iron chelation therapy, which predisposes to serious infections by yersinia species; and the circulation of abnormal native thalassemic erythrocytes, forming another permanent immune stimulus. Thus surveillance for infections in patients with beta-thalassemia is crucial, while further studies are warranted on immune function abnormalities and the implicated mechanisms.

Magnesium-DNA interactions and the possible relation of magnesium to carcinogenesis. Irradiation and free radicals.

Magnesium deficiency causes renal complications. The appearance of several diseases is related to its depletion in the human body. In radiotherapy, as well as in chemotherapy, especially in treatment of cancers with cis-platinum, hypomagnesaemia is observed. The site effects of chemotherapy that are due to hypomagnesaemia are decreased using Mg supplements. The role of magnesium in DNA stabilization is concentration dependent. At high concentrations there is an accumulation of Mg binding, which induces conformational changes leading to Z-DNA, while at low concentration there is deficiency and destabilization of DNA. The biological and clinical consequences of abnormal concentrations are DNA cleavage leading to diseases and cancer. Carcinogenesis and cell growth are also magnesium-ion concentration dependent. Several reports point out that the interaction of magnesium in the presence of other metal ions showed that there is synergism with Li and Mn, but there is magnesium antagonism in DNA binding with the essential metal ions in the order: Zn>Mg>Ca. In the case of toxic metals such as Cd, Ga and Ni there is also antagonism for DNA binding. It was found from radiolysis of deaerated aqueous solutions of the nucleoside 5'-guanosine monophosphate (5'-GMP) in the presence as well as in the absence of magnesium ions that, although the addition of hydroxyl radicals (*OH) has been increased by 2-fold, the opening of the imidazole ring of the guanine base was prevented. This effect was due to the binding of Mg2+ ions to N7 site of the molecule by stabilizing the five-member ring imitating cis-platinum. It was also observed using Fourier Transform Infrared spectroscopy, Raman spectroscopy and Fast Atom Bombardment mass spectrometry that *OH radicals subtract H atoms from the C1', C4' and C5' sites of the nucleotide. Irradiation of 5'-GMP in the presence of oxygen (2.5 x 10(-4) M) shows that magnesium is released from the complex. There is spectroscopic evidence that superoxide anions (O2-*) react with magnesium ions leading to magnesium release from the complex. From radiolysis data it was suggested that magnesium ions can act as radiosensitizers in the absence of oxygen, while in the presence of oxygen they act as protectors and stabilizers of DNA.

Immunonutrition--supplementary amino acids and fatty acids ameliorate immune deficiency in critically ill patients.

BACKGROUND: Immunonutrition with omega-3 fatty acids and the "conditionally essential" amino acids arginine, glutamine, cysteine, and taurine can enhance the immune response in critically ill patients. This is due to the immunomodulating properties of these nutrients. Immunonutrition is especially important when a patient's immune response is compromised, as is the case post-operatively or after trauma. Immune deficiency is severely aggravated in sepsis and the systemic inflammatory response syndrome (SIRS). The resulting metabolic stress is characterized by glycolysis, lipolysis, and proteolysis, which may escalate to an hypercatabolic response or "autocannabilism." Catabolic metabolism results in insufficiency of both specific and unspecific immunocompetent cells. CONCLUSIONS: Immunonutrition should be started early in such patients for an optimal beneficial effect, preferably via the enteral route. It should include medium chain and long chain triglycerides, polyunsaturated omega-3 and omega-6 fatty acids (in the ratio 1:2), olive oil, and conventional amino acid preparations supplemented with the conditionally essential amino acids arginine, glutamine, cysteine, and taurine.

[Nutrition in the surgical patient: immunonutrition]. / Nutrición en el paciente quirúrgico: inmunonutrición.

Malnutrition plays an important role in the rate of postoperative complications that interfere with our surgical activity, impairing immune response mechanisms; synthesis and regeneration processes are damaged and the fight against infection is altered. Preoperative and postoperative administration of diets enriched with diverse substances included under the name of "immunonutrients" reduces the rate of complications. Our knowledge about the mechanisms of action of each immunonutrient is increasing as well as the fact that the combined action of these substances improves the immune system and protects the organism against the negative effect of the systemic inflammatory response syndrome.

Single administration of thrombopoietin to lethally irradiated mice prevents infectious and thrombotic events leading to mortality.

A sufficiently high dose of thrombopoietin to overcome initial c-mpl-mediated clearance stimulates hematopoietic reconstitution following myelosuppressive treatment. We studied the efficacy of thrombopoietin on survival after supralethal total body irradiation (9 Gy) of C57BL6/J mice and the occurrence of infectious and thrombotic complications in comparison with a bone marrow graft or prophylactic antibiotic treatment. Administration of 0.3 microg thrombopoietin, 2 hours after irradiation, protected 62% of the mice as opposed to no survival in placebo controls. A graft with a supraoptimal number of syngeneic bone marrow cells (10(6) cells) fully prevented mortality, whereas antibiotic treatment was ineffective. Blood cell recovery was observed in the thrombopoietin-treated mice but not in the placebo or antibiotic-treated group. Bone marrow and spleen cellularity as well as colony-forming unit granulocyte-macrophage and burst-forming unit erythroid were considerably increased in thrombopoietin-treated mice relative to controls. Histologic examination at day 11 revealed numerous petechiae and vascular obstructions within the brain microvasculature of placebo-treated mice, which was correlated with hypercoagulation and hypofibrinolysis. Thrombopoietin treatment prevented coagulation/fibrinolysis disorder and vascular thrombosis. High fibrinogen levels were related to bacterial infections in 67% of placebo-treated mice and predicted mortality, whereas the majority of the thrombopoietin-treated mice did not show high fibrinogen levels and endotoxin was not detectable in plasma. We conclude that thrombopoietin administration prevents mortality in mice subjected to 9-Gy total body irradiation both by interfering in the cascade leading to thrombotic complications and by amelioration of neutrophil and platelet recovery and thus protects against infections and hemorrhages.

Secondary immunodeficiencies of horses.

FPT of immunoglobulin in foals is the commonest form of acquired immunodeficiency in horses. FPT predisposes foals to bacterial infections and septicemia and easily is preventable and treatable if breeding farms and veterinarians are attentive to optimum foaling management practices. Other forms of acquired immunodeficiencies are uncommon in horses, although immune function may be transiently suppressed by a wide variety of drugs, infections, or other conditions. As immunologic testing becomes more sophisticated and more readily available to equine practitioners, acquired immunodeficiencies are likely to be characterized more frequently in horses.

[The immunological effects of perftoran]. / Immunologichesie éffekty perftorana.

The effect of perftocarbonic emulsion-perftoran on the course of experimental lipopolysaccharide intoxication was studied in albino mice. Resistance of the animals to the endotoxin reduced 3 days after administration of 10 ml/kg of the preparation and increased 6 days after its administration. The effect of perftoran on the dynamics of some parameters of immunity and nonspecific resistance in CBA mice and guinea pigs was studied in immunodeficiency states induced by injection of 5-fluorouracil, cyclophosphamide, and irradiation. Activation of the phagocytic system occurred 3 days later, and activation of the parameters of cellular and humoral immunity 6 days later.

The significance of zinc for leukocyte biology.

Zinc is an essential element important for growth, the nervous system, and especially the immune system. Zinc deficiency as well as levels well above normal, due to high-dose treatment, showed an impaired immune function. This review summarizes the current status of zinc's significance for leukocyte biology and health. In detail, the physiology of zinc and the impaired immune functions in zinc deficiency syndromes are described. The regulation of innate immunity as well as the function and maturation of lymphocytes and monocytes is critically discussed as a system dependent on the zinc concentration in vivo and in vitro. Furthermore, the influence of zinc on experimental systems as well as on widely used immunostimulants is described, showing the importance of the knowledge of zinc concentration in in vitro leukocyte studies. The specific interactions of zinc with immunologically important serum proteins, signal transduction components, and membrane functions is summarized, showing the molecular basis of this interaction as known so far. Finally, the therapeutic use of zinc is critically discussed with new aspects also using the immunosuppressive effects of zinc. In conclusion, these data show that the zinc concentration should be taken into account whenever complex alterations of immune functions are observed.