- Structural Stabilization of Human Transthyretin by Centella asiatica (L.) Urban Extract: Implications for TTR Amyloidosis. [Journal Article]
- BBiomolecules 2019 03 29; 9(4)
- Transthyretin is responsible for a series of highly progressive, degenerative, debilitating, and incurable protein misfolding disorders known as transthyretin (TTR) amyloidosis. Since dissociation of…
Transthyretin is responsible for a series of highly progressive, degenerative, debilitating, and incurable protein misfolding disorders known as transthyretin (TTR) amyloidosis. Since dissociation of the homotetrameric protein to its monomers is crucial in its amyloidogenesis, stabilizing the native tetramer from dissociating using small-molecule ligands has proven a viable therapeutic strategy. The objective of this study was to determine the potential role of the medicinal herb Centella asiatica on human transthyretin (huTTR) amyloidogenesis. Thus, we investigated the stability of huTTR with or without a hydrophilic fraction of C. asiatica (CAB) against acid/urea-mediated denaturation. We also determined the influence of CAB on huTTR fibrillation using transmission electron microscopy. The potential binding interactions between CAB and huTTR was ascertained by nitroblue tetrazolium redox-cycling and 8-anilino-1-naphthalene sulfonic acid displacement assays. Additionally, the chemical profile of CAB was determined by liquid chromatography quadruple time-of-flight mass spectrometry (HPLC-QTOF-MS). Our results strongly suggest that CAB bound to and preserved the quaternary structure of huTTR in vitro. CAB also prevented transthyretin fibrillation, although aggregate formation was unmitigated. These effects could be attributable to the presence of phenolics and terpenoids in CAB. Our findings suggest that C. asiatica contains pharmaceutically relevant bioactive compounds which could be exploited for therapeutic development against TTR amyloidosis.
- Oxidative stress, DNA damage, and mutagenicity induced by the extractable organic matter of airborne particulates on bacterial models. [Journal Article]
- RTRegul Toxicol Pharmacol 2019; 104:59-73
- The biological activity induced by the extractable organic matter (EOM) of size-segregated airborne Particulate Matter (PM) from two urban sites, urban traffic (UT) and urban background (UB), was ass…
The biological activity induced by the extractable organic matter (EOM) of size-segregated airborne Particulate Matter (PM) from two urban sites, urban traffic (UT) and urban background (UB), was assessed by using bacterial assays. The Gram-negative Escherichia coli (E. coli) coliform bacterium was used to measure the intracellular formation of Reactive Oxygen Species (ROS) by employing the Nitroblue tetrazolium (NBT) reduction assay and the lipid peroxidation by malondialdehyde (MDA) measurement. To the best of our knowledge, this is the first study using E. coli for assessing the bioactivity of ambient air in term of oxidative mechanism studies. E. coli BL21 cells were further used for DNA damage assessment by employing the reporter (β-galactosidase) gene expression assay. The bacterial strain S. typhimurium TA100 was used to assess the mutagenic potential of PM by employing the well-known mutation assay (Ames test). Four PM size fractions were assessed for bioactivity, specifically the quasi-ultrafine mode (<0.49 μm), the upper accumulation mode (0.49-0.97 μm), the upper fine mode (0.97-3 μm), and the coarse mode (>3.0 μm). The EOM of each PM sample included three organic fractions of successively increased polarity: the non-polar organic fraction (NPOF), the moderately polar organic fraction (MPOF), and the polar organic fraction (POF). The toxicological endpoints induced by each organic fraction were correlated with the concentrations of various organic chemical components determined in previous studies in an attempt to identify the chemical classes involved.
- Establishing a blood fructosamine reference range for the Brazilian population based on data from ELSA - Brasil. [Journal Article]
- PLPract Lab Med 2019; 13:e00111
- CONCLUSIONS: The reference intervals for fructosamine were affected by sex. Reference intervals stratified by sex would be more adequate in the interpretation of the fructosamine test.
- Approach to Molecular Diagnosis of Chronic Granulomatous Disease (CGD): an Experience from a Large Cohort of 90 Indian Patients. [Journal Article]
- JCJ Clin Immunol 2018; 38(8):898-916
- CONCLUSIONS: Substantial number of the patients lack NCF1 gene on both the alleles. This is often missed by advanced molecular techniques like Sanger sequencing and NGS due to the presence of pseudogenes and requires a simple Genescan method for confirmation. Thus, the diagnostic approach may depend on the prevalence of affected genes in respective population. This study identifies potential gene targets with the help of flow cytometric analysis of NADPH oxidase components to design an algorithm for diagnosis of CGD in India. In Indian population, the Genescan method should be preferred as the primary molecular test to rule out NCF1 gene mutations prior to Sanger sequencing and NGS.
- Administrations of autochthonous probiotics altered juvenile rainbow trout Oncorhynchus mykiss health status, growth performance and resistance to Lactococcus garvieae, an experimental infection. [Journal Article]
- FSFish Shellfish Immunol 2019; 86:269-279
- The present study was tested how Oncorhynchus mykiss can respond to dietary supplementations of autochthonous probiotics, including Lactobacillus delbrukei subsp. bulgaricus and Lactobacillus acidoph…
The present study was tested how Oncorhynchus mykiss can respond to dietary supplementations of autochthonous probiotics, including Lactobacillus delbrukei subsp. bulgaricus and Lactobacillus acidophilus and Citrobacter farmeri by measuring different parameters. To address that, 300 fish weighing 19.08-32.9 g were fed by probiotics-enriched diets, containing 5 × 107 CFU g-1 for 60 days. Our results indicated that probiotics, especially L. acidophilus and L. bulgaricus are involved in enhancing the growth performance of this species as compared with the control group. Blood profile (Hemoglobin and Hematocrit) showed significant (P < 0.05) increases in probiotic fed groups compared with the control. Serum lysozyme and complement activities were higher in probiotic-fed fish while similar changes were not observed in the case of bactericidal activity and Nitroblue Tetrazolium (NBT) reduction. Better colonization of lactic acid bacteria in fish intestine was observed following L. acidophilus and L. bulgaricus administrations (P < 0.001). Digestive enzyme activities of intestine, including amylase, trypsin, lipase and alkaline phosphatase were elevated either significant or insignificant while protease activity did not act the same. All probiotic treatments led to mild or strong (P < 0.001) up-regulation of cytokine and growth gene expressions of intestine in comparison with the control group. Higher in vitro antagonist activities of L. acidophilus and L. bulgaricus against the Lactococcus garvieae were coincident with in vivo challenge test. The relative percentage of survival (RPS) was obtained 63.71 and 51.56 for L. bulgaricus and L. acidophilus, respectively, which were higher in those treated fish as compared to control fish. Our results may suggest that the probiotics, applied here, can promote growth performance by improving digestive enzyme activity, gut micro flora and growth gene expression. Up-regulation of immune regulatory proteins may increase the non-specific immune responses and bacterial resistance in this species as well.
- Chronic granulomatous disease presenting with small bone osteomyelitis in a young child: A case report. [Case Reports]
- IJIndian J Pathol Microbiol 2018 Oct-Dec; 61(4):557-560
- Chronic granulomatous disease (CGD) is a life threatening inherited disorder with varied clinical presentations often characterized by recurrent bacterial and fungal infections along with widespread …
Chronic granulomatous disease (CGD) is a life threatening inherited disorder with varied clinical presentations often characterized by recurrent bacterial and fungal infections along with widespread granulomatous tissue response. The disease results from phagocytic defects characterized by deficiencies in oxidative burst of neutrophils. Nitroblue tetrazolium reduction test (NBT) and Dihydrorhodamine (DHR) with PMA stimulation by flow cytometry are quick, simple, sensitive and specific laboratory tests that help establish early and reliable diagnosis of CGD with an overall improvement in survival and disease prognosis. We report a case of 2-year old child who presented with small bone osteomyelitis involving bilateral feet and was later diagnosed to have autosomal recessive CGD due to mutation in NCF1 gene.
- Dietary L-Tryptophan potentiates non-specific immunity in Labeo rohita fingerlings reared under elevated temperature. [Journal Article]
- JTJ Therm Biol 2018; 74:55-62
- At present environmental scenario global climate change is a reality and its affect all living organism including fish. The aquatic ecosystem is the most affected system as it is the biggest sink for…
At present environmental scenario global climate change is a reality and its affect all living organism including fish. The aquatic ecosystem is the most affected system as it is the biggest sink for global warming and elevated temperature and obviously affects all the aquatic life forms. With this hypothesis an experiment was conducted to evaluate the effect of elevated temperature on Labeo rohita fingerlings and potential of dietary L-tryptophan (TRP) in mitigating the effects elevated temperature and enhancing the non-specific immunity. Seven hundred and twenty fishes were randomly distributed in three different thermal groups each with three replicates. The thermal groups were ambient temperature (26 °C), 34 and 38 °C. Then each thermal groups were fed with four different formulated diets containing 0. 0.36%, 0.72% and 1.44% TRP. The effect of dietary TRP supplementation was studied on stress responses, such as cortisol, blood glucose, histopathological changes in liver and kidney and immuno-hematological changes such as red blood cell count (RBC), haemoglobin (Hb), white blood cell count (WBC), lysozyme, nitroblue tetrazolium (NBT), total serum protein, albumin, globulin and albumin-globulin ratio. Subsequently the treated fish were subjected to challenge test with Aeromonas hydrophila. In the present study, primary stress markers were noticeably (p < 0.01) elevated with temperature stress and levels were reduced with nutritional supplementation of TRP. Similarly, immuno-hematological parameters were altered with the exposure of temeparture stress and got improved with dietary TRP supplementation. Results of the present study suggest that dietary supplementation of 1.44% tryptophan has definitive role in the mitigation of temperature stress and gives protection against bacterial infection to L. rohita.
- StatPearls: Immunodeficiency [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Immunodeficiency results from a failure or absence of elements of the immune system including lymphocytes, phagocytes and complement system. These immunodeficiencies can be either primary such as Bru…
Immunodeficiency results from a failure or absence of elements of the immune system including lymphocytes, phagocytes and complement system. These immunodeficiencies can be either primary such as Bruton’s disease or secondary as the one caused by HIV infection. Primary ImmunodeficiencyB-cell Deficiencies X- linked Agammaglobulinemia (Bruton’s disease): First described by Bruton. X-linked disorder. Found in male babies expressed around 5 to 6 months of age (maternal IgG disappears). In boys, pre-B cells did not differentiate into mature B lymphocytes. There is a mutation in the gene that encodes for a tyrosine kinase protein. Low level of all immunoglobulins (IgG, IgA, IgM, IgD and IgE) is present. Infants with X-linked agammaglobulinemia suffer from recurrent bacterial infections: otitis media, bronchitis, septicemia, pneumonia, and arthritis, and Giardia lamblia causes intestinal malabsorption. Intermittent injections of large amounts of IgG keep the patient alive, but a patient may die at a younger age if infection with antibiotic-resistant bacteria occurs. Bone marrow transplantation is critical. Selective Immunoglobulin IgA Deficiencies : IgA deficiency is more common than other deficiencies of immunoglobulins.. These patients are more prone to recurrent sinus and lung infections. A malfunctioning in heavy-chain gene switching may cause this problem. Treatment should not include gammaglobulin preparations to prevent hypersensitivity reactions. T-cell Immunodeficiencies Congenital thymic Aplasia (DiGeorge Syndrome): Tetany is present. Fungal and viral infections are common. A transplant of the fetal thymus is needed to correct this deficiency. Chronic Mucocutaneous Candidasis: Selective defect in functioning of T-cells. Patient with this disorder usually have a normal T-cell mediated immunity to microorganisms other than Candida. B-cells function is normal. Disorders affect both genders, and it is inherited. Patient in addition to the above will have other disorders like parathyroid deficiencies. Antifungals are useful. Hyper-IgM syndrome: This disorder is characterized by bacterial infections including pneumonia, meningitis, otitis, among others that start in early childhood. High levels of IgM. Other immunoglobulins are defective. Lymphocytes are normal in numbers. The gene encoding the CD40 ligand on T lymphocytes is faulty. B and T lymphocyte cooperation in the immune response is compromised. The failure to interact with CD40 results in an inability of the B cell to switch from the production of IgM to the other classes of antibodies. Immunoglobulin therapy is recommended. Interleukin-12 receptor deficiency: Mycobacterial infections are frequent due to the lack of the interleukin-12 receptor. Treatment involves selective antimicrobials. T-cell and B-cell Deficiencies Severe combined immunodeficiency disease (SCID): There is a failure of early stem cells to differentiate into T and B lymphocytes. Deficiency of the interleukin-2 receptor is the most prevalent. Other problems are due to defective genes encoding ZAP-70, Janus kinase 3 and the genes involved in the DNA recombination of immune cells receptors: RAG1 and RAG2. Clinically characterized by a variety of infections, including those caused by opportunistic pathogens. Selective antibiotics, antivirals, and antifungals are available after the pathogen identification. Immunosuppressive therapy is not needed after allograft transplantation. Wiskott-Aldrich syndrome: This syndrome is associated with normal T-cell numbers with reduced functions, which get progressively worse. IgM concentrations are reduced, but IgG levels are normal. Both IgA and IgE levels are elevated. These patients have a defective WASP which is involved in actin filament assembly. Immunodeficiency with ataxia-telangiectasia: This is a deficiency of T-cells associated with a lack of coordination of movement (ataxia) and dilation of small blood vessels of the facial area (telangiectasis). T-cells and their functions are diminished to various degrees. B-cell numbers and IgM concentrations are normal to low. IgG is often reduced, and IgA is considerably reduced. There is a high incidence of malignancy, especially leukemias, in these patients. MHC deficiency (Bare leukocyte syndrome): This subjects have have fewer CD4+ or CD8+ T lymphocytes that predispose to these individuals to be prone to recurrent infections. Antibody production is affected and predispose to bacteremia. Complement Deficiencies Hereditary angioedema : This disease has an autosomal dominant genetic pattern. Caused by C1 inhibitor deficiency. Clinically characterized by generalized edema including the one leading to acute suffocation. Therapy with oxymetholone and danazol can be helpful in correcting the defect. Recurrent infections: Frequent infections by extracellular bacteria may be caused by C3 deficiency. C5 deficiency predisposes to viral infections. Patients with deficiency of the membrane attack complex (MAC) are particularly susceptible to bacteremia caused by Neisseria species. Autoimmune diseases This are caused by C2 and C4 deficiencies and mimic systemic lupus erythematosus. Phagocyte Deficiencies Chronic granulomatous disease (CGD): It is mostly an X-linked disorder. It is clinically characterized by a defective NADPH that interferes with the intracellular ability of neutrophils to kill engulfed bacteria species. NAPDH oxidase is required for the generation of peroxidase and superoxides that will kill the organisms. The intracellular survival of the organisms leads to the formation of a granuloma, an organized structure consisting of mononuclear cells. These granulomas can become large enough to obstruct the stomach, esophagus, or bladder. Patients with this disease are very susceptible to opportunistic infection by certain bacteria and fungi especially with Serratia and Burkholderia. Nitroblue tetrazolium (NBT) dye reduction test confirms the diagnosis of CGD and the dichlorofluorescein (DCF) test is also useful. Aggressive therapy with wide spectrum antibiotics and antifungal agents is required. Leukocyte adhesion deficiency syndrome: Characterized by pyogenic infections including pneumonia and otitis. It is an autosomal recessive disease, and the faulty gene encodes for an integrin. There is an impaired adhesion and defective phagocytosis of bacteria. Treatment involves the use of selective antibiotics. Secondary Immunodeficiency Use of Drugs (Steroids) : Administration of steroids has direct effects on immune cell traffic and functions. T cells are more affected than B cells. Cytokine synthesis is inhibited. Nutrient Deficiencies : They are associated with impaired immune system. Affects cell-mediated immunity, antibody production, phagocyte function, complement system and cytokine synthesis. Aggravated by infections. Multiple enzymes with important roles require zinc, iron and other micronutrients. Obesity : It may cause impaired immune responses. There is altered NK function. Cytotoxicity is compromised and the ability of phagocytes to kill microorganisms. Acquired Immune Deficiency Syndrome (AIDS) : Caused by human immunodeficiency virus (HIV), which is a retrovirus transmitted sexually, perinatally or blood products. Immune dysfunction results from the direct effects of HIV and impairment of CD4 T cells. HIV proteins may act as superantigens. There is decreased responses to antigens and mitogens. Interleukin-2 and other cytokines are decreased. Infected cells may be killed by HIV-1 specific CD8+ T cells. In HIV-1 infection neutralizing antibodies appear to be ineffective in controlling viral replication and infection.
- Evaluation of immunotropic activity of gold nanocolloid in chickens. [Journal Article]
- JTJ Trace Elem Med Biol 2018; 47:98-103
- Gold nanoparticles (AuNPs) are one of the most examined nanomaterials, but information about their immunogenic potential is still insufficient. Understanding interaction of AuNPs with immune system i…
Gold nanoparticles (AuNPs) are one of the most examined nanomaterials, but information about their immunogenic potential is still insufficient. Understanding interaction of AuNPs with immune system is essential in designing their safety and possibilities of biomedical applications. An experiment was conducted to determine immunotropic activity of gold nanocolloid (AuNPs) administered orally to chickens depending on dose and duration time. 162 birds were assigned to 9 experimental groups of 18 birds each. The control group (C) did not receive AuNPs. Groups: T10.5, T11.0, T11.5, T12.0, received nano-gold in a rate of 0.5 mg/kg body weight/d, 1.0 mg/kg body weight/d, 1.5 mg/kg body weight/d and 2.0 mg/kg body weight/d in 8-14, 22-28 and 36-42 days of the life. The birds in groups T20.5, T21.0, T21.5, T22.0, received nano-gold in the same doses, but only in 8-10, 22-24 and 36-38 days of life. Phagocytic activity of leukocytes was determined in vitro using Staphylococcus aureus 209P strain, their respiratory burst activity was quantified by nitroblue tetrazolium reduction test. Serum lysozyme content was determined by the turbidimetric method. The Wintrobe method was used to determine the erythrocyte sedimentation rate. Ceruloplasmin in the blood plasma was estimated by the p-phenylenediamine colorimetric method. The level of chicken immunoglobulins: IgA, IgM and IgY and interleukin IL-6 in the blood were determined using ELISA tests. The lowest dose of AuNPs, independently on duration time had no effect on immune parameters of chickens. In all other groups receiving nano-gold for a shorter period (T2), there was an increase in the respiratory burst activity of leukocytes and a drop in lysozyme activity in blood. The higher doses (1.5 and 2.0 mg/kg body weight/d) of the nano-gold administered for the longer time period had a pro-inflammatory effect, as indicated by an increase in the level of interleukin 6 and ceruloplasmin activity as well as the erythrocyte sedimentation rate. They also contributed to an elevation of class IgA and IgY contents in blood. The results of the study revealed that the influence of nano-gold on immune response of chickens were dependent both on dose and duration time. Long lasting administration of higher doses of AuNPs contributed to adverse effect in form of inflammation response. To avoid the development of inflammatory reaction, administered dose of nano-gold should not exceed 1.0 mg/kg body weight/d.
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- Neutrophil bactericidal activity through the stages of placement of different dental implants depending on their chemical composition. [Journal Article]
- WLWiad Lek 2017; 70(5):921-924
- CONCLUSIONS: The placement of dental implants systems led to an increase in the share of active neutrophils in the peripheral blood of the patients in 5-7 days following the procedure of implant insertion. However, this indicator for implant systems with a higher content of Ti in the remote period returned to its original value, which indicates their higher biocompatibility with the tissues of the human body.