Β-glucan Research Articles

Dose-response effect of prebiotic ingestion (\u03b2-glucans isolated from Saccharomyces cerevisiae) in diabetic rats with periodontal disease

BackgroundPeriodontal disease is one of the most frequent comorbidities in diabetic patients and can contribute to poor blood glucose control.ObjectiveTo evaluate the effects of ingesting different doses of beta-glucans (BG) isolated from Saccharomyces cerevisiae on alveolar bone loss (ABL) and inflammatory/metabolic parameters in normal and diabetic rats with ligature-induced periodontal disease (PD).DesignSixty male rats were assigned into two groups: non-diabetic or diabetic (i.p. 70 mg/kg streptozotocin) with PD. Then, groups were subdivided into five subgroups according BG doses: 0 mg/Kg; 10 mg/Kg; 20 mg/Kg; 40 mg/Kg or 80 mg/Kg. Animals received BG for 28 days and ligatures were placed on lower first molars during the last 14 days.ResultsABL of diabetic and non-diabetic animals receiving BG 40 mg/kg (1.33 ± 0.03 mm and 0.77 ± 0.07 mm, respectively) and 80 mg/kg (1.26 ± 0.07 mm and 0.78 ± 0.05 mm, respectively) doses was lower (p < 0.05) in comparison to respective controls (1.59 ± 0.11 mm and 0.90 mm ±0.08). COX-2 (Control: 1.66 ± 0.12; 40 mg/kg: 1.13 ± 0.07; 80 mg/kg: 0.92 ± 0.18) and RANKL expressions (Control: 1.74 ± 0.34; 40 mg/kg: 1.03 ± 0.29 ;80 mg/kg: 0.75 ± 0.21), together with the RANKL/OPG ratio (Control: 1.17 ± 0.08; 40 mg/kg: 0.67 ± 0.09; 80 mg/kg: 0.63 ± 0.28) were attenuated above the same dose (p < 0.05). BG did not influence (p > 0.05) metabolic parameters in non-diabetic rats. In diabetic animals, doses above 40 mg/kg reduced IL-1β (Control: 387 ± 66; 40 mg/kg: 309 ± 27; 80 mg/kg: 300 ± 14) and TNF-α (Control: 229 ± 19; 40 mg/kg: 128 ± 53; 80 mg/kg: 71 ± 25), blood glucose levels (Control: 402 ± 49; 40 mg/kg: 334 ± 32; 80 mg/kg: 287 ± 56), total cholesterol (Control: 124 ± 8; 40 mg/kg: 120 ± 10; 80 mg/kg: 108 ± 9), LDL-c + VLDL-c (Control: 106 ± 8; 40 mg/kg: 103 ± 10; 80 mg/kg: 87 ± 10) and triacylglycerols (Control: 508 ± 90; 40 mg/kg: 301 ± 40; 80 mg/kg: 208 ± 61), whereas increased HDL-c (Control: 18 ± 0.5; 40 mg/kg: 19 ± 1; 80 mg/kg: 21 ± 1) (p < 0.05). Optimal dose needed to reduce ABL was higher in diabetic animals with PD.ConclusionsBG ingestion reduced ABL and improved inflammatory profile in a dose-dependent manner. Best effects were achieved with doses above 40 mg/kg.

THE DILEMMA OF MILIARY COCCIDIODOMYCOSIS

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Coccidioidomycosis, a fungal infection endemic to the Southwest United States, can take on many appearances on chest imaging. A miliary pattern is seen less frequently. In the immunocompromised patient, this can be a quandary for physicians as it may mimic tuberculosis. CASE PRESENTATION: A 34-year-old woman with systemic lupus erythematosus, on immunosuppressive therapy, presented with two months of fevers, fatigue, and 25-pound weight loss. Additional symptoms included dry cough, pleuritic chest pain, and vision changes. Other history was notable for birthplace in a developing country and immigration to Arizona in early childhood. On presentation, a computed tomography of the chest revealed diffuse miliary nodules with confluent necrotizing pneumonia in the left lower lobe. Ophthalmology was consulted for her vision disturbances and found creamy chorioretinal lesions bilaterally on fundoscopic exam. Quantiferon testing was indeterminate. Beta-D glucan was elevated, as were coccidioidomycosis IgM and IgG antibodies. Bronchoscopy with bronchoalveolar lavage was subsequently performed, as the patient was unable to provide satisfactory sputum samples. These cultures were negative for tuberculosis, and the initiation of antitubercular therapy was avoided. Intravenous Amphotericin and oral Fluconazole was initiated during her hospitalization, followed by a prolonged course of Fluconazole at discharge. DISCUSSION: There was concern for disseminated tuberculosis, given the patient's miliary pattern on imaging, chorioretinitis, and history of birth place. As coccidioidomycosis is endemic to Arizona, the patient was empirically started on antifungal treatment, but precautions and workup of active tuberculosis were still taken. Antitubercular therapy was to be held until the appropriate respiratory samples were collected. The patient afforded this delay as she remained hemodynamically stable without oxygen requirements. This decision also minimized the risk of building resistance and subjecting the patient to potentially harmful side effects. Cultures resulted negative for tuberculosis, and the patient's rapid clinical improvement on antifungal therapy supported her diagnosis of pulmonary coccidioidomycosis. She was placed on oral fluconazole and prednisolone eye drops at discharge; her follow up with Infectious Diseases nine months later found the patient to be asymptomatic with near complete resolution of the nodules on chest imaging. CONCLUSIONS: Coccidioidomycosis can have acute to subacute presentations of pneumonia with imaging findings ranging from focal infiltrates and nodular opacities to cavitary lesions. A miliary pattern can also occur, which should prompt a thorough infectious history and consideration for more invasive testing prior to empiric treatment of tuberculosis in a stable patient. REFERENCE #1: Adam RD, Elliott SP, Taljanovic MS. The Spectrum and Presentation of Disseminated Coccidioidomycosis. The American Journal of Medicine. 2009;122(8):770-777. doi:10.1016/j.amjmed.2008.12.024 REFERENCE #2: Sotello D, Rivas M, Fuller A, Mahmood T, Orellana-Barrios M, Nugent K. Coccidioidomycosis with diffuse miliary pneumonia. Proc (Bayl Univ Med Cent). 2016 Jan;29(1):39-41. doi: 10.1080/08998280.2016.11929351. PMID: 26722164; PMCID: PMC4677849. DISCLOSURES: No relevant relationships by Nicholas Schlund, source=Web Response No relevant relationships by Aishan Shi, source=Web Response No relevant relationships by Ashley Thomas, source=Web Response

HERPES SIMPLEX VIRUS PNEUMONIA MASQUERADING AS DRUG-INDUCED PNEUMONITIS

TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: Drug induced pneumonitis is a major cause of adverse events during cancer therapy, and has become increasingly common with the use of immune-checkpoint inhibitor (ICI) therapy. Due to its rarity, ICI pneumonitis is a diagnosis of exclusion, and infection and malignancy must be ruled out. While multiple types of infection are typically assessed for, Herpes Simplex Virus (HSV) pneumonia is often not considered. We report the case of a 75 year old man with non-small cell lung cancer (NSCLC) on pembrolizumab who died despite aggressive treatment for a presumed ICI pneumonitis, and was found on autopsy to have had HSV pneumonia. CASE PRESENTATION: A 75 year old man with NSCLC presented to hospital with two days of dyspnea. The patient was being treated with a multi-drug chemotherapy regimen, including pembrolizumab. His last cycle was five days prior to admission. On admission, he was found to be hypoxic, saturating 70% on room air, with course bilateral crackles, and extensive bilateral ground glass opacities on chest CT. He did not have leukocytosis. Multiple infectious studies, including COVID-19, CMV, respiratory viral panel, legionella, mycoplasma, beta-D glucan, and galactomannan were negative. ICI pneumonitis was highest on the differential, and the patient was therefore started on solumedrol. After two days of no improvement, the solumedrol was increased and infliximab was added. The patient's respiratory status continued to worsen, and he was ultimately intubated. The patient underwent bronchoscopy once intubated, however, he expired before the studies resulted. Autopsy revealed a severe HSV pneumonia. DISCUSSION: ICI pneumonitis occurs in approximately 5% of patients treated with PD(L)-1 inhibitors, of which approximately 25% of cases are graded as severe or life-threatening. While the vast majority of patients with non-severe disease are successfully treated by withholding the ICI alone or in conjunction with glucocorticoids, those with more severe disease may require additional immunosuppression, and a small number of these patients die despite treatment. Due to its rarity, ICI pneumonitis is a diagnosis of exclusion, and diagnoses such as infection and malignancy should always be ruled out. The fact that its radiographic presentation is so heterogenous, with patterns as variable as those seen with COP, NSIP, HP, and AIP/ARDS, makes it all the more difficult to diagnose. HSV pneumonia is known to infrequently cause pneumonia in severely immunocompromised patients. A prospective observational study conducted in 2018 on immunocompromised adults with pneumonia not responding to empiric antibiotic therapy found it to be much more common than expected, with 42% of patients testing positive for HSV-1 on BAL, and 24% meeting criteria for HSV pneumonia. CONCLUSIONS: HSV pneumonia should be more frequently considered in immunocompromised patients suspected of having an ICI pneumonitis. REFERENCE #1: Nishino M, et al. Drug-related pneumonitis in the era of precision cancer therapy. JCO Precision Oncology. 2017 May 26; 1: 1-12. REFERENCE #2: Naidoo J, et al. Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy. J Clinical Oncology. 2017 Mar; 35 (7): 709-717. REFERENCE #3: Luzzati R, et al. Herpex simplex virus (HSV) pneumonia in the non-ventilated immunocompromised host: burden and predictors. J Infect. 2019 Feb; 78 (2): 127-133. DISCLOSURES: No relevant relationships by Jeffrey Ordner, source=Web Response No relevant relationships by Ariella Pratzer, source=Web Response No relevant relationships by Mark Sloane, source=Web Response No relevant relationships by Kristen Thomas, source=Web Response No relevant relationships by Karen Yang, source=Web Response

Beneficial effects of novel aureobasidium pullulans strains produced beta-1,3-1,6 glucans on interleukin-6 and D-dimer levels in COVID-19 patients; results of a randomized multiple-arm pilot clinical study.

ObjectiveIn this pilot clinical study, we report the beneficial effects of beta glucans derived from two strains AFO-202 and N-163 of a black yeast Aureobasidium pullulans on the biomarkers for cytokine storm and coagulopathy in COVID-19 patients.MethodsA total of 24 RT-PCR positive COVID-19 patients were recruited and randomly divided into three groups (Gr): Gr. 1 control (n = 8) – Standard treatment; Gr. 2: Standard treatment + AFO-202 beta glucan (n = 8); and Gr. 3, Standard treatment + combination of AFO-202 and N-163 beta glucans (n = 8) for 30 days.ResultsThere was no mortality or requirement of ventilation of the subjects in any of the groups. There was a decrease in D-Dimer values (751 ng/ml to 143.89 ng/ml) and IL-6 values (7.395–3.16 pg/ml) in Gr. 1 in 15 days but the levels increased to abnormal levels on day 30 (D-Dimer: 202.5 ng/ml; IL-6 55.37 pg/ml); which steadily decreased up to day 30 in groups 2 (D-dimer: 560.99 ng/dl to 79.615; IL-6: 26.18–3.41 pg/ml) and 3 (D-dimer: 1614 ng/dl to 164.25 ng/dl; IL-6: 6.25–0.5 pg/ml). The same trend was observed with ESR. LCR and LeCR increased while NLR decreased significantly in Gr. 3. CD4 + and CD8 + T cell count showed relatively higher increase in Gr.3. There was no difference in CRP within the groups.ConclusionAs these beta glucans are well known food supplements with a track record for safety, larger multi-centric clinical studies are recommended to validate their use as an adjunct in the management of COVID-19 and the ensuing long COVID-19 syndrome.

Evaluation of (1-3)-Beta-D glucan Assay for Diagnosis of Invasive Fungal Infections

Evaluation of (1-3)-Beta-D glucan Assay for Diagnosis of Invasive Fungal Infections

Hypoglycemic shock and acute liver injury in a dog associated with xylitol toxicity

An adult dog were evaluated for treatment loss of consciousness, convulsions, and severe tremors after ingestion of xylitol, a sugar alcohol used as a sweetener in various products. Clinical findings were noted as loss of consciousness, convulsions, and severe tremors, while physio-pathological findings included moderately to severely elevated serum activities of liver enzymes, hypoglycaemia and hypophosphatemia. To correct hypoglycaemia, dextrose was administered intravenously and to provide electrolyte homeostasis Izolen P was administered intravenously. Also, Milk Thistle (Silymarin) &amp;amp; Beta Glucan Complex, Hepatiale Forte Advanced (S-adenosylmethionine), Evicap (Vit E) and Asist (acetylcysteine) were used to correct acute liver damage. Values measured after the applied treatments showed that blood glucose levels and liver enzymes returned to normal, and the patient was discharged. Xylitol causes hypoglycaemia and acute liver damage in dogs after ingestion. As a growing number of products contain xylitol, clinicians should be aware that ingestion of xylitol could have life-threatening effects. This case report also carries the distinction of being the first xylitol toxicity reported in dogs in Turkey.

Oat and Barley in the Food Supply and Use of Beta Glucan Health Claims.

Beta glucan is a type of soluble dietary fibre found in oats and barley with known cholesterol-lowering benefits. Many countries globally have an approved beta glucan health claim related to lowering blood cholesterol, an important biomarker for cardiovascular disease. However, the use of these claims has not been examined. The aim of this study was to explore the range and variety of oat and barley products in the Australian and global market within a defined range of grain food and beverage categories and examine the frequency of beta glucan health claims. Australian data were collected via a recognised nutrition audit process from the four major Australian supermarkets in metropolitan Sydney (January 2018 and September 2020) and Mintel Global New Product Database was used for global markets where a claim is permitted. Categories included breakfast cereals, bread, savoury biscuits, grain-based muesli bars, flour, noodles/pasta and plant-based milk alternatives and information collected included ingredients lists and nutrition and health claims. Products from Australia (n = 2462) and globally (n = 44,894) were examined. In Australia, 37 products (1.5%) made use of the beta glucan claim (84% related to oat beta glucan and 16% related to barley beta glucan, specifically BARLEYmax®). Of products launched globally, 0.9% (n = 403) displayed beta glucan cholesterol-lowering claims. Despite the number of products potentially eligible to make beta glucan claims, their use in Australia and globally is limited. The value of dietary modification in cardiovascular disease treatment and disease progression deserves greater focus, and health claims are an opportunity to assist in communicating the role of food in the management of health and disease. Further assessment of consumer understanding of the available claims would be of value.

Current Knowledge of Medicinal Mushrooms Related to Anti-Oxidant Properties

Background: A renewed focus on medicinal mushrooms has brought forth a sustainable health dimension. Conventional health strategies are insufficiently integrated with sustainable health promotion. The health-promoting outcome of mushrooms has fascinated many groups during the past few years because of various primary and secondary metabolites in different cellular components. They contain many bioactive metabolites, including proteins (cytokines, ergothioneine), fibers, moisture, carbohydrates (uronic acid), folate, thiamine, ascorbic acid, vitamin D, calcium, potassium, polysaccharides (G. lucidum polysaccharides, alpha and beta glucans, and lentinan) polyketides, polyphenols (Protocatechuic acid, inonoblins A–vanillic acid, phelligridins D, E, and G, hydroxybenzoic acid, gallic acid, tannic acid, hispidine, gentisic acid, and tocopherol), nucleotides (adenosine, cordycepin), lovastatin, steroids, alkaloids, and sesquiterpenes. Objective: This study was conducted to gather information on the current knowledge of medicinal mushrooms, with respect to their antioxidant properties. Conclusions: The results indicated that mushrooms are a promising source of natural antioxidants. Of all mushrooms, the Ganoderma tsugae Murill exhibited an excellent antioxidant potential of 93.7–100% at 20 mg/mL.

Post-Prescription Audit Plus Beta-D-Glucan Assessment Decrease Echinocandin Use in People with Suspected Invasive Candidiasis.

Background and Objectives: Overtreatment with antifungal drugs is often observed. Antifungal stewardship (AFS) focuses on optimizing the treatment for invasive fungal diseases. The objective of the present study was to evaluate the utility of a post-prescription audit plus beta-D-glucan (BDG) assessment on reducing echinocandin use in persons with suspected invasive candidiasis. Materials and Methods: This is a prospective, pre-post quasi-experimental study of people starting echinocandins for suspected invasive candidiasis. The intervention of the study included review of each echinocandin prescription and discontinuation of treatment if a very low probability of fungal disease or a negative BDG value were found. Pre-intervention data were compared with the intervention phase. The primary outcome of the study was the duration of echinocandin therapy. Secondary outcomes were length of hospital stay and mortality. Results: Ninety-two echinocandin prescriptions were reviewed, 49 (53.3%) in the pre-intervention phase and 43 (46.7%) in the intervention phase. Discontinuation of antifungal therapy was possible in 21 of the 43 patients in the intervention phase (48.8%). The duration of echinocandin therapy was 7.4 (SD 4.7) in the pre-intervention phase, 4.1 days (SD 2.9) in persons undergoing the intervention, and 8.6 (SD 7.3) in persons in whom the intervention was not feasible (p at ANOVA = 0.016). Length of stay and mortality did not differ between pre-intervention and intervention phases. Conclusions: An intervention based on pre-prescription restriction and post-prescription audit when combined with BDG measurement is effective in optimizing antifungal therapy by significantly reducing excessive treatment duration.

Anxiolytic effects of administration of a commercially available prebiotic blend of galacto-oligosaccharides and beta glucans in Sprague-Dawley rats.

Prebiotics are nondigestible food agents that stimulate the growth of bacteria in the gut, whereas probiotics are live microorganisms that replace or restore beneficial bacteria in the digestive tract. Both agents have been shown to have beneficial qualities within the microbiota-gut-brain axis, but the behavioural effects of prebiotics have been less studied than probiotics. Whereas several studies have shown that prebiotics reduce inflammation and modulate anxiety in animals that are injected with lipopolysacccharides or chronically stressed animals, respectively, it is not yet known how they affect a healthy organism. Here, we tested the behavioural effects of galacto-oligosaccharides and beta glucan as a commercially available prebiotic blend in healthy, naïve Sprague-Dawley rats. We used the open field test and elevated plus maze to assess anxiety-like behaviour in controls and in rats that ingested the prebiotic blend in their drinking water. We also used the Morris Water Maze to assess spatial memory performance in controls and prebiotic treated rats. Rats treated with prebiotics spent more time in the intermediate zone of the open field test and in the open arms of the elevated plus maze, and exhibited a shorter latency to enter each of these zones. No significant differences between groups were found in the Morris Water Maze. Our results suggest that whereas prebiotics significantly reduced anxiety-like behaviours, it had no effect on spatial memory performance. Altogether, our data indicate that commercially available prebiotic beta glucan blends have anxiolytic effects in healthy rats.

Fomitopsis cajanderi extracts have differential tumoricidal actions on human MCF7 and U-937 cancer cells and inhibit TNF secretion by U-937 monocytes

Abstract This study aimed to determine if hot ethanol and aqueous extracts from the Fomitopsis cajanderi mushroom species are cytotoxic to human cancer cell lines and modulate TNF secretion by human monocytes. The hot ethanol extract was made via a 2 hour Soxhlet extraction of F. cajanderi fruiting body in ethanol using a cold finger condenser. The hot aqueous extract was made via a 2 hour decoction in water at 100°C. Human MCF7 mammary adenocarcinoma and U-937 histiocytic lymphoma cells were treated with increasing concentrations of extract or solvent controls and were assessed for cytotoxicity by XTT colorimetric assay. Effects of the aqueous extract on TNF secretion by PMA-differentiated, LPS-stimulated U-937 cells were determined by TNF ELISA. Glycosyl content and linkage analysis of the aqueous extract were assessed by the Complex Carbohydrate Research Center (Athens, Georgia, USA). The hot ethanol extract induced concentration-dependent cytotoxicity of MCF7 and U-937 cells, with stronger U-937 tumoricidal effects. The hot aqueous extract was not cytotoxic to MCF7 cells, but had cytotoxic effects on undifferentiated U-937 cells at high concentrations. The aqueous extract, found to contain beta glucans, inhibited TNF secretion by LPS-stimulated U-937 cells in a concentration-dependent manner. Hot ethanol and aqueous F. cajanderi extracts showed differential tumoricidal actions on human cancer cells. The ethanol extract was cytotoxic to the human cancer cells tested. The aqueous extract contained beta glucans reported to be immunomodulatory, and inhibited U-937 TNF secretion. These results warrant further research of F. cajanderi extracts as novel adjunctive anti-cancer and anti-inflammatory agents.

Diagnostic accuracy of the 1,3-beta-d-glucan test and lactate dehydrogenase for pneumocystis pneumonia in non-HIV patients

We evaluated the serum levels of (1–3)-beta-d-glucan (BG) and lactate dehydrogenase (LDH) as a tool to support pneumocystis pneumonia (PCP) diagnostic procedures in non-HIV patients. We retrospectively collected non-HIV (human immunodeficiency virus) patients presenting clinical features of PCP between April 1st, 2013, and December 31st, 2018. A total of 225 included patients were tested for Pneumocystis jirovecii by polymerase chain reaction (PCR) and methenamine silver staining. Based on different exclusion criteria, 179 cases were included in the BG group, and 196 cases were included in the LDH group. In each group, cases with positive immunofluorescence (IF) microscopy and PCR were considered proven PCP, while cases with only positive PCR were considered probable PCP. Fifty patients with negative IF and PCR results and proven to be non-PCP infection were chosen randomly as the control group. The cut-off levels of BG and LDH to distinguish non-PCP from probable PCP were 110 pg/mL and 296 U/L with 88% sensitivity and 86% specificity, and 66% sensitivity and 88% specificity, respectively. The cut-off levels of BG and LDH to distinguish non-PCP from proven PCP were 285.8 pg/mL and 379 U/L with 92% sensitivity and 96% specificity, and 85% sensitivity and 77% specificity, respectively. The cut-off levels of BG and LDH to distinguish non-PCP from proven/probable PCP were 144.1 pg/mL and 363 U/L with 90% sensitivity, 86% specificity and 80% sensitivity, 76% specificity respectively. BG and LDH are reliable indicators for detecting P. jirovecii infection in HIV-uninfected immunocompromised patients.

Nutrition and Immunity during Pandemic Viral Infection

Actual pandemic state of covid-19 infection leads to considerations of the quality of the state of immune system in population and to possible changes of this unfavorable state. In this review, the authors discuss the possibilities of nutritional changes, as the quality of nutrition in global sense is completely unsatisfactory. We assume that optimal supplementation with minerals and vitamins forms the basis for development of adequate immune responses not only to Covid-19 infection, but also to other bacterial and viral infections. It is necessary, however, to use optimal doses of supplements, as either too low or too high dose might decide between the use of a medicine or a poison. We conclude that the major responsibility for optimal approach to supplements lies not only with health professionals, but with the society. It is necessary to repeatedly offer quality information on neglected components influencing the health of the population, including stress, microbiome, adequate physical and psychical strain, and/or optimal diet. Beta glucans and their immunomodulatory activity helps not only in prevention of the whole spectrum of diseases connected with the immune system, but also in treatment of infectious diseases.

Establishment of a quantification method for β-glucans and their immune activity potential for quality control of β-glucan containing products

Beta glucans are complex glucose polymers well known for their immune modulatory properties. Therefore they are used and advertised in dietary supplements. Unfortunately there is no standardized test system for quality control of such health-related foods. This approach combined wet chemical and enzyme-based quantification methods (e.g. aniline blue, Glucatell®) with a cytokine secretion assay as parameter for immune activation to resolve this problem and to establish a quality control system for β-glucan containing products and extracts. Commercially available pure β-glucans with different origin and structure were used in this study. None of the methods allowed an accurate β-glucan quantification. Most promising was the test kit K-EBHLG (Megazyme). However, cytokine secretion from whole blood was detectable under the influence of β-glucans, but there was no correlation with the quantification results using the commercially available kits. Therefore, the quality control of β-glucan containing products needs further efforts.

Effects of starch synthase IIIa (&lt;i&gt;ssIIIa&lt;/i&gt;) genotype and grain hardness on the barley β-glucan content and grain morphology traits

オオムギの水溶性食物繊維β-グルカンが示す食後血糖値の上昇抑制などの健康機能性が注目されており，高β-グルカン品種の育成が求められている．本研究では，β-グルカン含有率の高いオオムギの育種において，簡易的な選抜技術の開発を目標として，これまでβ-グルカン含有率への強い関連性が示されている高アミロース性遺伝子amo1の極近傍にあるstarch synthase IIIa（ssIIIa）の遺伝子型とβ-グルカン含有率および穀粒形質との関係を解析した．解析には2組合せの交配に由来する後代系統群を用いた．「北陸皮54号」（後の「ゆきはな六条」）とamo1を有するもち性系統「四R系3755」との交配に由来するもち性の94の後代系統（F4–F5），「四R系3755」ともち性系統「はねうまもち」の交配に由来する165の後代系統（F4–F5）について，ssIIIa遺伝子型を識別するdCAPSマーカーで遺伝子型を判別し，β-グルカン含有率，SKCS穀粒硬度，硝子率，千粒重および空洞粒率を測定した．その結果，両組合せともssIIIa遺伝子型によってβ-グルカン含有率，SKCS穀粒硬度および硝子率に統計的有意差が認められ，「北陸皮54号」×「四R系3755」および「四R系3755」×「はねうまもち」の交配後代共に「四R系3755型」では「野生型」に比べ，β-グルカン含有率は約1.6倍多く，SKCS穀粒硬度は約23ポイント高く，硝子率は約7%高くなった．また，β-グルカン含有率はSKCS穀粒硬度と0.75から0.84の高い相関を示し，高β-グルカン化によって穀粒が硬くなる傾向が明らかとなった．これらのことから，amo1系統を母本とした高β-グルカン化を育種目標とする育種計画においては，ssIIIa遺伝子型やSKCS穀粒硬度を指標とした選抜が有効であると考えられた．

Enhancement of β-Glucan Biological Activity Using a Modified Acid-Base Extraction Method from Saccharomyces cerevisiae.

Beta glucan (β-glucan) has promising bioactive properties. Consequently, the use of β-glucan as a food additive is favored with the dual-purpose potential of increasing the fiber content of food products and enhancing their health properties. Our aim was to evaluate the biological activity of β-glucan (antimicrobial, antitoxic, immunostimulatory, and anticancer) extracted from Saccharomyces cerevisiae using a modified acid-base extraction method. The results demonstrated that a modified acid-base extraction method gives a higher biological efficacy of β-glucan than in the water extraction method. Using 0.5 mg dry weight of acid-base extracted β-glucan (AB extracted) not only succeeded in removing 100% of aflatoxins, but also had a promising antimicrobial activity against multidrug-resistant bacteria, fungi, and yeast, with minimum inhibitory concentrations (MIC) of 0.39 and 0.19 mg/mL in the case of resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, respectively. In addition, AB extract exhibited a positive immunomodulatory effect, mediated through the high induction of TNFα, IL-6, IFN-γ, and IL-2. Moreover, AB extract showed a greater anticancer effect against A549, MDA-MB-232, and HepG-2 cells compared to WI-38 cells, at high concentrations. By studying the cell death mechanism using flow-cytometry, AB extract was shown to induce apoptotic cell death at higher concentrations, as in the case of MDA-MB-231 and HePG-2 cells. In conclusion, the use of a modified AB for β-glucan from Saccharomyces cerevisiae exerted a promising antimicrobial, immunomodulatory efficacy, and anti-cancer potential. Future research should focus on evaluating β-glucan in various biological systems and elucidating the underlying mechanism of action.

The role of (1,3)-beta-D-glucan (BDG), as noninvasive technique for detection of invasive fungal infection (IFI)

Background: BDG is found in the cell walls of most fungi (eg, Candida, Aspergillus, Fusarium, Pneumocystis jirovecii). Serum BDG levels is high in the presence of a fungal infection. Its high serum levels may be detected before development of clinical symptoms and even prior to isolation or identification of the fungal organism via routine laboratory methods. Objectives: evaluate the performance of serum (1.3) beta -D glucan BDG in comparison with blood culture for diagnosis of the invasive fungal infections with Candida species. Methodology: The study was conducted on 50 patients divided in 3 group first group 20 patients with prolonged stay in ICU receiving broad spectrum antibacterial treatment, and second group 20 patients with diabetic foot and third group 10 patient healthy subjects with matched sex and age. All patients were subjected to full history taking, clinical examination and laboratory investigations Blood was examined with conventional methods (, Gram stain and culture on fungal media) and serum (1,3) beta -D-glucan was determined by ELISA. Result: The average serum concentration of BDG was higher in group II (121.25±88.9 pg/ml than group I (115.5±90.9 pg/ml),however there is no statistically significantly difference between group I and groupII, themean value of serum (1.3 beta D glucan) in patient with positive blood culture weresignificantly higher than those with negative blood culture there is significant relation between blood culture and the level of(1,3)beta D-glucan in serum. Blood culture could be considered as marker for detection of invasive fungal infection with sensitivity, specificity, PPV and NPV of, 46.43%, 100%, 100% and 11.76% respectively however (1.3) D glucan can detect invasive fungal infection with sensitivity, specificity, PPV and NPV of, 88.46%, 100%, 100% and 40%. Conclusion: Our results suggest that a positive (1,3)beta-D-glucan assay could be a superior test for diagnosis of candidemia in addition to the blood culture

Clinical Profile of Non-neutropenic Patients with Invasive Candidiasis: A Retrospective Study in a Tertiary Care Center.

Introduction: Invasive candidiasis (IC) is a major cause of morbidity and mortality in critically ill patients in the intensive care unit (ICU). In this study, we aim to analyze the clinical profile, species distribution, and susceptibility pattern of patients with IC.Methods: Case records of non-neutropenic patients ≥18 years of age with IC between January 2016 and June 2019 at a tertiary care referral hospital were analyzed. IC was defined as either candidemia or isolation of Candida species from a sterile site (such as CSF; ascitic, pleural, or pericardial fluid; or pus or tissue from an intraoperative sample) in a patient with clinical signs and symptoms of infection.Results: A total of 114 patients were analyzed, out of which 105 (92.1%) patients had bloodstream infection (BSI) due to Candida and 9 (7.9%) had IC identified from a sterile site. Central line-associated blood stream infection (27 patients, 23.6%) and a gastrointestinal source (30 patients, 26.3%) were the most common presumed sources for candidemia. The commonest species was Candida tropicalis 42 (36.8%), followed by Candida glabrata 20 (17.5%). Serum beta-D-glucan (BDG) was done only in 32 patients of the 114 (35.3%); among those who were tested, 5 (15.6%) had a BDG value of less than 80 pg/mL despite having Candida BSI. Fluconazole sensitivity was 69.5% overall. At 14 days after diagnosis of IC, 49.1% had recovered, with the remainder having an unfavorable outcome (32.4% had died and 18.4% had left against medical advice).Clinical significance: IC is a major concern in Indian ICUs, with a satisfactory outcome in only half of our patients. Serum BDG is a valuable test to diagnose blood culture-negative IC, but more studies are needed to determine its role in the exclusion of IC, as we had a small minority of patients with negative tests despite proven IC.Conclusion: We recommend sending two sets of blood cultures and serum BDG assay for all suspected patients. Initiating empiric antifungal therapy with an echinocandin is advisable, in view of increasing azole resistance and the emergence of Candida auris, with de-escalation to fluconazole for sensitive isolates after clinical stability and blood culture clearance.How to cite this article: Sridharan S, Gopalakrishnan R, Nambi PS, Kumar S, Sethuraman N, Ramasubramanian V. Indian J Crit Care Med 2021;25(3):267-272.

Beta-1,3 Oligoglucans Specifically Bind to Immune Receptor CD28 and May Enhance T Cell Activation.

Beta glucans are known to have immunomodulatory effects that mediated by a variety of mechanisms. In this article, we describe experiments and simulations suggesting that beta-1,3 glucans may promote activation of T cells by a previously unknown mechanism. First, we find that treatment of a T lymphoblast cell line with beta-1,3 oligoglucan significantly increases mRNA levels of T cell activation-associated cytokines, especially in the presence of the agonistic anti-CD3 antibody. This immunostimulatory activity was observed in the absence of dectin-1, a known receptor for beta-1,3 glucans. To clarify the molecular mechanism underlying this activity, we performed a series of molecular dynamics simulations and free-energy calculations to explore the interaction of beta-1,3 oligoglucans with potential immune receptors. While the simulations reveal little association between beta-1,3 oligoglucan and the immune receptor CD3, we find that beta-1,3 oligoglucans bind to CD28 near the region identified as the binding site for its natural ligands CD80 and CD86. Using a rigorous absolute binding free-energy technique, we calculate a dissociation constant in the low millimolar range for binding of 8-mer beta-1,3 oligoglucan to this site on CD28. The simulations show this binding to be specific, as no such association is computed for alpha-1,4 oligoglucan. This study suggests that beta-1,3 glucans bind to CD28 and may stimulate T cell activation collaboratively with T cell receptor activation, thereby stimulating immune function.

Hematological, immunological and histological changes in guinea pigs in the treatment of microsporia with drugs “Micromar” and “Biogluk”

Microsporia is a common infectious disease in the practice of a veterinarian. This disease carries a risk of human infection because it is anthropozoonotic. The main pathogen Microsporum sanis affects the upper layers of the skin and has the ability to stay on the body of an animal for up to two years. Therefore, treatment should be carried out by a complex method and be aimed at preventing the spread of the pathogen in the environment and increase the body's resistance in the fight against the disease. “Micromar” based on clotrimazole and povidone iodine and the immunostimulant “Biogluc” based on beta glucan and biotin were used to treat patients with microsporia. Clotrimazole and povidone iodine have antifungal and antiseptic properties, and beta glucan in combination with biotin stimulates the immune response and accelerates the regeneration of damaged skin. In order to determine the immune reactivity of the organism in the treatment of microsporia, hematological, immunological blood tests and histological examinations of the skin of guinea pigs infected with the pathogen M. canis were performed. The obtained results showed that when using the antifungal drug “Micromar” and immunostimulant “Biogluk” the number of leukocytes decreases from 11.13 ± 0.72 to 6.95 ± 0.10 109/L, rod-shaped neutrophils from 16.00 ± 1.29 to 6.17 ± 0.65 %, ESR from 5.67 ± 0.67 to 2.17 ± 0.31 mm/h, and the number of segmental neutrophils increases from 12.17 ± 1.47 to 22.00 ± 0, 86 %. There is a tendency to increase T-helpers. These changes indicate the development of an active immune response to the inflammatory process. In the structure of the skin there is a decrease in exudation and infiltration in the dermis, active trophism of hair follicles, which indicates the course of regenerative processes.