Alternative Agents Research Articles

Alternative locust control with a dilutable linseed oil emulsion

AbstractLocust swarm control is still a main topic in agriculture and is often based on the extensive use of chemical agents that can be problematic for the environment and human health. Currently, only a few alternative control agents are available on the market, such as neem oil, the fungus Metarhizium sp., and the microsporidian Paranosema locustae. In this study, we improved the formulation of a botanical insecticide that is based on linseed oil and was found to be effective against the desert locust, Schistocerca gregaria. To make sure that linseed oil is most effective, we first tested several natural plant oils in a comparative laboratory study. Linseed oil performed best and resulted in 100% mortality within only 2 days after a single spray treatment. However, this linseed oil formulation contains three expensive essential oils, thus we further improved it to avoid costly essential oils. A much lower concentration of linseed oil was also found to be highly effective and killed adult S. gregaria within 3 days in an experiment performed under semifield conditions. Furthermore, a concentrated stock solution of this botanical insecticide was developed to increase stability and reduce shipping costs in areas where water for dilution is available. Mechanical treatment, applied during the preparation of this linseed oil emulsion, resulted in the formation of micro‐colloids, which prevent the separation of phases and enable 1:16 dilution with water containing bicarbonate. Interestingly, only 24 h after single spray treatment, locusts became immobile and most of them were unable to jump, which would make them easy prey for natural enemies. Later, insects died due to the hardening of the linseed oil emulsion. This novel linseed oil emulsion is harmless for humans, rather easy to produce, and remains stable over weeks in its concentrated form, which suggests that it is promising alternative agent for locust control.

Superior antibacterial properties of copper-doped titanium oxide films prepared by micro-arc oxidation

To prevent bacterial contamination and enhance wear-resistance of titanium-based tools and implants, it is crucial to develop functional coatings with inherent antimicrobial property and high surface hardness. In this study, the micro-arc oxidation technique was employed to prepare ceramic oxide films with antibacterial properties on titanium metal surfaces by incorporating trace amounts of copper. It was found that the phytic acid (C6H18O24P6) used as the chelating agent in the Cu-containing electrolyte can not be recycled and the adding of alternative chelating agent calcium gluconate (C12H22O14Ca) can significantly promote the cyclic utilization. The oxide film prepared by using C12H22O14Ca as the chelating agent exhibits a typical volcanic micro-arc oxidation morphology with uniform copper distribution, high hardness and excellent substrate adhesion. Most importantly, in vitro antibacterial tests demonstrate the outstanding antibacterial performance of Cu-doped TiO2 film with an antibacterial rate of up to 99.9% against Escherichia coli and Staphylococcus aureus.

In Vitro Anti-Inflammatory Activity and Structural Characteristics of Polysaccharides Extracted from Lobonema smithii Jellyfish.

Crude polysaccharides were extracted from the white jellyfish (Lobonema smithii) using water extraction and fractionated using ion-exchange chromatography to obtain three different fractions (JF1, JF2, and JF3). The chemical characteristics of four polysaccharides were investigated, along with their anti-inflammatory effect in LPS-stimulated RAW264.7 cells. All samples mainly consisted of neutral sugars with minor contents of proteins and sulphates in various proportions. Glucose, galactose, and mannose were the main constituents of the monosaccharides. The molecular weights of the crude polysaccharides and the JF1, JF2, and JF3 fractions were 865.0, 477.6, 524.1, and 293.0 kDa, respectively. All polysaccharides were able to decrease NO production, especially JF3, which showed inhibitory activity. JF3 effectively suppressed iNOS, COX-2, IL-1β, IL-6, and TNF-α expression, while IL-10 expression was induced. JF3 could inhibit phosphorylated ERK, JNK, p38, and NF-κB p65. Furthermore, flow cytometry showed the impact of JF3 on inhibiting CD11b and CD40 expression. These results suggest that JF3 could inhibit NF-κB and MAPK-related inflammatory pathways. The structural characterisation revealed that (1→3)-linked glucopyranosyl, (1→3,6)-linked galactopyranosyl, and (1→3,6)-linked glucopyranosyl residues comprised the main backbone of JF3. Therefore, L. smithii polysaccharides exhibit good anti-inflammatory activity and could thus be applied as an alternative therapeutic agent against inflammation.

Fumagillin inhibits growth of the enteric protozoan parasite Entamoeba histolytica by covalently binding to and selectively inhibiting methionine aminopeptidase 2.

Amebiasis is an important cause of morbidity and mortality worldwide, and caused by infection with the protozoan parasite Entamoeba histolytica. Metronidazole is currently the first-line drug despite adverse effects and concerns on the emergence of drug resistance. Fumagillin, a fungal metabolite from Aspergillus fumigatus, and its structurally related natural and synthetic compounds have been previously explored as potential anti-angiogenesis inhibitors for cancers, anti-microbial, and anti-obese compounds. Although fumagillin was used for human amebiasis in clinical trials in 1950s, the mode of action of fumagillin remains elusive until now. In this report, we showed that fumagillin covalently binds to methionine aminopeptidase 2 (MetAP2) and non-covalently but abundantly binds to patatin family phospholipase A (PLA). Susceptibility against fumagillin of the amebic strains in which expression of E. histolytica MetAP2 (EhMetAP2) gene was silenced increased compared to control strain. Conversely, overexpression of EhMetAP2 mutants that harbors amino acid substitutions responsible for resistance to ovalicin, a fumagillin analog, in human MetAP2, also resulted in decrease in fumagillin susceptibility. In contrast, neither gene silencing nor overexpression of E. histolytica PLA (EhPLA) affected fumagillin susceptibility. These data suggest that EhPLA is not essential and not the target of fumagillin for its amebicidal activity. Taken together, our data have demonstrated that EhMetAP2 is the primary target for amebicidal activity of fumagillin, and EhMetAP2 represents a rational explorable target for the development of alternative therapeutic agents against amebiasis.

Bacopa monnieri: A promising herbal approach for neurodegenerative disease treatment supported by in silico and in vitro research

Neurodegenerative disorders, caused by progressive neuron loss, are a global health issue. Among the various factors implicated in their pathogenesis, dysregulation of acetylcholinesterase activity has been recognized as a key contributor. Acetylcholinesterase breaks down the neurotransmitter acetylcholine, important for neural transmission. Evaluating phyto-compounds from Bacopa monnieri Linn. through in vitro and in silico analysis may expand their role as alternative therapeutic agents by modulating the function of acetylcholinesterase and complementing existing treatments. To accomplish this objective, chemical structures of phyto-compounds were retrieved from PubChem database and subjected to in silico and in vitro approaches. Virtual screening was performed through molecular docking and molecular dynamic simulation resulting in four top hit compounds including quercetin, apigenin, wogonin, and bacopaside X (novel lead compound for acetylcholinesterase inhibitor) with least binding score. Further, dose dependent acetylcholinesterase inhibition biochemical assay depicted that bacopaside X, apigenin, quercetin, and wogonin exhibited strong potential against acetylcholinesterase with IC50 values of 12.78 μM, 13.83 μM, 12.73 μM and 15.48 μM respectively, in comparison with the donepezil (IC50: 0.0204 μM). The in silico and in vitro research suggests that B. monnieri phyto-compounds have the potential to modulate molecular targets associated with neurodegenerative diseases and have a role in neuroprotection.

Effects of Seed of Different Mango Cultivars in Triton X-100 Induced Hyperlipdemic Rats

Hyperlipidemia is the most prevalent indicator for susceptibility to atherosclerotic heart diseases. The present study investigated the hypolipidemic potential of Mangifera haden, Mangifera pirie and combined extracts of Mangifera haden and Mangifera pirie seeds in Triton X-100 induced hyperlipidemic rats. Before the starting of the experiment, the animals were acclimatized to the laboratory conditions for a period of seven days. At the end of the acclimatization period, each rat was weighed and randomly divided into twelve groups of five animals each, comprising of test animals and control groups. Proximate analysis, toxicity studies, lipid profile parameters were determined in the study. The research study took place in the animal house of Biochemistry Department, University of Nigeria, Nsukka from July 2020 to August 2022. Proximate composition of Mangifera haden and Mangifera pirie seed extracts revealed that the (%) values of protein, lipid, crude fibre, ash, moisture, and carbohydrate are (4.82, 17.18, 4.29, 2.77, 8.39, 62.55) and (3.81, 20.20, 3.0, 1.0, 34.0, 37.99) respectively. Mangifera haden and Mangifera pirie were administered at different doses (200 mg, 300 mg, 500 mg) of the extracts per kilogram body weight of the animals while combined extract of Mangifera haden and Mangifera pirie were administered at 300 mg and 500 mg of the extract per kilogram body weight of the animals in Triton –Induced hyperlipidemic rats. Simvastatin and Atorvastatin were used as reference standards. Simvastatin was found to be an effective drug to Atorvastatin in lowering lipid profiles. The statistical analyses were carried out using one way ANOVA followed by Dunnett’s Post Hoc Multiple Comparisons test. Mangifera haden, Mangifera pirie and combined extracts of both species show significant decrease (P = 0.05) in the levels of serum Total Cholesterol, triacylglycerols, VLDL-C, LDL-C, Atherogenic index (A.I) and significant increase (P = 0.05) of serum HDL-C against Triton-Induced hyperlipidemic rats. The result also suggest that at 200 mg/kg Mangifera pirie and 300 mg/kg Mangifera haden body weight concentrations are an excellent lipid lowering agent. Single administration of either Mangifera haden or Mangifera pirie effectively suppressed the Triton-Induced hyperlipidemia in rats than the combined extracts. The organic extracts (Mangifera haden or Mangifera pirie) exhibited quite hypolipidemic potential when compared with one of the reference drugs, Atorvastatin which indicates that the organic extracts could be explored as an alternative therapeutic agent in the treatment of hyperlipidemia.

Preliminary Investigations on the Therapeutic Efficacy and Safety of Mixed Probiotic Lactic Acid Bacteria on Albino Rats Challenged with Shigella dysenteriae

This study investigates the potential of lactic acid bacteria (LAB) from the Nigerian beverage “kunun zaki” as alternative therapeutic agents against Shigella dysenteriae infections. In light of rising antibiotic resistance, the decline in probiotic usage prompted interest in LAB’s role in countering bacterial dysentery. Shigella dysenteriae, a significant cause of dysentery in developing nations, prompted this research which aims to carry out a preliminary investigation on the therapeutic efficacy and safety of mixed probiotic lactic acid bacteria on albino rats challenged with Shigella dysenteriae. Lactic acid bacteria, known for treating infections, were isolated from the beverage and tested against Shigella dysenteriae. The study employed 15 albino rats for in vivo trials, inducing diarrhea and treating with Lactococcus lactis and Lactobacillus brevis separately (T1 and T2) and combined in a 1 : 1 ratio (T3). Clinical parameters were observed before and after treatment. This revealed that L. lactis and L. brevis administration lowered rectal temperature from an average of 42°C caused by infection to 36.5°C. Stool consistency improved from light brown loose to dark brown semisolid, signifying reduced diarrhea. Bacteriological analysis displayed significant reduction ( p < 0.05 ) in Shigella counts in rat intestines across all treatments— 220 ± 2.88 C F U / g to 19.00 ± 1.77 C F U / g , 8.33 ± 0.88 C F U / g , and 65.00 ± 2.88 C F U / g for T1, T2, and T3, respectively. The mixed LAB treatment was notably effective. Lactic acid bacteria counts increased significantly in Shigella-treated rats versus the positive control. Hematology and liver function parameters showed no significant differences between treatments and untreated controls. Lactic acid bacteria from “kunun zaki” exhibited curative potential, individually or combined, against Shigella dysenteriae. These lactic acid bacteria also positively influenced gut microbiota in Shigella-infected albino rats.

Determination of Antimicrobial Properties of Raw and Commercial Honey against Methicillin Resistant Staphylococcus aureus

Background: In contrast to antibiotics, honey has strong antibacterial characteristics, a broad spectrum of action, no side effects, is non-toxic, and has no issues like building resistance. This study aimed to find out the antimicrobial properties of raw and commercial honey against Methicillin resistant Staphylococcus aureus and ATCC Staphylococcus aureus. 
 Methodology: Four different types of raw honey were collected from different flowers. Three different commercial honey samples were also collected from nearby grocery shops. Five Staphylococcus aureus samples were cultured in Mueller Hinton agar which was collected from the microbiology laboratory of BIHS General hospital. Then agar well diffusion method was carried out to determine the antimicrobial properties of raw and commercial honey.
 Results: The presence of antimicrobial activity is indicated by the absence of bacterial growth directly below the test sample. From this study we can see an inhibition zone around the honey well. The zone was not clear but from that we get to know that honey can prevent Methicillin resistant Staphylococcus aureus and the ATCC strain of it.
 Conclusion: The present investigation shows that bioactive constituents from raw and commercial honey have antimicrobial activity against Methicillin resistant Staphylococcus aureus and ATCC Staphylococcus aureus, however, this can be further explored as an alternative anti-staphylococcal agent.

A drug-delivery depot for epigenetic modulation and enhanced cancer immunotherapy

DNA methyltransferase inhibitors (DNMTis) have found widespread application in the management of cancer. Zebularine (Zeb), functioning as a demethylating agent, has exhibited notable advantages and enhanced therapeutic efficacy in the realm of tumour immunotherapy. Nevertheless, due to its lack of targeted functionality, standalone Zeb therapy necessitates the administration of a substantially higher dosage. In this investigation, we have devised an innovative nanodrug formulation, comprising the DNA methyltransferase inhibitor Zeb and pH-responsive chitosan (CS), hereinafter referred to as CS-Zeb nanoparticles (NPs). Our findings have unveiled that CS-Zeb NPs manifest heightened drug release within an acidic milieu (pH 5.5) in comparison to a neutral environment (pH 7.4). Furthermore, in vivo studies have conclusively affirmed that, in contrast to equivalent quantities of Zeb in isolation, the nanocomplex significantly curtailed tumour burden and protracted the survival duration of the B16F10 tumour-bearing murine model. Additionally, CS-Zeb NPs elicited an augmentation of CD8+ T cells within the peripheral circulation of mice and tumour-infiltrating lymphocytes (TILs). Notably, the dosage of CS-Zeb NPs was reduced by a remarkable 70-fold when juxtaposed with Zeb administered in isolation. To summarise, our study underscores the potential of CS-Zeb NPs as an alternative chemotherapeutic agent for cancer treatment.

Unraveling the mechanistic insights of sophorolipid-capped gold nanoparticle-induced cell death in Vibrio cholerae.

Cholera is one of the leading causes of mortality and morbidity worldwide. The treatment of cholera includes rehydration therapy, often combined with the administration of antibiotics (in severe cases). With the emergence and rapid spread of antimicrobial resistance, such microbial pathogens have become a compelling medical problem and a global threat. To combat the resistance to antibiotics, there is an urgent need for the discovery of novel and potent antimicrobial agents. The discovery of antimicrobial nanoparticles as an alternative to the existing antimicrobial regime has increased the hope for its use as one of the most promising tools against an array of microbial pathogens, including multidrug-resistant bacteria. Our recent report demonstrated that sophorolipid-capped gold nanoparticles (AuNPs-SL) exhibit potent antibacterial activity against Vibrio cholerae; however, the killing mechanism remained obscure. Metal nanoparticle-mediated killing of microbes occurs through non-specific mechanisms. To develop antimicrobial nanoparticles with better efficacy, knowledge of their specific mechanism of action is essential. In this work, we deduced the mechanistic insights of AuNPs-SL mediated cell death of V. cholerae. We observed that AuNPs-SL treatment evokes reactive oxygen species (ROS) formation. The surge in the ROS level triggers the overexpression of ROS-responsive genes, depolarization of the membrane, change in membrane permeability and leakage of intracellular proteins and DNA, depletion of ATP levels in the cell, DNA damage, and subsequent cell death. This study shows the possibility of use of AuNPs-SL as an alternative potential antimicrobial agent. IMPORTANCE Vibrio cholerae, a Gram-negative bacterium, is the causative agent of a fatal disease, "cholera." Prevention of cholera outbreak is possible by eliminating the bacteria from the environment. However, antimicrobial resistance developed in microorganisms has posed a threat and challenges to its treatment. Application of nanoparticles is a useful and effective option for the elimination of such microorganisms. Metal-based nanopaticles exhibit microbial toxicity through non-specific mechanisms. To prevent resistance development and increase antibacterial efficiency, rational designing of nanoparticles is required. Thus, knowledge on the exact mechanism of action of nanoparticles is highly essential. In this study, we explore the possible mechanisms of antibacterial activity of AuNPs-SL against V. cholerae. We show that the interaction of AuNPs-SL with V. cholerae enhances ROS production and membrane depolarization, change in permeability, and leakage of intracellular content. This action leads to the depletion of cellular ATP level, DNA damage, and subsequent cell death.

Study of a combined biological product with antibacterial and probiotic activity

Scientific relevance. The issue of antimicrobial resistance has acquired global significance, urging the search for and use of alternative antibacterial agents to treat infectious diseases. In particular, this situation prompts wider use of biotechnology-derived medicinal products based on bacteriophages and probiotics, including those of the metabolite type. The bacteriotropic (antimicrobial and probiotic) properties of pharmaceutical compositions based on bacteriophages and metabolites of probiotic bacteria suggest a qualitatively new combined antibacterial effect, as well as effectiveness against microorganisms resistant to antibiotics.Aim. The authors aimed to study the properties of a combined biological product with antibacterial and probiotic effects.Materials and methods. The study focused on a combined biological product consisting of a probiotic agent based on Lactobacillus exometabolites and a complex bacteriophage. The antimicrobial activity evaluation involved the Appelmans method, a disc diffusion method using lawn cultures homologous (Staphylococcus spp., Pseudomonas aeruginosa, Escherichia coli, Proteus spp., Enterococcus spp., Salmonella spp., and Shigella spp.) and non-homologous (Acinetobacter baumannii, Klebsiella pneumoniae, and Yersinia enterocolitica) to the complex bacteriophage, and a bioluminescence inhibition test using the genetically modified indicator strain E. coli lum+. The study used bacterial strains isolated from various clinical samples and biotopes in bacteriological laboratories of healthcare institutions in the Perm Territory in 2019–2022. The probiotic activity was assessed by the stimulating effect on model microorganisms of the normal flora.Results. The Appelmans method showed that the combined biological product had high antimicrobial activity against microorganisms homologous to the complex bacteriophage. The titres calculated for the combined biological product and its complex bacteriophage component were comparable and amounted to 10–6.6±0.01 and 10–6.9±0.01, respectively. The disc diffusion method demonstrated that the combined biological product had a more pronounced antibacterial effect on all tested strains than its individual components. The optical density values obtained with the combined biological product were 1.5 and 2 times higher than the values observed with control samples in Bifidobacterium bifidum 1 and Lactobacillus plantarum 8P-А3 cultures, respectively, which demonstrated the stimulating effect of the product on the normal flora. The study results suggest the compatibility of the phage and probiotic components of the combined biological product, as well as its high antimicrobial activity.Conclusions. The novel combined biological product has high specific and non-specific antimicrobial activity, which consists in the inhibition of pathogenic bacteria growth without affecting the normal flora. The combined biological product broadens the range of medicinal products having probiotic and antibacterial effects, particularly on microorganisms resistant to antibiotics.

THU468 Finding An Effective Treatment For Osteoporosis In Gaucher Disease

Abstract Disclosure: C. Lesniak: None. M.S. Akula: None. Background: Gaucher disease is a rare autosomal recessive disorder, leading to a deficiency of the enzyme glucocerebrosidase and accumulation of lipid-laden macrophages and dysfunction of multiple organs. The skeletal system is commonly affected resulting in reduced bone mineral density (BMD), marrow infiltration and bone infarction. Enzyme replacement therapy (ERT) has been a mainstay of treatment, and bisphosphonate therapy has been used to help treat osteoporosis, but newer agents are not well studied in this population. Case Description: The patient is a 62 year old female with a history of Gaucher disease Type 1 (GD1) and osteoporosis, treated with alendronate. She was diagnosed with GD1 in childhood and treated with glucocerebrosidase as ERT. She was diagnosed with osteoporosis in 2018 and started on bisphosphonates after a DXA scan showed a T-score at the lumbar spine of −3.2 and -1.4 at the left hip. She denied bone or back pain and has no history of any osteolytic lesions or osteonecrosis. Workup for secondary causes of osteoporosis was negative. She was taking alendronate 70 mg weekly, calcium 1800 mg daily, and vitamin D 4000 IU daily. Labs showed calcium 9.1 mg/dL, TSH 1.530 uIU/mL, PTH 34 pg/mL, and 25-hydroxy vitamin D 38.7 ng/mL. Repeat DXA scan showed worsening osteoporosis with a T-score at the lumbar spine of −3.4 and left hip of −2.5. As her BMD worsened while on alendronate for 3 years, teriparatide was offered as an alternative treatment. Discussion: Gaucher disease is a rare lysosomal storage disorder affecting multiple organs. Up to 90% of patients with GD1 have bone involvement of some kind. DXA scan should be done soon after diagnosis. Reduced BMD in GD1 is common and is associated with increased fracture risk. ERT has been the main management option to treat bone manifestations with improvement in BMD shown after 3-5 years. After 8 years of treatment with ERT, patients have been shown to reach the BMD of the age and sex matched population. In addition to ERT, calcium and vitamin D3 are recommended to increase BMD. There is no standard of treatment for osteoporosis in Gaucher patients, although bisphosphonates have been shown to improve BMD. Had our patient had early DXA scans, treatment may have been initiated sooner. A single case report showed improvement in BMD with the use of teriparatide after bisphosphonate failure. The efficacy of alternative agents, such as teriparatide and romosumab, in treating osteoporosis in patients with Gaucher disease needs to be further investigated. Presentation: Thursday, June 15, 2023

THU039 Use Of Desmopressin In The Differential Diagnosis Of Cushing’s Syndrome: Recent Experience At The NIH

Abstract Disclosure: R. McGlotten: None. L.K. Nieman: None. Background: Stimulation (stim) testing and petrosal sinus sampling (PSS) help determine the etiology of ACTH-dependent Cushing's syndrome (CS). As CRH is not available in the US, desmopressin (Desmo) is an alternative agent for both purposes. For the peripheral Desmo stim test, the reported sensitivity (ACTH:74 - 91%; cortisol (F): 81%) for Cushing's disease (CD) and specificity (ACTH:57-71%; F: 82%) for ectopic ACTH secretion (EAS) vary depending on the timepoints and criteria used for a response. The sensitivity of PSS was ∼ 95-99%. We evaluated our Desmo experience. Methods: We retrospectively reviewed 16 patients (pts) with pathologically-confirmed CS (and one with occult EAS) who underwent PSS (n=6) or Desmo stim testing (all) using a 10 ug IV dose at time 0 minutes (min). Stim test F and ACTH were measured -15, -1, 15, 30, 45, 60, 90, and 120 min. Percent response was calculated according to previous reports using the mean of -15 and 0 min and the mean of 15 and 30 min, or peak, ACTH values and the mean of 30 and 45 min, or peak, F levels. For PSS, ACTH was measured at -5, -1, 3, 5, and 10 min from left and right petrosal veins and a peripheral site. A pre- or post-stimulation gradient between peripheral and PS samples >2 and >3, respectively, was considered to indicate CD. Results: On stim test, positive cortisol responses >20% were found in 9/11 CD pts at 30/45min (range 29-175% vs -35 to 18%) and 10/11 with peak values (range 29 - 184% vs 17%). One of 4 EAS patients had a 30/45 min response (24% vs 6 - 18%) and 3 had a peak response (range 23-51% vs 7%). 9/11 CD patients had >35% ACTH response at 15/30 min (range 73 - 1175%, vs -13%, 7%), while 10/11 had a peak response (range 62 - 1736% vs 18%). However, 2/4 EAS patients had positive 15/30 min response (81%, 324% vs 1, 14%) and 3/4 had positive peak responses (range 44-324% vs 12%), decreasing specificity dramatically. An adrenal adenoma and occult EAS pt did not respond at all. Most CD peak responses were at 15 or 30 min (n=8), with others at 60 and 90 min. EAS peaks were at 0 - 90 min. 6 CD pts underwent PSS; all had a post stimulation PS:peripheral gradient >3 (range 9 - 831). In 4 EAS pts all gradients were <2 (range 1.2-1.4), although one had inadequate cannulation judged by prolactin. There was a good correlation between the 15 min PSS and the 10 min stim test values and type of response except for one CD pt who did not respond on the stim test but increased 362% at PSS. Discussion: Our small sample size showed a robust ACTH and F response to Desmo in nearly all CD but pts with EAS also respond, especially when peak values are used. Diagnostic accuracy was within the range of previous reports. EAS pts with stim test responses did not have a central:peripheral gradient during PSS, confirming an EAS tumor response to Desmo. Thus, negative stim test responses suggest EAS, while positive responses need confirmation by IPSS or other tests. The 120 min stim test values did not contribute to the diagnosis. Presentation: Thursday, June 15, 2023

Clostridioides difficile infection in the allogeneic hematopoietic cell transplant recipient.

Clostridioides difficile (CD) is one of the most important causes of diarrhea in hospitalized patients, in particular those who undergo an allogeneic hematopoietic cell transplant (allo-HCT) and who are more at risk of developing a CD infection (CDI) due to frequent hospitalizations, iatrogenic immunosuppression, and prolonged antibiotic cycles. CDI may represent a severe condition in allo-HCT patients, increasing the length of hospitalization, influencing the intestinal microbiome with a bidirectional association with graft-versus-host disease, and leading to unfavorable outcomes, including death. The diagnosis of CDI requires the exclusion of other probable causes of diarrhea in HCT patients and is based on highly sensitive and highly specific tests to distinguish colonization from infection. In adult patients, fidaxomicin is recommended as first-line, with oral vancomycin as an alternative agent. Bezlotoxumab may be used to reduce the risk of recurrence. In pediatric patients, vancomycin and metronidazole are still suggested as first-line therapy, but fidaxomicin will probably become standard in pediatrics in the near future. Because of insufficient safety data, fecal microbiota transplantation is not routinely recommended in HCT in spite of promising results for the management of recurrences in other populations.

Biomass-based Tanning Agent for Sustainable Leather Manufacture via Cyanuric Chloride Modified Chitooligosaccharide

Developing alternative tanning agents to avoid the potential environmental and human health risks from the conventional chrome tanning is essential for the leather industry. In this work, we prepared an eco-friendly biomass-based tanning agent dichlorotriazinyl chitooligosaccharide (DTCS) by modifying chitooligosaccharide (COS) with cyanuric chloride (CC) for chrome-free leather manufacture. The synthesis of such biomass-based tanning agent was systematically optimized to obtain the target product with high grafting degree of 67% and weight-average molecular weight (Mw) of 1465 g/mol. The non-pickling tanning procedure using DTCS was investigated, and the interactions between DTCS and collagen fibers were studied. Our results showed that the hydrothermal stability of the tanned leather was significantly increased, i.e., the shrinkage temperature (Ts) exceeding 82.0°C, and the mechanical properties were improved. Moreover, the organoleptic properties of leather (e.g., fullness, softness and grain tightness) exhibited obvious improvement. This research not only offers a reliable approach for cleaner leather manufacturing while addressing the underlying ecological pressure, but also highlights the emerging use of biomass materials in the leather industry.

Does the clopidogrel CYP2C19 genotype assay predict postprocedure stenosis in cerebral aneurysms treated with a flow diverter?

Flow diverters have emerged as a popular modality for treating cerebral aneurysms but require dual antiplatelet therapy (DAPT) after placement. Clopidogrel is a common choice but is a prodrug that some patients may not convert into an active metabolite. The CYP2C19 genotype assay is used to predict activation speed; however, limited data exist showcasing whether this genotype accurately predicts postprocedure complications after flow diversion treatment of cerebral aneurysms. Therefore, the authors sought to characterize whether CYP2C19 genotype correlated with the development of postprocedure intimal hyperplasia (stenosis) after flow diverter placement. Medical records were reviewed for patients who underwent flow diverter treatment of cerebral aneurysm at a single academic institution between January 1, 2012, and May 31, 2020. Patient demographics and comorbidities were reviewed alongside CYP2C19 genotype assay, DAPT regimen, and postprocedure angiogram data. Stenosis was defined based on review of angiogram data by two independent physicians. In this review of 120 unique cerebral aneurysms, 102 received DAPT with clopidogrel and 18 received DAPT with an alternative agent. Stenosis was present on 3-month follow-up angiogram for 35/102 (34.3%) aneurysms receiving DAPT with clopidogrel and in 11/18 (61.1%) aneurysms receiving an alternative DAPT regimen (p = 0.031). The CYP2C19 genotype did not correlate with postprocedure stenosis (p = 0.35). Clopidogrel was a significantly more effective DAPT agent for preventing stenosis when compared to nonclopidogrel DAPT regimens. The clopidogrel CYP2C19 genotype did not predict postprocedure stenosis in this cohort of 120 cerebral aneurysms treated with a flow diverter.

Penicillin Prophylaxis in Patients With Sickle Cell Disease Beyond Age 5 Years.

Patients with sickle cell disease (SCD) are at increased risk for invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae. Immunization and antimicrobial prophylaxis may prevent this complication, and landmark clinical trials support discontinuation of antimicrobial prophylaxis at age 5 years. However, antimicrobial prophylaxis continues in some patients indefinitely. The objective of this study was to evaluate the incidence of culture-positive IPD and other infections in the setting of penicillin prophylaxis in the pediatric SCD population. This was a single-center, retrospective cohort study of patients with SCD who continued antimicrobial prophylaxis with penicillin, compared with those whose antimicrobial prophylaxis was discontinued. Included patients were aged 5 to 18 years during the study period and had no history of IPD or surgical splenectomy. Patient charts were reviewed for demographics, immunizations, penicillin prescription history, and microbiologic culture data. Antimicrobial prophylaxis continued beyond age 5 years in 65% of patients, a higher percentage of whom had hemoglobin SS or S beta-zero disease. No patients whose antimicrobial prophylaxis was discontinued experienced IPD; 1 patient who continued antimicrobial prophylaxis died of S pneumoniae sepsis. Rates of other infections were comparable between groups (21% in prophylaxis versus 18% in no prophylaxis). These results support appropriate de-prescribing of antimicrobial prophylaxis in patients with SCD who are not at high risk for IPD. Further multicenter studies are needed to evaluate consequences of antimicrobial prophylaxis with alternative agents on antibiotic resistance, examine provider rationale for continuation of antimicrobial prophylaxis, and assess quality of life effects (e.g., medication adherence, adverse drug reactions) of antimicrobial prophylaxis.

Anti-tumour Activity of Bioactive Compounds Isolated from the Hemolymph and Mucus of the Garden Snail Helix aspersa against a Panel of Human Cancer Cell Lines

Cancer remains a significant global health concern, necessitating the search for new effective and safe anti-cancer agents. Natural products derived from plants and animals, including mollusks like snails, have gained attention as potential sources of novel anti-cancer compounds. Haemocyanins (Hcs), large copper-containing glycoproteins involved in oxygen transport in mollusks, have shown promise as anti-cancer agents. This study focuses on evaluating the in vitro anti-tumour efficacy of bioactive substances obtained from the hemolymph of the garden snail Helix aspersa on various human cancer cell lines representing different types of cancer. The results demonstrate that certain hemocyanin subunits from H. aspersa exhibit cytotoxic activity comparable to cisplatin, a widely used chemotherapy drug. Additional assays confirm the cytotoxic effects of the tested substances on cancer cells. The study underscores the potential of natural compounds from H. aspersa as alternative therapeutic agents for cancer treatment, while highlighting the need for further investigation. The identification of specific proteins responsible for the observed anti-proliferative effects in the mucus of H. aspersa provides insights for the development of novel cancer therapies.

Improving the post-harvest quality of fruits during storage through edible packaging based on guar gum and hydroxypropyl methylcellulose

Fruits are particularly susceptible to post-harvest decay. In this context, bio-based coatings could be a useful and sustainable approach to overcome this problem. The EU Commission is very restrictive about food additives and materials in contact with food, regulated respectively by Reg. UE (CE) 1333/2008 and Reg. UE (CE) 10/2011. In this research, different percentages of hydroxypropyl methylcellulose (H)-guar gum (G) (1–2% w/v) and potassium sorbate (PS) (0–2% w/v) were used to produce coatings to be applied on tomatoes (Solanum lycopersicum) and oranges (Citrus sinensis). The efficacy of the coatings was firstly evaluated through an accelerated test (28 °C 90% RH, 20 days) on artificially wounded fruits, and then under storage conditions (8 °C 95% RH, 6 weeks). The physical and chemical parameters of the fruits were periodically analyzed and used to evaluate the effect of the coatings on the fruit quality through a multivariate approach (PCA). All coatings were effective in preserving fruits under refrigeration against Penicillium spp. and Alternaria spp., but PS led to significant fruit weight loss despite its strong fungistatic activity. Biopolymers showed potential for preserving fruit freshness, but alternative antifungal agents without adverse weight effects should be explored using a similar statistical approach.

Erica arborea Bitkisi Kullanılarak Sentezlenen Çinko Nanopartiküllerin Biyoaktivitesinin Değerlendirilmesi

The synthesis of nanoparticles by environmentally friendly, cost-effective and simple methods has been the subject of much research in medicine and industry. In particular, it offers a promising approach for the development of next-generation nano-based drugs. This study synthesized zinc oxide nanoparticles (ZnO NPs) using Erica arborea (E. arborea) leaf extract as a stabilizing and reducing agent. The prepared ZnO NPs were characterized by UV-vis, FTIR and SEM-EDX analysis. SEM-EDX analysis showed that the nanoparticles were spherical in shape and showed strong signals of zinc metal. UV-vis analysis confirmed that the color of the solution changed to light yellow, indicating the formation of nanoparticles, and exhibited an absorption peak at 350 nm. FT-IR confirmed that the formation of nanoparticles was accompanied by metabolites of the leaf extract. The pharmacological potential of zinc nanoparticles synthesized by E. arborea was evaluated by antioxidant (DPPH method), antimicrobial (disk diffusion method) and lipid peroxidation (TBA method) activities. The biosynthesized ZnO NPs exhibited better antioxidant activity compared to the plant extract. The IC50 values of DPPH radical scavenging activity of ZnO NPs and leaf extract were 18.71±0.35 and 9.21±0.10, respectively. The lipid peroxidation inhibitory activity IC50 value of ZnO NPs was found to be 5.33±0.09. ZnO NPs were found to be sensitive against pathogenic bacteria P. aeruginosa, B. cereus, B. subtilis and S. aureus and fungal strain C. albicans. The findings suggest that synthesizing naturally synthesized zinc nanoparticles could be an alternative agent to physical and chemical methods. In addition, the pharmacological activity of nanoparticles will contribute to next-generation drug development studies.