Prophylactic Drugs Research Articles

A Survey of the Prevalence of Infections Present among Inpatients in a Tertiary Care Hospital in 2023

Objective: To explore the current infection rate among inpatients in a tertiary hospital in 2023, to understand the infection situation in the hospital, and to provide a reliable basis for carrying out further hospital infection prevention and control and other work. Methods: Inpatients of a tertiary hospital on a certain date in 2023 were selected, and the survey data were extracted with the Apricot Grove real-time monitoring system using a combination of questionnaires and medical record data. Results: The infection rate was 12.63%, of which the hospital infection rate was 2.25% and the community infection rate was 10.38%. Lower respiratory tract infections accounted for 77.28% of the community infections, and lower respiratory tract infections accounted for 73.44% of the cases of hospital infections, with a total of 44 strains of pathogens isolated from hospital infections, and a total of 218 strains of pathogens isolated from community infections. The total application rate of antimicrobial drugs was 31.67%, the proportion of prophylactic drugs in the whole hospital was 9.66%, the proportion of therapeutic drugs was 90.33%, and the rate of bacterial culture delivery was 39.18%. Conclusion: The infection rate survey truly reflects the dynamics of infection in this hospital, makes clearer the key departments and key links of hospital infection prevention and control, further provides the basis for targeted infection control, and improves the knowledge and execution of hospital infection prevention and control by medical staff.

Could prophylactic antivirals reduce dengue incidence in a high-prevalence endemic area?

Prophylactic drugs against dengue are currently under development. In this study, we explored how such prophylactic approaches might affect dengue cases in four communes of Nha Trang City, Vietnam. A community level dengue transmission survey indicated high levels of previous exposure to dengue (89.7%; 95% CI: 87.2,92.0). We fitted a spatially explicit model to an observed outbreak and simulated likely effectiveness of Case-Area Targeted Interventions (CATI) and One-Time Mass Distribution (OTMD) of drug and vector control strategies. Increasing radius and effectiveness and decreasing delay of CATI was most effective, with drugs being more effective in averting dengue cases than vector control. Using an OTMD approach early in the outbreak required the least number of treatments to avert a case, suggesting that OTMD strategies should be considered as pre-emptive rather than reactive strategies. These findings show that pre-emptive interventions can substantially reduce the burden of dengue outbreaks in endemic settings.

Attenuation of Nerve Agent Induced Neurodegenerative and Neuroinflammatory Changes in Rats with New Combination Treatment of Galantamine, Atropine and Midazolam.

Acute nerve agent exposure can kill a person within minutes or produce multiple neurotoxic effects and subsequent brain damage with potential long-term adverse outcomes. Recent abuse of nerve-agents on Syrian civilians, during Japan terrorist attacks, and personal assassinations in the UK, and Malaysia indicate their potential threat to world population. Existing nerve agent antidotes offer only incomplete protection especially, if the treatment is delayed. To develop the effective drugs, it is advantageous to elucidate the underlying mechanisms of nerve agent-induced multiple neurological impairments. This study aimed to investigate the molecular basis of neuroinflammation during nerve agent toxicity with focus on inflammasome-associated proteins and neurodegeneration. In rats, NOD-like receptor family pyrin domain containing 3 (NLRP3), and glial fibrillary acidic protein (GFAP) immunoreactivity levels were considerably increased in the hippocampus, piriform cortex, and amygdala areas after single subcutaneous soman exposure (90µg/kg-1). Western analysis indicated a notable increase in the neuroinflammatory indicator proteins, high mobility group box 1 (HMGB1) and inducible nitric oxide synthase (iNOS) levels. The presence of fluorojade-C-stained degenerating neurons in distinct rat brain areas is indicating the neurodegeneration during nerve agent toxicity. Pre-treatment with galantamine (3mg/kg, - 30min) followed by post-treatment of atropine (10mg/kg, i.m.) and midazolam (5mg/kg, i.m.), has completely protected animals from death induced by supra-lethal dose of soman (2XLD50) and reduced the neuroinflammatory and neurodegenerative changes. Results highlight that this new prophylactic and therapeutic drug combination might be an effective treatment option for soldiers deployed in conflict areas and first responders dealing with accidental/deliberate release of nerve agents.

Role of nonsteroidal anti-inflammatory drugs on change in macular volume postcataract surgery in diabetic eyes: A retrospective comparative study.

Diabetic eyes suffer from variety of complications including macular edema. Cataract surgery is the most commonly done procedure throughout the world and majority would be diabetics. As pseudophakic-cystoid macular edema (CME) is a known complication following cataract surgery, our study concentrated on finding the role of prophylactic topical nonsteroidal anti-inflammatory drugs (NSAIDs) on change in total macular volume (TMV) postcataract surgery in diabetic eyes. To evaluate the role of NSAIDs on change in TMV postcataract surgery in diabetic eyes. Retrospective comparative study. Data were collected from the medical records department of our institute constituting diabetics undergoing cataract surgery from June-2021 to February-2022. Eighty diabetic eyes were divided into two groups: one group were given topical nepafenac drops and another who were not given. Demographic details, diabetic retinopathy stage, preoperative optical coherence tomography (OCT), and postoperative day (POD) 7, day 28, and 3 months OCT were collected. Statistical analysis was done to compare the change in TMV between both the groups. Student's t-test and Chi-squared/Fisher's exact test were employed to find statistically significant differences between the two groups using SPSS-22.0 software. In our study, the mean age in the group with nepafenac was 60.93 ± 5.86 years and 31 (77.5%) had moderate nonproliferative diabetic retinopathy (NPDR), and in the group without nepafenac, the mean age was 58.53 ± 7.41 years and 30 (75%) had moderate NPDR. Majority of the individuals in the study group were known diabetic for 2-5 years. Change in TMV at POD 3 months among two groups was not statistically significant; P = 0.758 (P < 0.05-significant). Our study concluded that topical-NSAIDs played no role in postoperative period following cataract surgery with respect to change in TMV in diabetic eyes. Thus, prophylactic usage of topical-NSAIDs can be a burden on patient as it has no role in prevention of pseudophakic-CME in those with the duration of diabetes mellitus <5 years and with mild-to-moderate NPDR.

Doxycycline, levofloxacin, and moxifloxacin are superior to ciprofloxacin in treating anthrax meningitis in rabbits and NHP.

Efficient treatment of anthrax-related meningitis in patients poses a significant therapeutic challenge. Previously, we demonstrated in our anthrax meningitis rabbit model that ciprofloxacin treatment is ineffective with most of the treated animals succumbing to the infection. Herein we tested the efficacy of doxycycline in our rabbit model and found it highly effective. Since all of our findings are based on a rabbit model, we test the efficacy of ciprofloxacin or doxycycline in a specific central nervous system (CNS) model developed in non-human primates (NHPs). Similar to rabbits, ciprofloxacin treatment was ineffective, while doxycycline protected the infected rhesus macaques (n = 2) from the lethal CNS Bacillus anthracis infection. To test whether the low efficacy of Ciprofloxacin is an example of low efficacy of all fluoroquinolones or only this substance, we treated rabbits that were inoculated intracisterna magna (ICM) with levofloxacin or moxifloxacin. We found that in contrast to ciprofloxacin, levofloxacin and moxifloxacin were highly efficacious in treating lethal anthrax-related meningitis in rabbits and NHP (levofloxacin). We demonstrated (in naïve rabbits) that this difference probably results from variances in blood-brain-barrier penetration of the different fluoroquinolones. The combined treatment of doxycycline and any one of the tested fluoroquinolones was highly effective in the rabbit CNS infection model. The combined treatment of doxycycline and levofloxacin was effective in an inhalation rabbit model, as good as the doxycycline mono-therapy. These findings imply that while ciprofloxacin is highly effective as a post-exposure prophylactic drug, using this drug to treat symptomatic patients should be reconsidered.

Effects of open-label sesame oil applied to cardiac surgery patients in preventing amiodarone-induced phlebitis: A randomized controlled trial.

Amiodarone is a prophylactic rhythm-regulating drug used to prevent arrhythmia; However, especially during infusion, it has the potential to cause a number of complications, especially phlebitis. The aim of the study is to determine the effects of sesame oil, which has the potential to prevent phlebitis that may occur during amiodarone infusion administered to patients after cardiac surgery. This prospective, two-arm (1:1), block randomized controlled interventional study. This study was conducted with 44 patients treated in the coronary intensive care unit of a university hospital, who received parenteral infusion of amiodarone. Sesame oil was applied superficially by applying 10 drops to a 10 cm perimeter of the cannula for 10 min. This application was repeated every 8 h during the 24-h amiodarone infusion. No intervention was made to the patients in the control group. However, standard nursing care measures and a standard transparent dressing were applied to the patients in both groups during the peripheral catheter application phase. Patients in the intervention and control groups were evaluated in terms of phlebitis at the end of every 24 h using the Visual Infusion Phlebitis Scale. The study was reported according to the CONSORT declaration. Phlebitis symptoms occurred in 15/22 (68.2%) of the patients in the intervention group on the first day, 3/22 (13.6%) on the second day and 2/22 (9.1%) of the patients on the third day, while in the control group, 20/22 (90.9%) of the patients had phlebitis on the first day and 2/22 (9.1%) on the second day. The incidence of phlebitis was 20/22 (90.9%) in the intervention group and 22/22 (100%) in the control group. There was no statistically significant difference in phlebitis symptoms between groups. The research results showed that the application of sesame oil did not significantly reduce the frequency of phlebitis. However, a trend indicating delayed onset of phlebitis symptoms was observed in the sesame oil group. Nevertheless, larger sample studies are needed. These studies are expected to assist in determining the effects of sesame oil on phlebitis more precisely and provide stronger support for the results. Training of nurses on non-pharmacological methods should be supported and opportunities should be given for their application.

Bacitracin-resistant Staphylococcus aureus induced in chicken gut and in vitro under bacitracin exposure

It is common knowledge that prolonged and excessive use of antibiotics can lead to antimicrobial resistance. However, the characteristics and mechanism of resistant-bacteria induced by clinically recommended and prophylactic dose drugs remain largely unclear. This study aimed to observe the trends of drug resistance of the bacitracin-susceptible Staphylococcus aureus strain FS127 under exposure to bacitracin (BAC), which were induced in vitro and in chicken gut. Antimicrobial susceptibility testing was used to detect the susceptibility of S. aureus induced in vitro and in the chicken gut to gentamicin, chloramphenicol, tetracycline, doxycycline, penicillin and chloramphenicol. The research results showed that bacitracin could induce drug resistance in S. aureus both in vitro and in vivo. The bacitracin-resistance rate of S. aureus isolated from chicken gut was positively correlated with the dose and time of bacitracin administration. The findings revealed that bacitracin-resistant S. aureus induced in vivo had enhanced susceptibility to chloramphenicol but no such change in vitro. Meanwhile, RT-qPCR assay was used to detect the expression levels of vraD, braD, braR and bacA in typical strains with different bacitracin-resistance levels. It was found that BacA may play a key role in the bacitracin resistance of S. aureus. In conclusion, this work reveals the characteristics and mechanism of bacitracin-resistant S. aureus induced by bacitracin in vivo and in vitro respectively.

Challenges in the management of new daily persistent headache at a tertiary headache center-A retrospective real-world evidence study.

In this retrospective cross-sectional real-world evidence study from the Danish Headache Center (DHC), a national tertiary headache center in Denmark, we sought to identify potential pharmacological agents for the treatment of new daily persistent headache (NDPH). NDPH is an enigmatic headache disorder with abrupt onset and chronic duration for which evidence-based treatments are lacking. NDPH is a diagnosis of exclusion, for which secondary headaches must be ruled out and the etiology remains idiopathic. The sparse investigations of this disorder have not yielded a pathophysiological basis and no effective treatment for NDPH has been found. All patients with an NDPH diagnosis at the DHC were enrolled (n = 64). First, we reviewed the records of all patients with an NDPH diagnosis to evaluate whether they fulfilled the diagnostic criteria. Next, we extracted all the trialled acute and prophylactic pharmacological interventions for the included patients. Then, pharmacological interventions that had been tried in ≥ 20 patients were analyzed post hoc with efficacy as the outcome, which was stratified in five effect categories ("no effect," "partial effect," "full effect," "partial effect and cessation due to adverse events," and "full effect and cessation due to adverse events"). Descriptive statistical analysis was performed, and the results were schematically presented (see Table2). Fifty-one patients out of 64 were found to fulfill NDPH criteria and were included in the study. The drugs tried by ≥ 20 patients were amitriptyline (n = 34), candesartan (n = 27), and mirtazapine (n = 20). No patients experienced a complete effect with these drugs while 9% (3/34), 26% (7/27), and 15% (3/20) experienced a partial effect with no adverse events that led to treatment discontinuation, respectively. The remaining patients experienced either no effect or a partial effect with adverse events leading to treatment discontinuation. In this study we add real-world evidence to suggest that prophylactic drugs conventionally used for treating chronic migraine and chronic tension-type headache have limited utility for treating NDPH; however, a partial response in 26% of patients using candesartan and 15% of patients using mirtazapine warrants further investigation in randomized double-blinded placebo-controlled trials.

Impact of prophylactic echinocandin on the development of neurological complications in patients receiving busulfan-containing conditioning regimens for stem cell transplantation: A single-center retrospective study.

Although neurotoxicity is a major adverse event associated with busulfan, little information is available regarding the association between drug interactions and neurological symptoms during busulfan-based regimens. This study evaluated the association between prophylactic echinocandins and neurological complications in patients receiving busulfan-containing conditioning regimens for stem cell transplantation. We retrospectively included consecutive patients who administered intravenous busulfan as a conditioning regimen at our facility between 2007 and 2022. Prophylactic echinocandin use was defined as the use of an echinocandin antifungal drug to prevent invasive fungal disease in SCT recipients. The primary outcome was the incidence of neurological complications within 7 days of busulfan initiation and was compared between the echinocandin group (patients received prophylactic echinocandin) and nonechinocandin group (patients received prophylactic antifungal drugs other than echinocandin and those without antifungal prophylaxis). Among the 59 patients included in this study, the incidence of neurological complications in the echinocandin (n = 26) and nonechinocandin groups (n = 33) was 30.8% and 63.6%, respectively. We observed a negative association between prophylactic echinocandin use and the development of neurological complications after adjusting for the propensity score for receiving prophylactic echinocandins (adjusted odds ratio 0.294, 95% confidence interval 0.090 to 0.959). We observed a lower incidence of neurological complications in the echinocandin group than in the nonechinocandin group. Our results suggested that the choice of antifungal prophylaxis is associated with busulfan neurotoxicity.

Emphasizing the Importance of Naproxen Prophylaxis May Decrease the Rate of Heterotopic Ossification After Hip Arthroscopy

To investigate the incidence of heterotopic ossification (HO) in patients prescribed prophylactic nonsteroidal anti-inflammatory drugs (NSAIDs), both before and after the introduction of a standardized education protocol. A retrospective review was conducted using a database of hip arthroscopy patients treated by a single surgeon at an academic hospital from 2015 to 2023. The inclusion criteria were (1) primary hip arthroscopy for the treatment of femoroacetabular impingement, (2) completion of a 2-week course of prophylactic postoperative NSAIDs (500 mg of naproxen twice daily), and (3) availability of follow-up radiographs at the 6-month postoperative visit. The control cohort was merely prescribed the postoperative prophylactic NSAIDs, whereas the intervention cohort also received dedicated in-person education, emphasizing the importance of NSAID adherence. The presence of HO was determined through review of follow-up radiographs. Standard descriptive statistics were used to describe the findings. Both the control and intervention groups consisted of 200 continuous hip arthroscopy patients, with the control group treated from 2015 to 2017 and the intervention group treated from 2020 to 2023. Within the control group, 10 cases of HO (5%) were detected. Within the intervention group, 2 cases of HO (1%) were found. The Pearson χ2 test with Yates continuity correction produced a value of 4.21, with a P value of .04. In this study, we found a significantly lower incidence rate of HO in patients who received standardized education on the importance of NSAID compliance versus those who did not. This finding suggests that patient education may play a contributory role in reducing the incidence of HO after hip arthroscopy. Level III, comparative cohort study.

Efficacy of Personalized Postoperative Epilepsy Management in Patients with Glioblastoma Utilizing IDH1 Gene Assessment.

We explored the correlation between the presence of isocitrate dehydrogenase-1 (IDH1) mutations and the incidence of postoperative epilepsy in patients with glioblastoma, as well as assessed the efficacy of preemptive administration of antiepileptic medications in mitigating the occurrence of postoperative epilepsy. Fifty-three patients who received a postoperative pathological diagnosis of glioblastoma, were enrolled in this study. Tumor specimens were subjected to IDH1 gene analysis. The patient cohort was stratified based on their IDH1 mutation status and the administration of prophylactic antiepileptic drugs during the postoperative phase. We subsequently conducted a comparative analysis of postoperative epileptic complications within each patient subgroup. In the cohort of 53 patients under study, the occurrence of epilepsy was observed in 10 out of 21 patients carrying IDH1 mutations, while 5 out of 32 patients with wild-type IDH1 also experienced epilepsy, revealing a statistically significant difference (P < 0.05). Among the 27 patients who received prophylactic antiepileptic drugs, 6 of them developed epilepsy, whereas 9 out of 26 patients who did not receive prophylactic antiepileptic drugs exhibited concurrent epilepsy, with no statistically significant difference (P > 0.05). However, when performing a subgroup analysis, it was found that 3 out of 12 patients with IDH1 mutations who received prophylactic antiepileptic drugs experienced epilepsy, whereas 7 out of 9 patients who did not receive prophylactic antiepileptic drugs developed epilepsy, demonstrating a statistically significant difference (P < 0.05). Furthermore, within the group of 15 patients with wild-type IDH1, 3 patients who received prophylactic antiepileptic drugs developed epilepsy, while 2 cases of epilepsy occurred among the 17 patients who did not receive prophylactic antiepileptic drugs, with no statistically significant difference (P > 0.05). In individuals with IDH1 mutant glioblastoma who have undergone surgical resection, the implementation of preventive antiepileptic therapy demonstrates a potential to diminish the occurrence of postoperative epilepsy.

Investigation of Prophylactic Drug Use Adherence in Patients with Migraine

Investigation of Prophylactic Drug Use Adherence in Patients with Migraine

Anti-CGRP-based Migraine Medications: A Comprehensive Overview

In the early 1990s, the neuropeptide calcitonin gene-related peptide (CGRP) was identified as a key messenger in the pathophysiology of migraine and emerged as a treatment target, fundamentally transforming our approach to migraine therapy. While previous prophylactic drugs were non-specific and often caused intolerable side effects, the discovery of CGRP marked the advent of a new era in migraine treatment. The two main classes of CGRP-specific migraine treatments are monoclonal antibodies that bind to CGRP or the CGRP receptor, and CGRP receptor antagonists, the so-called gepants. Extensive clinical trials have conclusively demonstrated the safety, tolerability, and efficacy of monoclonal CGRP(-receptor) antibodies in the prophylactic treatment of both episodic and chronic migraine. The same positive results apply to the use of various gepants. They have proven to be not only an effective alternative to triptans in acute migraine therapy but also promising options for continuous use as prophylactic treatments. In this review, we aim to present the current state of research on CGRP-specific migraine therapy and insights in real-world data from the first years after their launch in clinical practice.

Ginsenoside Rh4 alleviates idiopathic pulmonary fibrosis by enhancing the CXCL9–CXCR3 axis

AbstractIdiopathic pulmonary fibrosis (IPF), often likened to a “tumor‐like disease,” proves more lethal than several malignancies. Although prior studies have demonstrated the lung‐protective efficacy of ginsenosides, the precise mechanism underlying their alleviative effect on IPF remains elusive. In this study, we validated the efficacy of the ginsenoside Rh4 in alleviating IPF and delved into the underlying mechanisms. Our data showed that Rh4 intervention significantly reduced mortality and hydroxyproline (HYP) content in mice. It also alleviated the pathological process of IPF by ameliorating phenomena such as alveolar wall thickening induced by IPF. In addition, in vitro cellular experiments confirmed that ginsenoside Rh4 was effective in alleviating transforming growth factor‐β1‐induced IPF model. Further analysis showed that ginsenoside Rh4 significantly reduced collagen fiber production and deposition while inhibiting the coagulation cascade signaling pathway. In addition, ginsenoside Rh4 inhibited the epithelial‐mesenchymal transition(EMT) pathway by promoting the CXCR3‐CXCL9 axis, which ultimately alleviated IPF. In conclusion, our data strongly suggest that ginsenoside Rh4 has the potential to be an innovative prophylactic drug against IPF.

Профилактический эффект ингибитора карбоангидразы на повышение внутриглазного давления после интравитреальных инъекций анти-VEGF препарата

Purpose. To evaluate the effect of a carbonic anhydrase inhibitor (brinzolamide 1%) on the short-term increase of intraocular pressure (IOP) after intravitreal injections (IVI) of an anti-VEGF drug in patients with neovascular AMD (nAMD). Material and methods. This study included 60 patients with newly diagnosed nAMD. In group 1 (30 people), prophylactic drugs were not used; in group 2 (30 people), brinzolamide 1% was instilled twice the day before the injection (at 8 pm) and on the day of injection 2 hours before the procedure (at 8 am). IOP was measured with an ICare Pro before IVI (T0), 1 minute after IVI (T₁), 30 minutes (T₂), 60 minutes (T₃). Results. Dynamic changes of IOP in all groups occurred with the same pattern: IOP increased immediately after IVI of the anti-VEGF drug, after 30 minutes IOP decreased and returned to the initial IOP level over the next 60 minutes. Brinzolamide 1% led to a statistically significant decrease in IOP immediately after injection during the first IVI by an average of 3.84 ± 5.1 [95 % CI 1.58–6.1] mm Hg. compared with the control group (p &lt; 0.001), during the second IVI by 5.26 ± 5.7 [95 % CI 2.86–7.66] mm Hg (p &lt; 0.001), by 5.49 ± 5.8 [95 % CI 3.1–7.88] mm Hg (p &lt; 0.001) during the third IVI. Conclusions. Prophylactic instillation of carbonic anhydrase inhibitor (brinzolamide 1%) twice led to a statistically significant decrease in ocular hypertension immediately after IVI of anti-VEGF drug compared to the control group over three loading injections. Keywords: anti-VEGF drug, intraocular pressure, carbonic anhydrase inhibitor

Effects of prophylactic drug therapies and anti-calcitonin peptide-related monoclonal antibodies on subjective sleep quality: An Italian multicenter study

Objective/backgroundsleep alterations strongly influence migraine severity. Prophylactic therapies have a major impact on migraine frequency and associated symptoms. The study purpose was to compare the impact of oral drug therapies or gene-related anti-calcitonin monoclonal antibodies (anti-CGRP mAbs) on sleep alterations. We also evaluated which drug therapies are more effective on sleep quality and the different impact on migraine frequency and life quality. Patients/methodsthis is a multicenter, prospective study conducted in three specialized headache centers (Marche Polytechnic University, Ancona; University of Palermo, Palermo; Fondazione Policlinico Campus Bio-Medico, Rome). At baseline, we assigned migraine patients to preventive therapy with first-line drugs or anti-CGRP mAbs. The Pittsburgh Sleep Quality Index (PSQI) and Migraine Disability Assessment (MIDAS) scales were administered. After three months, we re-evaluated the patients with the same scales. Results214 patients were enrolled. Any prophylaxis was significantly associated with a reduction in PSQI score (mean difference 1.841; 95%CI:1.413–2.269; p < 0.0001), most significantly in the anti-CGRP mAb group (mean difference 1.49; 95%CI:2.617-0.366; p = 0.010). Anti-CGRP mAbs resulted in significant improvement in migraine severity and MIDAS scores. Among oral therapies, calcium antagonists and antidepressants were the most effective in reducing PSQI score between T0 and T1 (p = 0.042; p = 0.049; p < 0.0001, respectively). Conclusionsanti-CGRP mAbs revitalized the management of migraine with stable and well-documented efficacy. Our data also suggest that anti-CGRP mAbs result in a positive effect on sleep quality, with a significant improvement in PSQI scores. Knowing the relevant impact of sleep disruption on migraine severity, these data could help for the management of migraine patients.

Nasal delivery of encapsulated recombinant ACE2 as a prophylactic drug for SARS-CoV-2

Angiotensin-converting enzyme 2 (ACE2) is responsible for cell fusion with SARS-CoV viruses. ACE2 is contained in different areas of the human body, including the nasal cavity, which is considered the main entrance for different types of airborne viruses. We took advantage of the roles of ACE2 and the nasal cavity in SARS-CoV-2 replication and transmission to develop a nasal dry powder. Recombinant ACE2 (rhACE2), after a proper encapsulation achieved via spray freeze drying, shows a binding efficiency with spike proteins of SARS-CoV-2 higher than 77 % at quantities lower than 5 µg/ml. Once delivered to the nose, encapsulated rhACE2 led to viability and permeability of RPMI 2650 cells of at least 90.20 ± 0.67 % and 47.96 ± 4.46 %, respectively, for concentrations lower than 1 mg/ml. These results were validated using nasal dry powder containing rhACE2 to prevent or treat infections derived from SARS-CoV-2.

Prophylactic activity of orally administered dry-heat-sterilized Acremonium egyptiacum against Trypanosoma congolense-induced animal African trypanosomosis

Animal African trypanosomosis (AAT) is an important global disease of livestock that causes economic losses of up to 4.5 billion US dollars per year. Thus, eliminating AAT in endemic countries will improve agricultural productivity and economic growth. To prevent AAT, vector control and the development of prophylactic drugs are crucial. Ascofuranone (AF) is a bioactive fungal compound with proven in vitro trypanocidal potency and in vivo treatment efficacy. However, the complex stereoselective synthesis of AF has prevented its cost-effective industrial production. Recently, a genetically modified strain of Acremonium egyptiacum fungus that produces a high yield of AF was developed. Therefore, we hypothesized that the oral administration of the AF-producing fungus itself may be effective against AAT. Hence, this study aimed to evaluate the prophylactic activity of orally administered dry-heat-sterilized A. egyptiacum against Trypanosoma congolense IL3000 infection using a mouse model. The survival rate was significantly prolonged (p = 0.009), and parasitemia was suppressed in all AF-fungus-treated groups (Group 1–9) compared with that in the untreated control group (Group 10). Hence, the trypanocidal activity of AF was retained after dry-heat-sterilization of the AF-producing fungus and that its oral administration effectively prevented AAT. Since AAT is endemic to rural areas with underdeveloped veterinary infrastructure, dry-heat-sterilized A. egyptiacum would be the most cost-effective potential treatment for AAT.

Construction of an infectious clone for enterovirus A89 and mutagenesis analysis of viral infection and cell binding.

Enterovirus A89 (EV-A89) is an unconventional strain belonging to the Enterovirus A species. Limited research has been conducted on EV-A89, leaving its biological and pathogenic properties unclear. Developing reverse genetic tools for EV-A89 would help to unravel its infection mechanisms and aid in the development of vaccines and anti-viral drugs. In this study, an infectious clone for EV-A89 was successfully constructed and recombinant enterovirus A89 (rEV-A89) was generated. The rEV-A89 exhibited similar characteristics such as growth curve, plaque morphology, and dsRNA expression with parental strain. Four amino acid substitutions were identified in the EV-A89 capsid, which were found to enhance viral infection. Mechanistic studies revealed that these substitutions increased the virus's cell-binding ability. Establishing reverse genetic tools for EV-A89 will significantly contribute to understanding viral infection and developing anti-viral strategies.IMPORTANCEEnterovirus A species contain many human pathogens and have been classified into conventional cluster and unconventional cluster. Most of the research focuses on various conventional members, while understanding of the life cycle and infection characteristics of unconventional viruses is still very limited. In our study, we constructed the infectious cDNA clone and single-round infectious particles for the unconventional EV-A89, allowing us to investigate the biological properties of recombinant viruses. Moreover, we identified key amino acids residues that facilitate EV-A89 infection and elucidate their roles in enhancing viral binding to host cells. The establishment of the reverse genetics system will greatly facilitate future study on the life cycle of EV-A89 and contribute to the development of prophylactic vaccines and anti-viral drugs.

Evaluation of the risk factors for the failure of a single prophylactic dose of anticholinergic drugs for irinotecan-induced cholinergic symptoms.

Irinotecan (IRI) is an anticancer drug that is frequently used to treat colorectal, gastric, and pancreatic cancers. Its side effects include cholinergic symptoms, such as diarrhea, abdominal pain, nausea, and hyperhidrosis. Anticholinergic medicines are frequently used for treatment or prophylaxis; however, the risk factors for the failure of a single prophylactic anticholinergic administration remain unclear. Moreover, an appropriate anticholinergic drug for prophylaxis remains unknown. Thus, we aimed to identify the risk factors associated with the failure of a single prophylactic dose of anticholinergic drugs for IRI-induced cholinergic symptoms and to evaluate the usefulness of multiple prophylactic doses of anticholinergic drugs. Patients who underwent IRI treatment for colorectal, gastric, or pancreatic cancer and received prophylactic anticholinergic drugs for IRI-induced cholinergic symptoms (n = 135) were retrospectively evaluated. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for failure of a single prophylactic dose of anticholinergic drugs. We also evaluated the efficacy of multiple prophylactic anticholinergic drug administration. Based on univariate and multivariate analyses, colorectal cancer, female sex, and prophylactic use of scopolamine butyl bromide were identified as risk factors for failure of a single prophylactic dose of anticholinergic drugs. The efficacy of multiple prophylactic doses was confirmed to be 95% of the patients who had a single prophylactic failure due to temporary effect but symptom appearance after a certain period of time (wearing-off). We determined that colorectal cancer, female sex, and prophylactic use of scopolamine butyl bromide were risk factors associated with the failure of a single prophylactic dose of anticholinergic drugs, and that multiple prophylactic doses for wearing-off can be a promising method.