Alternative Agent For Treatment Research Articles

REVIEW: THE POTENTIAL OF HERBAL PLANTS AS ANTI-ALOPECIA MEDICINES

Hair loss, or alopecia, is a common dermatological condition that affects up to 2% of the world's population. It is often caused by genetic factors, such as male or female pattern baldness, but can also be attributed to various environmental factors, an imbalanced diet, or chronic illnesses. While hair loss is not life-threatening, it can lead to significant anxiety, depression, and other psychological issues, ultimately affecting one's quality of life. Various treatments for baldness, including synthetic drugs like minoxidil and finasteride, or herbal remedies, have been approved by the Food and Drug Administration. Although synthetic drugs are effective, they may come with potential side effects. Natural remedies have been proposed as a viable option for treating baldness because many chronic disorders can lead to alopecia. Therefore, this review focuses on identifying efficient alternative treatment agents with limited side effects. Specifically, it considers medicinal plants as potential healing agents for treating baldness. To gather relevant information for this study, several databases were searched, including Scopus, PubMed, and Google Scholar. Comprehensive searches were conducted using various search terms, such as "baldness," "alopecia," "natural remedies for baldness," "herbal treatment for baldness," and others, to extract relevant scientific articles. Many medicinal plants and natural compounds have shown potential for reducing baldness, thanks to their anti-inflammatory and antioxidant properties. According to existing literature, extracts of medicinal plants and formulations derived from plants, such as Eclipta alba (L.) Hassk, Arctium lappa L., Centella asiatica L., Morinda citrifolia, Acorus calamus var. angustatus, Alpinia zerumbet, ...

Central Nervous System Antimicrobial Exposure and Proposed Dosing for Anthrax Meningitis.

The high mortality of systemic anthrax is likely a consequence of the severe central nervous system inflammation that occurs in anthrax meningitis. Effective treatment of such infections requires, at a minimum, adequate cerebrospinal fluid (CSF) antimicrobial concentrations. We reviewed English medical literature and regulatory documents to extract information on serum and CSF exposures for antimicrobials with in vitro activity against Bacillus anthracis. Using CSF pharmacokinetic exposures and in vitro B. anthracis susceptibility data, we used population pharmacokinetic modeling and Monte Carlo simulations to determine whether a specific antimicrobial dosage would likely achieve effective CSF antimicrobial activity in patients with normal to inflamed meninges (ie, an intact to markedly disrupted blood-brain barrier). The probability of microbiologic success at achievable antimicrobial dosages was high (≥95%) for ciprofloxacin, levofloxacin (500 mg every 12 hours), meropenem, imipenem/cilastatin, penicillin G, ampicillin, ampicillin/sulbactam, doxycycline, and minocycline; acceptable (90%-95%) for piperacillin/tazobactam and levofloxacin (750 mg every 24 hours); and low (<90%) for vancomycin, amikacin, clindamycin, and linezolid. Prompt empiric antimicrobial therapy of patients with suspected or confirmed anthrax meningitis may reduce the high morbidity and mortality. Our data support using several β-lactam-, fluoroquinolone-, and tetracycline-class antimicrobials as first-line and alternative agents for treatment of patients with anthrax meningitis; all should achieve effective microbiologic exposures. Our data suggest antimicrobials that should not be relied on to treat suspected or documented anthrax meningitis. Furthermore, the protein synthesis inhibitors clindamycin and linezolid can decrease toxin production and may be useful components of combination therapy.

Evaluation of the Antiparasitic, Antihepatotoxicity, and Antioxidant Efficacy of Quercetin and Chitosan, Either Alone or in Combination, against Infection Induced by Giardia lamblia in Male Rats.

Giardia lamblia (G. lamblia) is one of the most common protozoal infections and a key cause of malabsorption, some cases of mental developmental issues in children, and reduced body weight. The known antiparasitic medications, which are the standard drugs used for parasitic treatment, have several side effects and sometimes exhibit low efficacy. Therefore, the current study aimed to evaluate the treatment with quercetin (QC) or chitosan (CH), either alone or in combination, as possible alternative therapeutic agents that may alleviate the side effects of G. lamblia infections and restore the normal architecture of the intestinal muscles. They are investigated as alternatives to other routinely administered drugs that may gradually lose their efficacy due to human resistance to therapeutic agents. This study was carried out on 50 male albino rats that were divided into five groups with 10 rats in each group: the control group (Group I), the infected non-treated group (Group II), the infected group treated with QC (Group III), the infected treated group with CH (Group IV), and the infected group treated with a combination of QC and CH (Group V). The effect was first evaluated by counting the G. lamblia fecal cysts in the stool, examining histopathological sections of the intestine with the appearance of trophozoites in the infected group, and conducting a transmission electron microscopic examination of the tissues of the small intestine. Alterations in the biochemical parameters of liver and kidney function and the antioxidant enzymes in the liver tissues of SOD, CAT, and GSH, and non-enzymatic markers of lipid peroxidation (MDA) were evaluated. The results showed a significant decline in the number of parasites in the stool samples, with a marked elevation in the number of trophozoites in the intestinal sections of the infected non-treated group as compared to the infected treated groups. The last group, which was treated with a combination of QC and CH, showed the best results in terms of a decline in the infection rate of G. lamblia in stool samples, with a marked and clear improvement in the intestinal mucosa, regular muscles with normal enteric ganglions, and reduced rates of intestinal injuries caused by G. lamblia trophozoites. Both QC and CH had non-toxic effects on the biochemical parameters of the liver and kidneys, as well as pronounced antioxidant activities due to the elevation of SOD, CAT, and GSH in conjunction with a decline in the levels of MDA. A combination of QC and CH can be considered a potent antiparasitic, anti-hepatotoxic, and antioxidant therapeutic agent; it could constitute a promising alternative treatment agent against G. lamblia infection.

Guiding antimicrobial stewardship through thoughtful antimicrobial susceptibility testing and reporting strategies: an updated approach in 2023.

Antimicrobial susceptibility test and report guidelines are an important tool for antimicrobial stewardship programs. Since 1972, Tables 1 within the Clinical and Laboratory Standards Institute (CLSI) M100 document have provided a general framework upon which clinical microbiologists and antimicrobial stewardship teams can build algorithms for susceptibility testing and reporting that meet the specific needs of their institution. Many changes were made to Tables 1 in M100-Ed33 to modernize the content to reflect the landscape of current clinical practice, including the growing armamentarium of antimicrobial agents, the emergence of new mechanisms of antimicrobial resistance, the increasing prevalence of infections caused by multidrug-resistant organisms, and updated consensus recommendations for first-choice and alternative agents for treatment. With these items in mind, the CLSI Table 1 ad hoc working group revised Tables 1 with the ultimate goal of supporting institutions in the creation of individualized test and report strategies that support local antimicrobial stewardship program initiatives. These strategies are built on the concepts of selective and cascade reporting. This minireview introduces the concept of CLSI M100-Ed33 Tables 1, describes the changes to Tables 1 introduced in 2023, and provides clinical vignettes that demonstrate how Tables 1 can be used in various scenarios to devise antimicrobial susceptibility test and report strategies.

Is tannic acid a promising option in local treatment of nasal diseases?

We investigated the effects of tannic acid on viability and proliferation of nasal cells after topical application. It was also evaluated whether tannic acid served as an alternative treatment agent. Collected primary nasal epithelium from healthy people who had undergone septoplasty operations were incubated in cell culture. Following the implementation of 2.5 µM tannic acid in cultured cells, both the number of total cells and their viability were measured using the trypan blue assay, while proliferation was assessed through the XTT method. The XTT method, which involves using "2,3-bis-(2-methoxy-4-nitro-5-sulphophenyl)-2H-tetrazolium-5-carboxanilide", is a reliable means of determining cellular toxicity. XTT experiment results showed that there was no harm was detected to nasal cells after tannic acid's topical implementation. There were no significant changes in cell proliferation; moreover, no matter what the doses were. Additionally, no cytotoxic effects were detected on nasal cells' primary culture at "the end of the 24 hours of implementation". There was no side effect of it, either. According to the research, the application of tannic acid topically did not result in any harmful effects on the nasal cell culture. Tannic acid's potential anti-inflammatory properties and its ability to decrease Th2-related cytokines suggest that it may be beneficial for patients with rhinosinusitis or allergic rhinitis, pending confirmation through clinical trials. Additionally, if clinical trials confirm its effectiveness, tannic acid may be useful in healing wounds for patients undergoing septorhinoplasty.

Phytic Acid Demonstrates Rapid Antibiofilm Activity and Inhibits Biofilm Formation When Used as a Surface Conditioning Agent.

Root canal infections are associated with biofilms and are treated with chemical irrigants with a high success rate. However, treatment failure does arise, which is attributed primarily to resistance exhibited by biofilms. Currently used irrigants in root canal treatment have disadvantages, and there is therefore a need for more biocompatible alternatives with antibiofilm properties to reduce root canal treatment failure and complications. The aim of this study was to evaluate the in vitro antibiofilm properties of phytic acid (IP6), which is a potential alternative treatment agent. Single- and dual-species biofilms of Enterococcus faecalis and Candida albicans were developed on the well surfaces of 12-well plates and on hydroxyapatite (HA) coupons, and then exposed to IP6. In addition, selected HA coupons were preconditioned with IP6 before biofilm development. IP6 demonstrated bactericidal effects and altered the metabolic activity of biofilm cells. Confocal laser-scanning microscopy showed that IP6 caused significant and rapid reduction in live biofilm cells. At sublethal concentrations, IP6 did not alter the expression of tested virulence genes except for C. albicans hwp1, the expression of which was upregulated but not reflected by a change in hyphal transformation. IP6-preconditioned HA coupons led to extensive inhibition of dual-species biofilm formation. The results of this study highlight for the first time the antibiofilm inhibitory properties of IP6 and the potential for its exploitation in several clinical applications. IMPORTANCE Root canal infections are biofilm associated, and despite mechanical and chemical treatment procedures, infection recurrence occurs, and this is likely due to the high tolerance of associated biofilms to antimicrobials. The currently used treatment agents have several disadvantages, which necessitates the search for new improved agents. In this study, the natural chemical phytic acid was found to exhibit antibiofilm activity against established mono and dual mature biofilms over a short contact time. Most importantly, phytic acid was found to cause significant inhibition of dual-species biofilm formation when used as a surface preconditioning agent. The findings of this study identified a novel use of phytic acid as a potential antibiofilm agent that can be used in several clinical applications.

Clinical characteristics, microbiology and outcomes of a cohort of patients treated with ceftolozane/tazobactam in acute care inpatient facilities, Houston, Texas, USA.

Ceftolozane/tazobactam is a β-lactam/β-lactamase inhibitor combination with activity against a variety of Gram-negative bacteria, including MDR Pseudomonas aeruginosa. This agent is approved for hospital-acquired and ventilator-associated bacterial pneumonia. However, most real-world outcome data come from small observational cohorts. Thus, we sought to evaluate the utilization of ceftolozane/tazobactam at multiple tertiary hospitals in Houston, TX, USA. We conducted a multicentre retrospective study of patients receiving at least 48 h of ceftolozane/tazobactam therapy from January 2016 through to September 2019 at two hospital systems in Houston. Demographic, clinical and microbiological data were collected, including the infecting bacterial isolate, when available. The primary outcome was composite clinical success at hospital discharge. Secondary outcomes included in-hospital mortality and clinical disposition at 14 and 30 days post ceftolozane/tazobactam initiation. Multivariable logistic regression analysis was used to identify predictors of the primary outcome and mortality. Recovered isolates were tested for susceptibility to ceftolozane/tazobactam and underwent WGS. A total of 263 patients were enrolled, and composite clinical success was achieved in 185 patients (70.3%). Severity of illness was the most consistent predictor of clinical success. Combination therapy with ceftolozane/tazobactam and another Gram-negative-active agent was associated with reduced odds of clinical success (OR 0.32, 95% CI 0.16-0.63). Resistance to ceftolozane/tazobactam was noted in 15.4% of isolates available for WGS; mutations in ampC and ftsI were common but did not cluster with a particular ST. Clinical success rate among this patient cohort treated with ceftolozane/tazobactam was similar compared with previous experiences. Ceftolozane/tazobactam remains an alternative agent for treatment of susceptible isolates of P. aeruginosa.

Synergistic Antibacterial Activity of 1-Methyl Ester-Nigericin and Methyl 5-(Hydroxymethyl) Furan-2-Carboxylate Against Proteus spp.

&lt;b&gt;Background and Objective:&lt;/b&gt; Synergistic combinations of antimicrobial agents with different mechanisms of action are successful approaches for combating bacterial infections. This study aimed to evaluate the synergistic effect of 1-methyl ester-nigericin &lt;b&gt;(1)&lt;/b&gt; and methyl 5-(hydroxymethyl) furan-2-carboxylate &lt;b&gt;(2)&lt;/b&gt; against &lt;i&gt;Proteus&lt;/i&gt; spp., isolates. &lt;b&gt;Materials and Methods:&lt;/b&gt; The synergistic antimicrobial activity of the compounds was tested by the checkerboard method and time-kill curves. To estimate the interaction between the compounds, the Fractional Inhibitory Concentration Index (FICI) of the combination was calculated. The cytotoxic activity of the compounds in combination was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay on LLC-MK2 cell lines. The reduction percentage of biofilms was obtained using the colourimetric method. &lt;b&gt;Results:&lt;/b&gt; The MIC values for compounds &lt;b&gt;1&lt;/b&gt; and &lt;b&gt;2&lt;/b&gt; against test bacteria ranged from 39.06-78.12 μg mL&lt;sup&gt;1&lt;/sup&gt; and from 78.12-156.25 μg mL&lt;sup&gt;1&lt;/sup&gt;, respectively. The MIC was reduced to 1-8th as a result of the combination of compounds &lt;b&gt;1&lt;/b&gt; and &lt;b&gt;2&lt;/b&gt;. After 4-24 hrs of treatment with ½ MIC of compounds &lt;b&gt;1&lt;/b&gt; and &lt;b&gt;2&lt;/b&gt;, the killing rate (in CFU mL&lt;sup&gt;1&lt;/sup&gt;) increased to a greater degree than observed with either test compound alone. The combination of compounds &lt;b&gt;1&lt;/b&gt; and &lt;b&gt;2&lt;/b&gt; showed a synergistic effect with FICI of 0.50 and 0.28. The synergistic combination of compounds &lt;b&gt;1&lt;/b&gt; and &lt;b&gt;2&lt;/b&gt; was effective on the biofilm reduction of &lt;i&gt;Proteus&lt;/i&gt; &lt;i&gt;vulgaris&lt;/i&gt; NP16 (85.72%) and NP47 (89.14%). &lt;b&gt;Conclusion:&lt;/b&gt; This study recommends compounds &lt;b&gt;1&lt;/b&gt; and &lt;b&gt;2&lt;/b&gt; in combination as a potential alternative treatment agent for &lt;i&gt;Proteus&lt;/i&gt; spp. infections.

Phenazopyridine-Induced Methaemoglobinaemia The Aftermath of Dysuria Treatment.

IntroductionPhenazopyridine is an over-the-counter urinary analgesic commonly used to alleviate the burning and urgency associated with lower urinary tract infections. Methaemoglobinaemia is an uncommon adverse effect of phenazopyridine use. We report a case of methaemoglobinaemia in a patient prescribed daily phenazopyridine to treat urethral and bladder irritation caused by a chronic indwelling Foley catheter.Case descriptionA 55-year-old female resident of a long-term acute care facility with a chronic Foley, tracheostomy and ventilator-dependent respiratory failure was observed to have generalized dusky skin and hypoxia. Pulse oximetry was reading in the high 80s despite administration of 100% FiO2. ABG revealed paO2 of 451, oxyhaemoglobin level 75% and methaemoglobin level 22%. Medication review indicated that the patient was prescribed phenazopyridine 400 mg TID for the previous 2 months. This medication was discontinued. Considering she was chronically taking mirtazapine, she can increase risk of serotonin syndrome should she be administered first-line treatment with methylene blue. Vitamin C was thus instead administered as a second-line agent. Serial ABGs showed a rapid decline in methaemoglobin levels and an increase in oxyhaemoglobin within 2 days.DiscussionAcquired methaemoglobinaemia is a rare adverse effect of treatment with phenazopyridine. This risk increases when drug dosage and duration exceed manufacturer specifications. Treatment typically includes cessation of the offending drug and administration of methylene blue in severe cases. A thorough medication reconciliation should be performed prior to methylene blue initiation, as patients taking serotonergic medications (for example, MAOIs, SSRIs, SNRIs, TCAs) are at increased risk of serotonin toxicity with co-administration of methylene blue. In these instances, ascorbic acid/vitamin C can be chosen as an alternative treatment agent.ConclusionWork-up of refractory hypoxia should involve a thorough review of medications as even some over-the-counter drugs can cause the fatal side effect of methaemoglobinaemia. Treatment with vitamin C should be considered over methylene blue if serotonergic medications have been recently prescribed in order to avoid risk of serotonin syndrome.LEARNING POINTSMethaemoglobinaemia is an uncommon, life-threatening adverse effect of phenazopyridine use. Presentation depends on the severity of the disorder, ranging from headache, weakness, lightheadedness and dyspnoea, to arrhythmias, confusion, seizures and multiorgan failure.Workup of refractory hypoxia should involve a comprehensive medication review as even some over-the-counter drugs can cause methaemoglobinaemia.Management of methaemoglobinaemia involves cessation of the offending drug, administration of supplemental oxygen and treatment with methylene blue (1–2 mg/kg) if MetHb >30%, or for symptomatic patients with MetHb >20%. Vitamin C can be used as an alternative agent if there is a contraindication to methylene blue (for example, with patients simultaneously receiving serotonergic medications and/or those with G6PD deficiency).

Lyme Carditis With Complete Heart Block Successfully Treated With Oral Doxycycline.

Lyme disease is a vector-borne infection that can affect multiple different organ systems. Lyme carditis represents one of these sequelae and is defined by acute onset of high-grade atrioventricular block in the presence of laboratory-confirmed infection. Current guidelines recommend patients with Lyme carditis be admitted for close cardiac monitoring and intravenous antibiotics therapy. Our case illustrates an active duty male who was initially diagnosed with Lyme disease after initially reporting symptoms including headache, fever, eye pain, and rash, with subsequent development of exercise intolerance 6 weeks later. An electrocardiogram (ECG) obtained at that time was misinterpreted as first-degree heart block, and he was initiated on oral doxycycline therapy and referred to cardiology. On follow-up to cardiology clinic, the prior ECG was reviewed and interpreted as complete heart block. A repeat ECG showed resolution of the heart block, and exercise stress testing showed chronotropic competence. This case illustrates the resolution of complete heart block in Lyme carditis with oral doxycycline, suggesting this antibiotic as a possible alternative treatment agent.

Investigation of apoptotic activities of NOE on human ovarian cancer cells

Ovarian cancer is one of the most malignan cancers of the reproductive system of womans. Along with the other cancer types, ovarian cancer requires alternative agents for treatment due to the limited efficiency and strong side effects of classical chemotherapeutics and long treatment process. Recently, cancer investigations are focused on intracellular targets for cancer therapy. Sphingolipid molecules, especially ceramides of them are reported as potent targets for cancer therapy. İncreased leves of ceramides into the cancer cells induce apoptosis and this increase can be caused by supressing ceramidases via new generation inhibitors of the enzymes. In this study, NOE (Oleoyl ethanolamide), a ceramidase inhibitor was used to cause cytotoxicity and induce apoptosis in human ovarian cancer cells, OVCAR-3. Our results clearly showed that NOE significantly reduced cell viability and caused cytotoxicity together with morphological changes indicating apoptosis that is proved with the flow cytometry results. NOE is proposed for a candicate for designing anti-cancer agent after further investigations.

In Vitro Antibiotic Activity of red Shallot (Allium ascalonicum), Mulberry (Morus indica), and Marigold (Tagetes erecta) Extracts against Streptococcus pyogenes

Bacterial infection is a major global health concern. One of the critical problems is the widespread of antimicrobial-resistant bacteria from inappropriate and prolonged use of antimicrobial agents in both humans and animals. Plant extracts might afford the chance to replace antibiotic drugs and reduce the emerging of antimicrobial-resistant bacteria. This study aimed to examine the antibiotic activity of ethanolic crude extracts of some Thai medicinal plants grouping in their parts as whole onions of red shallot (Allium ascalonicum), petals of marigold (Tagetes erecta), mulberry leaves, and root barks (Morus indica) to inhibit the growth of Streptococcus pyogenes. The antibiotic activities of the crude extract of three Thai medicinal plants using absolute ethanol were trialed against Streptococcus pyogenes using the disk diffusion method. Erythromycin and Ceftriaxone discs were chosen to be positive control standards as the representative of antibiotic drugs. Each dried plant extracts was prepared to test the inhibition with a concentration at 25, 50, and 75 mg/mL stock solution. The results showed that three groups from all testing groups of Thai medicinal plant extracts had the potential of antibiotic activity against S. pyogenes. The highest antibiotic activity against S. pyogenes was detected from whole onion extract red shallot followed by the extract of the mulberry leaves and root barks of mulberry strain Nakhon Ratchasima 60 (Nak 60) while the extract of marigold petal did not present antibiotic activity. The results revealed that crude extract of those two Thai medicinal plants, including red shallot and mulberry, had antibiotic activity against bacterial growth of S. pyogenes in the experiment and these medical Thai plants had potential benefits for developing as alternative treatment agents for S. pyogenes infections in both humans and animals in the future.

Plasticity and Strength Behaviour of Marine Clay Stabilized with Waste Steel Dust for Soil Improvement Works

Soft marine clay soil is characterized with highly compressible behavior, in which associated with poor bearing capacity and low in shear resistance. Soil improvement works are carried out to reduce the soil failure and destruction to the superstructure. Various techniques available for soil stabilization including the use of admixture to improve the engineering properties of the problematic soil. This paper aims to report on the use of waste steel dust retrieved from the medication supply industry as soil stabilization agent. Several series of Atterberg limit test and Unconfined Compressive Test were carried out to foresee the potential use of the waste steel dust for the purpose of civil engineering applications. The significant findings from this study is evident that the waste steel dust ranges from 5% to 15% did not able to serve as soil stabilization agent. It can reduce the plastic behavior of the soil sample; however, it also caused the strength of the soil declined. In comparison with previous studies, the presence of activated agent could possibly enhance the performance of waste steel dust as an alternative treatment agent to soil improvement works. The use of activated agent is to serve as pozzolanic materials to create cementitious bonding in between the soil interparticles matrix.

Abstract LB-227: Preclinical development and characterization of STI-6129, an anti-CD38 antibody-drug conjugate, as a new therapeutic agent for multiple myeloma

Abstract CD38 is a validated target for the treatment of CD38-overexpressing hematologic malignancies such as multiple myeloma (MM). Daratumumab is the first anti-CD38 mAb drug approved by the FDA for use as single agent and in combination with standard therapies for MM. However, resistance to Daratumumab in both primary and refractory MM patients has been reported. Here we report the preclinical development of STI-6129 (also CD38-077), a CD38-targeting antibody-drug conjugate (ADC), as a new therapeutic agent for MM. STI-6129 consists of a fully human anti-CD38 antibody, STI-5171, identified from the Sorrento G-MAB® antibody library, conjugated to the microtubule inhibitor duostatin-5.2 (Duo-5.2) via a non-polyethylene glycol linker using our site-specific conjugation proprietary C-LOCK technology. STI-5171 binds specifically to CD38-positive but not CD38-negative tumor cell lines with a KD ~ 1.72E-8 M. STI-6129 is internalized into CD38-positive cells at a rate comparable to that of the unconjugated antibody STI-5171. In cytotoxicity studies, STI-6129 exhibited CD38-dependent cytotoxic activity against a panel of CD38-expressing tumor cell lines with the range of EC50 from 5-100 µg/mL. Importantly, STI-6129 does not display cytotoxic activity (EC50 &amp;gt; 150 μg/mL) against normal human PBMCs after 120 hr exposure. Mechanistic evaluation of STI-5171 compared to Daratumumab revealed that this antibody does not induce homotypic aggregation of tumor cells, a cell adhesion response that has been reported to be linked to drug resistance and increased metastatic potential. Further, the anti-tumor activity of STI-6129 showed broad, potent, and CD38-dependent in vivo efficacy in multiple xenograft animal models. Pharmacokinetic evaluation of STI-6129 in Daudi-Fluc tumor-bearing mice revealed that the ADC is stable with half-life (T1/2) of 7-11 days, comparable to that of the unconjugated antibody. The serum concentration of STI-6129 remained above the therapeutically effective level up to 1 week in mice after a single injection at 10 mg/kg. In cynomolgus monkey, the PK profiles of STI-6129 and STI-5171 were nearly identical, further confirming the stability of the ADC in monkey blood circulation.In summary, STI-6129 exhibits potent in vitro and in vivo anti-tumor activities in multiple CD38-positive hematological models. These results warrant further development of STI-6129, potentially as a better or alternative agent for treatment of multiple myeloma. Citation Format: Lingna Li, Andrew Hau, Wenyong Tong, Megan Lau, Tong Zhu, Katherine Fells, Angel Wei, Xiaoqing Li, Dylan Deng, Yingqing Sun, Ernest Kovacs, Alisher Khasanov, Zheng Yan, Panyun Zhu, Heyue Zhou, Henry Ji, Hui Li, Hong Zhang. Preclinical development and characterization of STI-6129, an anti-CD38 antibody-drug conjugate, as a new therapeutic agent for multiple myeloma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-227.

Valproic Acid for the Management of Agitation and Delirium in the Intensive Care Setting: A Retrospective Analysis

PurposeValproic acid has been proposed as an alternative agent for treatment of agitation and delirium in the intensive care unit (ICU). Clinical data to support the use of valproic acid for this indication are limited. The objective of this analysis was to assess the efficacy and safety associated with the use of valproic acid for the management of agitation and delirium in the ICU. MethodsThis retrospective descriptive analysis included patients who were prescribed valproic acid for a minimum of 3 days for the treatment of agitation and/or delirium in the cardiac, surgical, or medical ICU from May 31, 2015 to December 31, 2017. The prevalence of agitation and delirium was assessed during valproic acid therapy for up to 7 days. Additional data analyzed included opioid, sedative, and antipsychotic requirements and safety outcomes. FindingsA total of 47 patients met the inclusion criteria. There was an observed downward trend in the prevalence of agitation (47.8% vs 16.7%) and delirium (84.8% vs. 63.3%) throughout valproic acid therapy. In addition, the proportion of patients who required dexmedetomidine, benzodiazepines, antipsychotics, and opioids decreased while patients were taking valproic acid. No adverse effects attributed to valproic acid occurred in this patient population. ImplicationsValproic acid may be an alternative option to assist in the management of agitation and delirium in the ICU. Additional prospective data are needed to validate the use of this agent for the treatment of agitation and delirium in critically ill patients.

Effect of Zataria multiflora, Satureja, Oak Fruit Husk, and Jaftex Mouthwash on Treatment of Recurrent Minor Oral Aphthous Stomatitis

Context: The use of herbal medications can improve the quality of life and prevent the side effects of chemical drugs. The present narrative review study aimed to assess the efficacy and safety of Zataria multiflora, Satureja, oak fruit husk, and Jaftex herbal mouthwash for the treatment of minor oral aphthous stomatitis. Evidence Acquisition: A literature review was conducted in electronic databases such as PubMed, Web of Science, Scopus, and Google Scholar, as well as Persian databases such as SID, Magiran, and IranMedex from 2000 to 2019, particularly in the last 10 years. The appropriate keywords were searched including “recurrent aphthous stomatitis”, “oak tree”, “Satureja”, “Zataria multiflora”, and “Jaftex mouthwash”. Results: Six clinical trials were analyzed in the present study. The results showed that Zataria multiflora, Satureja, oak fruit husk, and Jaftex mouthwash have beneficial effects on the treatment of recurrent aphthous stomatitis. The main outcome measures assessed in this study were the duration of the complete healing process, ulcer size, and the level of pain. No side effects were reported in Zataria multiflora, oak fruit husk, and Jaftex mouthwash, but Satureja khuzestanica essential oil revealed a trivial burning at the initial time of application. Conclusions: Reviewing these studies indicated that Zataria multiflora, Satureja, oak fruit husk, and Jaftex mouthwash greatly improved the patients’ symptoms by shortening the duration of the complete healing process, reducing ulcer size, and relieving pain. Therefore, these herbal medicines can be used as alternative treatment agents for recurrent aphthous stomatitis. More investigations are required to elucidate the probable mechanism(s) and mode(s) of action of these plants and standardization.

TOWARD NONALCOHOLIC FATTY LIVER TREATMENT; A REVIEW ON HERBAL MEDICINE TREATMENT

This study, review the nonalcoholic fatty liver treatment with emphasis on herbal medicine treatment. The accumulation of the mass of triglycerides by 5% in the liver cells of those who are not alcoholic leads to a situation called nonalcoholic fatty liver disease (NAFLD). Nonalcoholic fatty liver is known as the most common liver disorder in the world, such that its prevalence varies from 3% to 25% in different populations of the world per race, age, sex, place of residence and lifestyle. Numerous studies have been carried out on the NAFLD and its pathological mechanism and are still ongoing. In classification of the causes of fatty liver, two general groups can be noted: (i) an effective group with indirect effects such as hypothyroidism, pituitary hypoplasia, polycystic ovarian syndrome, and sleep apnea; (ii) The other group is directly involved in the development of this disease in individuals such as abdominal obesity, metabolic syndrome and type 2 diabetes. Most patients are asymptomatic and are diagnosed by disturbed liver tests. This disease is the most common cause of liver enzymes disorder after hepatitis and chronic liver disease. In more than three-fourths of patients during a clinical examination, the increased size of liver is visible, and the most common symptom is excessive fatigue, lethargy, and pain in the upper right abdomen. The patients may complain of persistent itching, jaundice or complications caused by the increased portal pressure. If the disease leads to liver cirrhosis, hepatomegaly is seen in most cases. In most cases, the patient only finds out about the fatty liver when a regular blood test (generally liver function tests) shows a problem. Alanine aminotransferase and Aspartate aminotransferase are the most important liver enzymes, and their increase of 1.5-2 times in the tests shows the involvement of liver with this disease. Due to the key role of lipid accumulation in NAFLD progression, inhibition of lipid accumulation is a major focus of anti-NAFLD drug development. A variety of antiNAFLD agents are currently in preclinical development. Additionally, metformin, statins, and fibrates, are currently being tested as NAFLD treatments in clinical trials. This study aims to review medicinal herbs used to treat NAFLD around the world. The obtained results of the present review investigation demonstrated that 27 medicinal herbs were found that traditionally used to treat NAFLD around the world. The most parts of these plants are leaves, root, and flowers, respectively; whereas these medicinal herbs are most commonly used in countries of Asian and African such as Iran, Pakistan, India and South Africa, etc. The results demonstrated that medicinal herbs have universally used to treat NAFLD. Thus, we can consider them as alternative agents for treatment of NAFLD; nevertheless, more investigations are mandatory to elucidate the precise mechanisms and also toxicity of these plants in human subjects. Keywords: fatty liver; plant medicine; treatment; traditional medici

Fisetin effects on cell proliferation and apoptosis in glioma cells.

This research investigated the antiproliferative effects of 1-500 μM fisetin in T98G and BEAS-2B cells by MTT assay. The IC50 of fisetin in T98G cells for 24 and 48 h were 93 and 75 μM, respectively. Apoptotic alterations of fisetin-treated T98G cells were observed by transmission electron microscopy. BEAS-2B was then used in comparison to T98G cells to determine the cytotoxic effects of fisetin. The IC50 of fisetin for 24 and 48 h were recorded as 270 and 90 μM in BEAS-2B cells, respectively. Different concentrations of fisetin were selected to determine the apoptotic and necrotic effects. Consequently, fisetin was determined to have more apoptotic effects in T98G than BEAS-2B cells, dose- and time-dependently. Moreover, fisetin was found to have cytotoxicity at lower doses in T98G cells compared to carmustine, as positive control. CASPASE 3, CASPASE 9, CASPASE 8, and BAX expressions were increased by the selected fisetin doses of 25 and 50 μM, while that of BCL-2 and survivin was reduced in T98G cells. These results will serve as an essential basis of future in vitro and in vivo studies, in the continuous search for alternative treatment agents for gliomas.

Antiviral Activities of Curcuma Genus against Hepatitis C Virus

Hepatitis C virus (HCV) infection is one of the major public health problems in the world. Even though the new agents are shown to increase the sustained virology response, however, there are still many people who cannot access the therapy due to the high cost. Moreover, the emergence of resistance and side effects presented the necessity to develop alternative treatment agents for HCV infection. Plants of the genus of curcuma are popular among traditional medicines in the world, including Indonesia. They have been used for many herb remedies and reported to possess many biological activities. Several plants from the curcuma genus were known as treatment agents in liver disease and jaundice. Our current study determines antiviral activities of Curcuma domestica, Curcuma xanthorrhiza, and Curcuma heyneana against HCV and further examines the mechanism of actions. Antiviral activity was performed by in vitro culture cells using Huh 7.5it cells and treated with the mixture of extract and virus JFH1. The effects of extracts in HCV life cycle were determined by mode of action analysis to examine the action of substances in the entry or post entry steps. The results revealed that ethanol extract of C. domestica, C. xanthorrhiza, and C. heyneana showed strong anti-HCV activities with IC50 values of 1.68 ± 0.05, 4.93 ± 0.42 and 5.49 ± 0.59 μg/mL, respectively without any cytotoxicity effect. Mode of action analysis demonstrated that of C. domestica and C. heyneana exhibit HCV in the entry step, while C. xanthorrhiza inhibit in the entry and post entry steps of HCV life cycle. Docking analysis to predict the interaction of curcumin, the main compound of curcuma genus, revealed a strong interaction between curcumin and 4GAG receptor, a protein involved in the entry step of HCV infection. Moreover, it was also reported to possess good interaction with 4EAW, an HCV NS5B, which plays an important role in HCV replication. These results suggested that C. domestica, C. xanthorrhiza, and C. Heyneana possessed strong inhibition against hepatitis C virus, therefore they may be good candidates for anti-HCV agents.

Ecballium Elaterium Poisoning in Pediatric Emergency Service: A Case Report

Background Ecballium elaterium is the only species belonging to the genus Ecballium of Cucurbitaceae family. It is native to the Mediterranean region. Despite its side effects, E. elaterium has still been being used as an alternative treatment agent for sinusitis, cirrhosis, rheumatic diseases and hemorrhoids for its anti-inflammatory and cathartic actions. Herein we discuss a pediatric case showing gastrointestinal side effects after ingesting E. elaterium. Case Report: A six-year-old boy admitted to Cukurova University Medical Faculty Pediatric Emergency Department, Turkey, for vomiting one hour after ingesting a green plant which he had tasted to satisfy his curiosity. Physical examination, vital signs and laboratory tests revealed normal. The ingested plant was defined to be E. elaterium. Maintenance fluid infusion, 1 mg/kg ranitidine and sucralfate medications were commenced. During the follow-up, the patient developed numbness of the tongue and hyper-salivation, without any signs of uvular edema or other system findings. Further follow-up showed stable vital signs within the normal range with no additional complications. The patient was sent home with the cure and recommendations. Discussion: The plants and herbs that are used as agents of alternative or complementary medicine may as well be accidentally or curiously taken by children leading to unwanted intoxication cases. Pre-encounter actions to prevent such cases are as important as any post-exposure clinical interventions to impede the unwanted consequences. One such measure might be a more intensive public information policy underscoring the fact that plants have the potential to be noxious and may cause serious side effects and even death.