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Annual Review of Microbiology Sep 2023Among endosymbiotic bacteria living within eukaryotic cells, is exceptionally widespread, particularly in arthropods. Inherited through the female germline, it has... (Review)
Review
Among endosymbiotic bacteria living within eukaryotic cells, is exceptionally widespread, particularly in arthropods. Inherited through the female germline, it has evolved ways to increase the fraction of bacterially infected offspring by inducing parthenogenesis, feminization, male killing, or, most commonly, cytoplasmic incompatibility (CI). In CI, infection of males causes embryonic lethality unless they mate with similarly infected females, creating a relative reproductive advantage for infected females. A set of related bicistronic operons encodes the CI-inducing factors. The downstream gene encodes a deubiquitylase or nuclease and is responsible for CI induction by males, while the upstream product when expressed in females binds its sperm-introduced cognate partner and rescues viability. Both toxin-antidote and host-modification mechanisms have been proposed to explain CI. Interestingly, male killing by either or endosymbionts involves deubiquitylases as well. Interference with the host ubiquitin system may therefore be a common theme among endosymbiont-mediated reproductive alterations.
Topics: Female; Male; Humans; Wolbachia; Semen; Reproduction; Cytoplasm; Molecular Biology; Symbiosis
PubMed: 37285552
DOI: 10.1146/annurev-micro-041020-024616 -
BMC Cancer Jul 2023Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/levo-leucovorin (Levo-LV) was approved for unresectable pancreatic cancer (UR-PC) in March 2020 in Japan....
BACKGROUND
Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/levo-leucovorin (Levo-LV) was approved for unresectable pancreatic cancer (UR-PC) in March 2020 in Japan. Levo-LV is administered by intravenous infusion over 120 min following 90 min intravenous infusion of nal-IRI (conventional method), causing a significant burden on both patients and the outpatient chemotherapy room owing to the prolonged administration time. Thus, from July 2021, we introduced the simultaneous intravenous administration of nal-IRI and Levo-LV (parallel method) with the approval of the institutional regimen committee.
METHODS
We retrospectively reviewed the data of 69 patients with UR-PC who received nal-IRI plus 5-FU/Levo-LV at our hospital between June 2020 and October 2021. We examined the safety of the parallel method and compared the treatment outcomes and administration times between the two methods.
RESULTS
The median age was 66 years (54%, male). Disease statuses were locally advanced, metastatic, and postoperative recurrence after pancreatectomy in 7, 50, and 12 patients, respectively. Nal-IRI plus 5-FU/Levo-LV treatment was second and third-line or later in 35 and 34 patients, respectively. No intravenous line problems were observed during the parallel administration of nal-IRI and Levo-LV. Although there were no significant differences in response rates and adverse events between the two methods, the administration time was significantly shorter in the parallel method than in the conventional method.
CONCLUSION
The parallel administration of nal-IRI and Levo-LV is clinically safe and not inferior in efficacy. Moreover, parallel administration may offer convenience to patients and healthcare workers by reducing administration time.
Topics: Humans; Male; Aged; Female; Irinotecan; Levoleucovorin; Retrospective Studies; Leucovorin; Liposomes; Pancreatic Neoplasms; Fluorouracil; Antineoplastic Combined Chemotherapy Protocols; Camptothecin
PubMed: 37518012
DOI: 10.1186/s12885-023-11205-6 -
Critical Reviews in Toxicology Dec 2023Metal phosphides are highly toxic pesticides that result in high morbidities and mortalities worldwide. This systematic review included 350 studies that fulfilled the... (Review)
Review
Metal phosphides are highly toxic pesticides that result in high morbidities and mortalities worldwide. This systematic review included 350 studies that fulfilled the eligibility criteria. There were significant rising trends of studies on acute aluminum phosphide (AlP) and zinc phosphide (ZnP) poisoning (-values = <.001), pointing to an increased number of phosphide-intoxicated patients. Acute AlP poisoning studies represented 81%, 89.3%, and 97.7% of all descriptive, analytical, and experimental interventional studies included in this review, respectively. High AlP poisoning mortality explains great research interest in AlP poisoning. Thus, after 2016, nearly half (49.7%) of studies on acute AlP poisoning were issued. Also, 78.82% of experimental interventional studies on AlP poisoning were published after 2016. The trends of in-vitro, animal, and clinical studies on AlP poisoning significantly increased with -values equal to .021, <.001, and <.001, respectively. Seventy-nine treatment modalities for acute AlP poisoning were pooled from 124 studies; 39 management-related case reports, 12 in-vitro studies, 39 animal studies, and 34 clinical studies. All therapeutic modalities were summarized to formulate an integrated and comprehensive overview. For clinicians, therapeutic modalities significantly decreased mortality of acute AlP poisoning in clinical trials included extracorporeal membrane oxygenation (ECMO), N-acetyl cysteine (NAC), vitamin E, glucose-insulin-potassium (GIK) infusion, fresh packed RBCs infusion, and GIT decontamination using oils. However, meta-analyses are needed to provide solid evidence regarding their efficacies. To date, there is no effective antidote nor evidence-based standardized protocol for managing acute AlP poisoning. This article outlined the potential research gaps in phosphide poisoning that might promote and direct future medical research in this context.
Topics: Animals; Pesticides; Evidence Gaps; Antidotes; Acetylcysteine; Aluminum Compounds
PubMed: 37387512
DOI: 10.1080/10408444.2023.2225539 -
Tidsskrift For Den Norske Laegeforening... May 2024A woman in her seventies presented to the accident and emergency department (A&E) with shortness of breath that had increased over a period of three weeks. She had a...
BACKGROUND
A woman in her seventies presented to the accident and emergency department (A&E) with shortness of breath that had increased over a period of three weeks. She had a history of COPD, hypertension and polymyalgia rheumatica. A medication error involving methotrexate, used for autoimmune diseases, was discovered during her medical history review.
CASE PRESENTATION
The patient arrived with stable vital signs, including 94 % oxygen saturation and a respiratory rate of 20 breaths/min. She had been taking 2.5 mg of methotrexate daily for the past three weeks instead of the prescribed weekly dose of 15 mg. Other examinations revealed no alarming findings, except for a slightly elevated D-dimer level.
INTERPRETATION
Considering her medical history and exclusion of other differential diagnoses, methotrexate toxicity was suspected. The patient was admitted to the hospital and intravenous folinic acid was initiated as an antidote treatment. Five days later, the patient was discharged with an improvement in the shortness of breath. This case underscores the importance of effective communication in health care, particularly in complex cases like this, where understanding dosages and administration is crucial. Medical history, clinical examinations and medication reviews, often involving clinical pharmacists, are vital in the A&E to reveal medication errors.
Topics: Humans; Medication Errors; Female; Methotrexate; Aged; Dyspnea; Leucovorin; Antidotes; Antirheumatic Agents
PubMed: 38747669
DOI: 10.4045/tidsskr.23.0657 -
Palliative & Supportive Care Oct 2023
Topics: Humans; Sexuality; Death
PubMed: 36164993
DOI: 10.1017/S1478951522001262 -
Toxins Nov 2023In a few regions of the globe, deliberate botanical intoxication may induce significant rates of toxicity and fatality. The objective of this report was to describe... (Review)
Review
INTRODUCTION
In a few regions of the globe, deliberate botanical intoxication may induce significant rates of toxicity and fatality. The objective of this report was to describe plant self-intoxication using the experiences of the southeastern France poison control center (PCC) between 2002 and 2021.
RESULTS
During those 20 years, 262 deliberate plants poisonings were reported involving 35 various plants. In most of the cases, poisoning was caused by (n = 186, 71%), followed by the genus (4.2%), (3.8%), (1.9%), (1.2%), (1.9%), (1.5%), and (1.2%). Through the 262 plants poisonings, 19 patients among the 186 poisonings received Digifab as an antidote and 1 patient received physostigmine among the 11 Datura poisonings. Only four deaths were reported for this review, each involving .
DISCUSSION
The first involved species was (71% of all plants poisonings), then sp and . It is explained by this native local species' important repartition. Most patients must be admitted to an emergency department for adapted medical care; however, only 41 of them described severe poisonings symptoms. Even fewer needed an antidote, only 20 patients. There is no protocol for the use of a specific treatment, and it might be interesting to develop one for this purpose.
MATERIAL AND METHODS
This retrospective review was realized with files managed by the southeastern France PCC based in Marseille from 2002 to 2021. Our department covers the complete French Mediterranean coast, Corsica, and tropical islands (Reunion Island, Mayotte). For every patient, toxicity was evaluated using the Poison Severity Score (PSS).
Topics: Humans; Antidotes; France; Plant Poisoning; Poisons; Suicide, Attempted
PubMed: 38133175
DOI: 10.3390/toxins15120671 -
Bioorganic Chemistry Jul 2024Thrombosis leads to elevated mortality rates and substantial medical expenses worldwide. Human factor IXa (HFIXa) protease is pivotal in tissue factor (TF)-mediated...
Thrombosis leads to elevated mortality rates and substantial medical expenses worldwide. Human factor IXa (HFIXa) protease is pivotal in tissue factor (TF)-mediated thrombin generation, and represents a promising target for anticoagulant therapy. We herein isolated novel DNA aptamers that specifically bind to HFIXa through systematic evolution of ligands by exponential enrichment (SELEX) method. We identified two distinct aptamers, seq 5 and seq 11, which demonstrated high binding affinity to HFIXa (K = 74.07 ± 2.53 nM, and 4.93 ± 0.15 nM, respectively). Computer software was used for conformational simulation and kinetic analysis of DNA aptamers and HFIXa binding. These aptamers dose-dependently prolonged activated partial thromboplastin time (aPTT) in plasma. We further rationally optimized the aptamers by truncation and site-directed mutation, and generated the truncated forms (Seq 5-1t, Seq 11-1t) and truncated-mutated forms (Seq 5-2tm, Seq 11-2tm). They also showed good anticoagulant effects. The rationally and structurally designed antidotes (seq 5-2b and seq 11-2b) were competitively bound to the DNA aptamers and effectively reversed the anticoagulant effect. This strategy provides DNA aptamer drug-antidote pair with effective anticoagulation and rapid reversal, developing advanced therapies by safe, regulatable aptamer drug-antidote pair.
Topics: Aptamers, Nucleotide; Humans; Factor IXa; Antidotes; Dose-Response Relationship, Drug; Anticoagulants; Structure-Activity Relationship; Molecular Structure; SELEX Aptamer Technique
PubMed: 38776649
DOI: 10.1016/j.bioorg.2024.107463 -
Molecules (Basel, Switzerland) Dec 2023Vetiver root is widely used to produce essential oils in the aromatherapy industry. After the extraction of oil, the roots are disposed of as waste. The central...
Vetiver root is widely used to produce essential oils in the aromatherapy industry. After the extraction of oil, the roots are disposed of as waste. The central objective of this research was to explore the conversion of this waste into a resource using a circular economy framework. To generate biochar, vetiver roots were pyrolyzed at different temperatures (300, 500, and 700 °C) and residence times (30, 60, and 120 min). Analysis showed the root biochar generated at 500 °C and held for 60 min had the highest surface area of 308.15 m/g and a yield of 53.76%, in addition to other favorable characteristics. Comparatively, the surface area and the yield of shoot biochar were significantly lower compared to those of the roots. Repurposing the spent root biomass for environmental and agronomic benefits, our circular economy concept prevents the plant tissue from entering landfills or the waste stream.
Topics: Agriculture; Aromatherapy; Biomass; Industry; Charcoal
PubMed: 38202646
DOI: 10.3390/molecules29010063 -
Journal of Medical Toxicology :... Jul 2023The management of the poisoned patient often requires the utilization of uncommonly used pharmaceutical interventions. These interventions can be associated with... (Review)
Review
The management of the poisoned patient often requires the utilization of uncommonly used pharmaceutical interventions. These interventions can be associated with significant costs to both the patient and treating institution. Pharmaceutical supply shortages and issues with accessibility of antidotal therapies complicate the management of many toxic exposures. These challenges are an inherent property of the pharmaceutical purchasing infrastructure in the United States, which is a complicated network of public and private intra-institutional agreements. The cost and availability of any given therapy is dependent on the individual contracting agreements between the treating institution, payer, pharmacy benefit manager, manufacturer or wholesaler, and in some cases a specialty pharmacy. Small or remote hospitals may experience greater challenges related to insufficient patient volume to achieve predicable prescribing patterns of rare and expensive medications, necessitating consignment purchasing arrangements. Although pharmaceutical costs are the focus of recent legislative attention, these reforms are not expected to significantly alter the cost or availability of antidotal therapies.
Topics: Humans; United States; Antidotes; Drug Costs; Pharmacies; Pharmacy; Pharmaceutical Preparations
PubMed: 37249803
DOI: 10.1007/s13181-023-00943-5 -
Drug Metabolism and Disposition: the... Oct 2023In the early '70s, Dr B. B. Brodie, Head of the LCP, NHI, NIH, initiated a program to elucidate the mechanism of hepatic necrosis induced in rats by bromobenzene. These...
In the early '70s, Dr B. B. Brodie, Head of the LCP, NHI, NIH, initiated a program to elucidate the mechanism of hepatic necrosis induced in rats by bromobenzene. These studies showed a crucial role for its 3,4-epoxide intermediate, known in part, to collapse to 4-bromophenol. To examine a possible contribution of this phenol to tissue toxicity, some rats were co-administered a high dose of acetaminophen to suppress phenolic clearance by glucuronidation and sulfation. Subsequent examination of liver slices showed that the acetaminophen-only control rats had extensive centrilobular liver necrosis. This article is a personal reminiscence of the events that led up to this accidental observation, how it happened, and the subsequent resolution of the underlying mechanism, including the covalent binding of NAPQI to liver protein as the initial "hit", the glutathione protective threshold, the antidotal activity of cysteine, and the existence of the "therapeutic window" for antidotal therapy. Collectively, these studies formed the basis for antidotal therapy of acetaminophen overdose patients, Not applicable.
PubMed: 37793785
DOI: 10.1124/dmd.123.001278