Efonidipine-Induced Exanthematic Drug Eruption and Literature Review.

We report the case of an elderly woman who developed exanthematic drug eruption after administration of efonidipine. An 84-year-old woman presented to emergency department with complaints of generalized itching and erythema since 4 days. She was on human-soluble insulin since 11 years. In view of her hypertension and left anterior descending artery stenosis, she was initiated on aspirin, clopidogrel, atorvastatin, pantoprazole, nebivolol, aldactone, and efonidipine a week ago. Her presenting complaints were initially managed with parenteral pheniramine maleate and hydrocortisone. She was admitted, and all her medications except antiplatelets and insulin were discontinued. She was prescribed topical beclomethasone and oral antihistamines for better control of her symptoms. To confirm the drug precipitating the reaction, she was rechallenged with efonidipine, 20 mg once daily on the third day of admission. She developed itching 8 hours after administering the medication, and efonidipine was stopped and nebivolol 5 mg once daily was restarted for hypertension. She did not develop any adverse event when the remaining medications were reinitiated. World Health Organization-Uppsala Monitoring Centre causality assessment criteria indicated a "certain" association. To the best of the knowledge of the authors, this is one among the first reported cases of efonidipine-induced exanthematic drug eruption.

Solid lipid nanoparticles affect microbial colonization and enzymatic activity throughout the decomposition of alder leaves in freshwater microcosms.

Solid lipid nanoparticles (SLNs) are used as carriers for drug delivery, and are high biocompatible and designed to endure in the host organism. Despite its current industrial production is low, many of these substances are available on the market, and much more are in the production pipeline. As a result, many of them will end in aquatic systems raising the question whether they can pose a risk to aquatic biota and the associated ecological processes. Microbial decomposers of plant litter, play a key role in forested streams being responsible for the energy flow between terrestrial and aquatic environments. Here, we investigated the effects of SLNs on alder leaf litter decomposition by aquatic microbes. Alder leaves were immersed in a stream of Northeast Portugal to allow microbial colonization before being exposed in microcosms of two types of SLNs at two concentrations for 42 days. Results showed that rates of leaf decomposition decreased with exposure to SLNs. Bacterial biomass was not inhibited by SLNs, and cultivable fungi densities remained constant (SLN-A) or increased (SLN-C) compared with control microcosms. The type and concentration of SLNs influenced differently the leaf colonization by fungi as well as fungal sporulation rate. These effects were accompanied by changes in the community extraenzymatic profile: the activities of alkaline phosphatase, acidic phosphatase, Naphthol-AS-BI-phosphohydrolase (P cycle) and lipases increased in the SLNs microcosms. This study provided the first evidence of the adverse effects of the release of SLNs to streams on leaf litter decomposition. Those effects seem to depend on the composition and concentration of SLNs, as well on the microbial target group, or enzyme. Thus, prior to massive industrial production of these nanomaterials, some measures should be taken to avoid environmental impact affecting the microbial communities responsible for detritus decomposition.

Assessment of coronary ischaemia by myocardial perfusion dipyridamole stress technetium-99 m tetrofosmin, single-photon emission computed tomography, and coronary angiography in children with Kawasaki disease: pre- and post-coronary bypass grafting.

BACKGROUND: Coronary artery lesions in Kawasaki disease invasively assessed by coronary angiography. Evaluation of myocardial perfusion by single-photon emission computed tomography may identify the haemodynamic significance of coronary lesions. OBJECTIVE: To evaluate diagnostic accuracy of dipyridamole stress technetium-99 m tetrofosmin, single-photon emission computed tomography as a possible alternative to invasive coronary angiography for detection and follow-up of myocardial ischaemia in patients with Kawasaki disease, and pre- and post-coronary bypass grafting. PATIENTS AND METHODS: Coronary angiography and single-photon emission computed tomography were performed on 21 patients who were classified into three groups - group I (stenosis), group II (giant aneurysms), and group III (small aneurysms). Of the 21 patients, 16 (groups I and II) patients with myocardial perfusion defects, who underwent coronary bypass grafting, were followed up with single-photon emission computed tomography. RESULT: In group I, all patients had significant coronary stenosis and 100% of them had perfusion defects in the anterior and septal walls. In group II, all patients had giant aneurysms and 83% of them had inferior and inferolateral perfusion defects. In group III, all patients had small aneurysms and 100% of them had normal perfusion. Pre-coronary bypass grafting myocardial ischaemic defects disappeared in all patients after surgery. Sensitivity, specificity, and accuracy of single-photon emission computed tomography were 94, 100, and 95%, respectively. CONCLUSION: Technetium-99 m tetrofosmin single-photon emission computed tomography can be applied as an accurate non-invasive diagnostic technique for detecting myocardial perfusion defects with coronary artery lesions, and to show improved or even normalised perfusion of the myocardium in patients after surgical revascularisation.

Volatile organic compounds emission control in industrial pollution source using plasma technology coupled with F-TiO2/γ-Al2O3.

Volatile organic compounds' (VOCs) effluents, which come from many industries, are triggering serious environmental problems. As an emerging technology, non-thermal plasma (NTP) technology is a potential technology for VOCs emission control. NTP coupled with F-TiO2/γ-Al2O3 is used for toluene removal from a gaseous influent at normal temperature and atmospheric pressure. NTP is generated by dielectric barrier discharge, and F-TiO2/γ-Al2O3 can be prepared by sol-gel method in the laboratory. In the experiment, the different packed materials were packed into the plasma reactor, including γ-Al2O3, TiO2/γ-Al2O3 and F-TiO2/γ-Al2O3. Through a series of characterization methods such as X-ray diffraction, scanning electronic microscopy and Brunner-Emmet-Teller measurements, the results show that the particle size distribution of F-TiO2 is relatively smaller than that of TiO2, and the pore distribution of F-TiO2 is more uniformly distributed than that of TiO2. The relationships among toluene removal efficiency, reactor input energy density, and the equivalent capacitances of air gap and dielectric barrier layer were investigated. The results show that the synergistic technology NTP with F-TiO2/γ-Al2O3 resulted in greater enhancement of toluene removal efficiency and energy efficiency. Especially, when packing with F-TiO2/γ-Al2O3 in NTP reactor, toluene removal efficiency reaches 99% and higher. Based on the data analysis of Fourier Transform Infrared Spectroscopy, the experimental results showed that NTP reactor packed with F-TiO2/γ-Al2O3 resulted in a better inhibition for by-products formation effectively in the gas exhaust.

[On necessity to modify biochemical methods for detecting organophosphorus componds in chemical weapons extinction objects (review of literature)].

The article covers problems of biochemical methods assessing organophosphorus toxic compounds in objects of chemical weapons extinction. The authors present results of works developing new, more specific and selective biochemical methods.

Are we prepped for preexposure prophylaxis (PrEP)? Provider opinions on the real-world use of PrEP in the United States and Canada.

BACKGROUND: Preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine (Truvada) has demonstrated efficacy in placebo-controlled clinical trials involving men who have sex with men, high-risk heterosexuals, serodiscordant couples, and intravenous drug users. To assist in the real-world provision of PrEP, the Centers for Disease Control and Prevention (CDC) has released guidance documents for PrEP use. METHODS: Adult infectious disease physicians were surveyed about their opinions and current practices of PrEP through the Emerging Infections Network (EIN). Geographic information systems analysis was used to map out provider responses across the United States. RESULTS: Of 1175 EIN members across the country, 573 (48.8%) responded to the survey. A majority of clinicians supported PrEP but only 9% had actually provided it. Despite CDC guidance, PrEP practices were variable and clinicians reported many barriers to its real-world provision. CONCLUSIONS: The majority of adult infectious disease physicians across the United States and Canada support PrEP but have vast differences of opinion and practice, despite the existence of CDC guidance documents. The success of real-world PrEP will likely require multifaceted programs addressing barriers to its provision and will be assisted with the development of comprehensive guidelines for real-world PrEP.

Role of oral pre-exposure prophylaxis (PrEP) in current and future HIV prevention strategies.

Treatment as prevention is expected to have a major role in reducing HIV incidence, but other prevention interventions will also be required to bring the epidemic under control, particularly among key populations. One or more forms of pre-exposure prophylaxis (PrEP) will likely play a critical role. Oral PrEP with emtricitabine-tenofovir (Truvada®) is currently available in the US and some other countries, but uptake has been slow. We review the concerns that have contributed to this slow uptake and discuss current and future research in this critical area of HIV prevention research.

Mitoquinone mesylate as post-exposure prophylaxis against SARS-CoV-2 infection in humans: an exploratory single center pragmatic open label non-randomized pilot clinical trial with matched controls.

BACKGROUND: An ongoing important need exists to rapidly develop novel therapeutics for COVID-19 that will retain antiviral efficacy in the setting of rapidly evolving SARS-CoV-2 variants and potential future development of resistance of SARS-COV-2 to remdesivir and protease inhibitors. To date, there is no FDA-approved treatment for post-exposure prophylaxis against SAR-CoV-2. We have shown that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has antiviral activity against SARS-CoV-2 in vitro and in SARS-CoV-2 infected K18-hACE2 mice. METHODS: In this exploratory, pragmatic open label clinical trial (ClinicalTrials.gov identifier NCT05381454), we studied whether Mito-MES is an effective post-exposure prophylaxis treatment in people who had high-grade unmasked exposures to SARS-CoV-2 within 5 days prior to study entry. Participants were enrolled in real-world setting in Los Angeles, United States between May 1 and December 1, 2022 and were assigned to either mito-MES 20 mg daily for 14 days (n = 40) or no mito-MES (controls) (n = 40). The primary endpoint was development of SARS-CoV-2 infection based on 4 COVID-19 diagnostic tests [rapid antigen tests (RATs) or PCR] performed during the study period (14 days post exposure). FINDINGS: Out of 40 (23 females; 57.5%) study participants who took Mito-MES, 12 (30%) developed SARS-CoV-2 infection compared to 30 of the 40 controls (75%) (difference -45.0%, 95% confidence intervals (CI): -64.5%, -25.5%). Out of 40 (19 females; 47.5%) study participants in the control group, 30 (75.0%) had at least one positive COVID-19 diagnostic test and 23 (57.5%) were symptomatic. With regards to key secondary outcomes, among symptomatic SARS-CoV-2 infections, the median duration of viral symptoms was lower in the Mito-MES group (median 3.0, 95% CI 2.75, 3.25) compared to the control group (median 5.0, 95% CI 4.0, 7.0). None of the study participants was hospitalized or required oxygen therapy. Mito-MES was well tolerated and no serious side effect was reported in any study participant. INTERPRETATION: This work describes antiviral activity of mito-MES in humans. Mito-MES was well tolerated in our study population and attenuated transmission of SARS-CoV-2 infection. Given established safety of Mito-MES in humans, our results suggest that randomized control clinical trials of Mito-MES as post-exposure prophylaxis against SARS-CoV-2 infection are warranted. FUNDING: This work was supported in part by National Institutes of Health grant R01AG059501 (TK), National Institutes of Health grant R01AG059502 04S1 (TK), NIH/National Center for Advancing Translational Sciences (NCATS) UCLA CTSI Grant Number UL1TR001881 and California HIV/AIDS Research Program grant OS17-LA-002 (TK).

High acceptability of HIV pre-exposure prophylaxis but challenges in adherence and use: qualitative insights from a phase I trial of intermittent and daily PrEP in at-risk populations in Kenya.

This paper used qualitative methods to explore experiences of men who have sex with men and female sex workers in Nairobi and Mtwapa, Kenya, who used oral pre-exposure prophylaxis (PrEP) for HIV prevention as part of a four-month trial of safety, acceptability and adherence. Fifty-one of 72 volunteers who took part in a randomized, placebo-controlled, blinded trial that compared daily and intermittent dosage of PrEP underwent qualitative assessments after completing the trial. Analyses identified three themes: (i) acceptability of PrEP was high, i.e. side effects were experienced early in the study but diminished over time, however characteristics of pills could improve comfort and use; (ii) social impacts such as stigma, rumors, and relationship difficulties due to being perceived as HIV positive were prevalent; (iii) adherence was challenged by complexities of daily life, in particular post-coital dosing adherence suffered from alcohol use around time of sex, mobile populations, and transactional sex work. These themes resonated across dosing regimens and gender, and while most participants favored the intermittent dosing schedule, those in the intermittent group noted particular challenges in adhering to the post-coital dose. Culturally appropriate and consistent counseling addressing these issues may be critical for PrEP effectiveness.

[The non-hormonal treatment of metastatic prostate cancer]. / Le traitement non hormonal de la maladie métastatique du cancer de la prostate.

AIM: To describe drugs used in the non-hormonal treatment of metastatic prostate cancer. MATERIAL: Bibliographical search was performed from the database Medline (National Library of Medicine, PubMed) and websites of the HAS and the ANSM. The search was focused on the characteristics, the mode of action, the efficiency and the side effects of the various drugs concerned. RESULTS: The metabolic radiotherapy although under-used for this indication, kept a place at the beginning of the disease. Radium-223 chloride seems to have to occupy an important place in the coming years. The chemotherapy, the only recourse until very recently in the castration-resistant prostate cancer, must redefine its place partially. The denosumab provide an interesting alternative to bisphosphonates. CONCLUSION: The non-hormonal treatment of the metastatic disease of the prostate cancer is changing rapidly with the emergence of new molecules. Urologist must know perfectly these new drugs.

Betulinic acid protects against cardiotoxicity of the organophosphorus pesticide chlorpyrifos by suppressing oxidative stress, inflammation, and apoptosis in rats.

The widespread application of organophosphorus (OP) pesticides can affect the environment as well as the animal and human health. Chlorpyrifos (CPF) is a broad-spectrum OP pesticide used in agriculture and can cause several toxic effects in which oxidative stresses and inflammation play a key role. This study aimed to evaluate the protective activity of betulinic acid (BA), an antioxidant and anti-inflammatory pentacyclic triterpene, against CPF cardiotoxicity in rats. The rats were divided into four groups. CPF (10 mg/kg) and BA (25 mg/kg) were orally administered for 28 days, and blood and heart samples were collected. CPF-administered rats showed an increase in serum cardiac troponin I (cTnI), creatine kinase (CK)-MB, and lactate dehydrogenase (LDH), accompanied with multiple myocardial tissue alterations. Lipid peroxidation (LPO), nitric oxide (NO), nuclear factor-kappaB (NF-κB), interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α were increased, and antioxidant were decrease in CPF-administered rats. BA ameliorated cardiac function markers and tissue injury, decreased LPO, NO, NF-κB, and proinflammatory cytokines, and increased antioxidants. In addition, BA decreased proapoptosis markers, and increased B-cell lymphoma (Bcl)-2, IL-10, Nrf2, and HO-1 in the heart of CPF-treated rats. In conclusion, BA protected against cardiotoxicity in CPF-administered rats by mitigating oxidative stress, inflammation, and apoptosis, and enhanced Nrf2 and antioxidants.

Therapeutic strategies for bone metastases and their clinical sequelae in prostate cancer.

OPINION STATEMENT: Skeletal metastases threaten quality of life, functionality, and longevity in patients with metastatic castration-resistant prostate cancer (mCRPC). Therapeutic strategies for bone metastases in prostate cancer can palliate pain, delay/prevent skeletal complications, and prolong survival. Pharmacologic agents representing several drug classes have demonstrated the ability to achieve these treatment goals in men with mCRPC. Skeletal-related events such as fracture and the need for radiation can be delayed using drugs that target the osteoclast/osteoblast pathway. Cancer-related bone pain can be palliated using beta-emitting bone-seeking radiopharmaceuticals such as samarium-153 EDTMP and strontium-89. Also, prospective randomized studies have demonstrated that cytotoxic chemotherapy can palliate bone pain. For the first time, bone-directed therapy has been shown to prolong survival using the novel alpha-emitting radiopharmaceutical radium-223. Given these multifold clinical benefits, treatments targeting bone metabolism, tumor-bone stromal interactions, and bone metastases themselves are now central elements of routine clinical care. Decisions about which agents, alone or in combination, will best serve the patient's and clinician's clinical goals is contingent on the treatment history to date, present disease manifestations, and symptomatology. Clinical trials exploring novel agents such as those targeting c-Met and Src are under way, using endpoints that directly address how patients feel, function, and survive.

DIPHOS® nail for proximal humeral fractures: our experience with more than 190 procedures and surgical tips.

AIM: evaluate the outcome of proximal  humeral nailing over 5 years follow-up, focusing  on possible complications. Secondary endpoint is the description and analysis of some technical notes to simplify surgical procedure. MATERIALS AND METHODS: the cohort is composed by 194 fractures fixed with short nail. Neer Classification was used to assess the type of fracture; Deltoid Tuberosity Index (DTI) was applied to verify local bone quality. Follow-up with X-rays and orthopaedic evaluation was conducted on every operated subject. RESULTS: mean follow up of the study was 25.4 months. We registered an average CMS score of 84.66 points for 2-parts fractures, 79.05 points for 3-part fractures and 68.62 points for 4-parts fractures. We obtained radiographical healing in 95.9% of patients (186/194) after 2.7 months on average. We recorded "very good" / "good" results in 90.3% of 2-parts fractures, 88.5% of 3-parts fractures and 46.2% of 4-part fractures. Overall complication rate was 10.3% (20/194 nails).  Second surgery was performed in 8.2% (16/194) of cases. CONCLUSION: intramedullary nailing is an effective treatment for 2 and 3-part fractures with relatively low incidence of complications, small surgical accesses and short surgical time. Future researches are necessary to analyze the results related to nailing in 4-fragment fractures, still uncertain and influenced by multiple factors. The presence of the intramedullary nail reduces the lever arm of the screws making the osteosynthesis more reliable. Modern nails guarantee angular stability for proximal cancellous screws and allows 1 or 2 screws at calcar level to get a valid medial support.

Urinary DAP metabolite levels in Thai farmers and their families and exposure to pesticides from agricultural pesticide spraying.

INTRODUCTION: We conducted a biomarker study to characterise exposure to pesticides among farmers and their families in Thailand to assess the relative importance of the dermal exposure route and to identify important factors that determine exposure levels within farmers' families. METHODS: Sixteen farmers' families (eight vegetable and eight fruit farmers) participated in the study. Three morning spot urine samples were collected during a pesticide spraying week. Spot samples were grouped by individual and analysed for dialkylphosphate (DAP) metabolites and creatinine. Additional information on exposure and lifestyle was collected by means of questionnaires. Dermal exposure was assessed using a semi-quantitative observational method (DREAM). RESULTS: Urinary DAP levels varied 20-fold between farmers, with average (geometric mean) levels of 51.1 µg/g for vegetable and 122.2 µg/g for fruit farmers. A moderate correlation (r(s)∼0.45) was found between log(e)-transformed DREAM scores and DAP levels. Farmers' urinary metabolite levels were not correlated with those of their spouses (r(s)∼-0.30) or children (r(s)∼-0.00) collected on the same days. Detectable spouses' DAP levels were on average (geometric mean) 13.0 µg/g and those of children 7.6 µg/g. DISCUSSION: Farmers in Thailand as well as their families are exposed to pesticides in the spraying season and dermal exposure is an important route. The main route of exposure for farmers' families seems to be through transfer from the farmer to family members or contamination of the home environment, rather than family members helping or playing on the farm. Showering or washing immediately after pesticide spraying greatly reduces the potential exposure of family members to pesticide residues.

Effects of enfonidipine hydrochloride in dogs with experimental supraventricular tachyarrhythmia.

It is required not to increase the ventricular rate and to preserve the ventricular systolic function in treating supraventricular tachyarrhythmia (SVTA). The objective of this study is to investigate whether or not Efonidipine hydrochloride (EH), a T and L dual type Ca(2+) channel blocker, suppresses the increasing ventricular rate without reducing the ventricular systolic function using canine SVTA models by rapid atrial pacing (RAP) method. Clinically healthy fourteen beagles were used. The 14 dogs were randomly assigned to the EH-administered group (EH group, n=7) and non-EH-administered group (control group, n=7). The EH group was orally-administered EH at 5 mg/kg SID during RAP. On the other hand, the control group was applied RAP without oral administration of EH. Duration of RAP was for 3 weeks for both groups. The ventricular rate for the EH group was significantly lower than that for the control group. The left ventricular- fractional shortening for the control group declined significantly compared to baseline. Those for the EH group did not show any changes over time and were significantly higher than the control group. The ratio between pre-ejection period and ejection for the EH group were significantly lower than those of the control group. In conclusion, the study demonstrated that EH suppresses the increasing ventricular rate without reducing the ventricular systolic function in canine SVTA model. Therefore, EH is expected to become a new treatment for canine SVTA.