Exploring research gaps and trends in the management of acute phosphide poisoning: a systematic 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 (Zn3P2) poisoning (p-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 p-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.

Pharmacokinetics of single-dose rivaroxaban under fed state in obese vs. non-obese subjects: An open-label controlled clinical trial (RIVOBESE-PK).

The evidence of rivaroxaban's pharmacokinetics in obese compared with non-obese populations remains inconclusive. We aimed to compare the pharmacokinetic profile of rivaroxaban between obese and non-obese populations under fed state. Participants who met the study's eligibility criteria were assigned into one of two groups: obese (body mass index ≥35 kg/m2) or non-obese (body mass index 18.5-24.9 kg/m2). A single dose of rivaroxaban 20 mg was orally administered to each participant. Nine blood samples over 48 h, and multiple urine samples over 18 h were collected and analyzed for rivaroxaban concentration using ultra-performance liquid chromatography coupled with tandem mass detector. Pharmacokinetic parameters were determined using WinNonlin software. Thirty-six participants were recruited into the study. No significant changes were observed between obese and non-obese participants in peak plasma concentration, time to reach peak plasma concentration, area under the plasma concentration-time curve over 48 h or to infinity, elimination rate constant, half-life, apparent volume of distribution, apparent clearance, and fraction of drug excreted unchanged in urine over 18 h. Rivaroxaban's exposure was similar between the obese and non-obese subjects, and there were no significant differences in other pharmacokinetic parameters between the two groups. These results suggest that dose adjustment for rivaroxaban is probably unwarranted in the obese population.

The possible thyroid disruptive effect of di-(2-ethyl hexyl) phthalate and the potential protective role of selenium and curcumin nanoparticles: a toxicological and histological study.

Di-(2-ethylhexyl) phthalate (DEHP) is one of the ubiquitous pollutants worldwide. This study aimed to clarify the potential thyroid disrupting effect of DEHP and explore the probable ameliorative effects of selenium nanoparticles (Se-NPs) and curcumin nanoparticles (CUR-NPs). Forty-two male albino rats were divided into seven groups (n = 6): Group I (negative control); group (II) orally received DEHP (500 mg/kg BW, dissolved in corn oil); Group (III) orally received Se-NPs (.2 mg/kg BW) in combination with DEHP; Group (IV) orally received CUR-NPs (15 mg/kg BW) alongside with DEHP; Group V (corn oil); Group VI (Se-NPs) and Group VII (CUR-NPs). The duration of the experiment was 30 days. DEHP administration significantly decreased serum free T4 and significantly increased serum free T3 as compared to control group, whereas thyroid-stimulating hormone showed no significant change. DEHP disrupted redox status leading to accumulation of malondialdehyde and depletion of reduced glutathione. Histologically, the effect of DEHP on thyroid follicles was confirmed by light and electron microscopic examination and morphometric analysis. Se-NPs slightly improved thyroid parameters as well as redox status. CUR-NPS reinstated the values of all studied thyroid parameters to nearly control levels. This research provides Se-NPs and CUR-NPs as novel protective agents against DEHP-thyroid disrupting effects.

In vitro release, rheological, and stability studies of mefenamic acid coprecipitates in topical formulations.

A suitable topical formulation of mefenamic acid was developed in order to eliminate the gastrointestinal disorders associated with its oral administration. Drug coprecipitates prepared with different polymers at various drug-to-polymer ratios improved drug solubility and dissolution compared to pure drug and physical mixtures. PVP polymers (ratio 1:4) produced the best results. Aqueous ionic cream, ointments of absorption and water soluble bases and gels of methylcellulose, carboxymethylcellulose sodium, HPMC, Carbopol® 934 and 940, and Pluronic® F127 bases containing 1-10% drug as coprecipitates of PVP polymers (1:4) were prepared. The highest drug release was achieved at 1% drug concentration from water soluble base and methylcellulose among cream/ointment and gel bases, respectively. Gels, in general yielded better release than creams/ointments. All tested medicated creams/ointments exhibited plastic flow while all gels conformed to pseudoplasticity. Most of them showed thixotropy, a desired property of topical preparations. Stability studies revealed that HPMC and methylcellulose had the smallest changes in drug content, viscosity, and pH among the formulations. Considering drug release, rheological properties, and stability, methylcellulose gel containing 1% drug as coprecipitates of PVP K90 was the best among the studied formulations, was promising for improving bioavailability of mefenamic acid and can be used in future studies.

Intratracheal Administration of Chloroquine-Loaded Niosomes Minimize Systemic Drug Exposure.

Pulmonary administration provides a useful alternative to oral and invasive routes of administration while enhancing and prolonging the accumulation of drugs into the lungs and reducing systemic drug exposure. In this study, chloroquine, as a model drug, was loaded into niosomes for potential pulmonary administration either via dry powder inhalation or intratracheally. Chloroquine-loaded niosomes have been prepared and extensively characterized. Furthermore, drug-loaded niosomes were lyophilized and their flowing properties were evaluated by measuring the angle of repose, Carr's index, and Hausner ratio. The developed niosomes demonstrated a nanosized (100-150 nm) spherical morphology and chloroquine entrapment efficiency of ca. 24.5%. The FT-IR results indicated the incorporation of chloroquine into the niosomes, whereas in vitro release studies demonstrated an extended-release profile of the drug-loaded niosomes compared to the free drug. Lyophilized niosomes exhibited poor flowability that was not sufficiently improved after the addition of lactose or when cryoprotectants were exploited throughout the lyophilization process. In vivo, intratracheal administration of chloroquine-loaded niosomes in rats resulted in a drug concentration in the blood that was 10-fold lower than the oral administration of the free drug. Biomarkers of kidney and liver functions (i.e., creatinine, urea, AST, and ALT) following pulmonary administration of the drug-loaded nanoparticles were of similar levels to those of the control untreated animals. Hence, the use of a dry powder inhaler for administration of lyophilized niosomes is not recommended, whereas intratracheal administration might provide a promising strategy for pulmonary administration of niosomal dispersions while minimizing systemic drug exposure and adverse reactions.

Evaluation of possible molecular toxicity induced by occupational exposure to lead and concomitant effect of smoking.

One of the most toxic heavy metals in the environment nowadays is lead (Pb). Even though exposure to lead has been reduced in some developed countries, individuals working in certain occupations are still exposed to lead at dangerous levels. Occupational exposure is of great concern and is also the main cause of lead poisoning. Although experts in various fields have been investigating the toxic effects of lead and its compounds for many years now, the association between chronic lead exposure and geno-toxicity is still an interesting point of research. The study aims to evaluate the possible DNA damage and the oxidative stress status induced by occupational exposure to lead and the role of concomitant smoking. The study was conducted on 60 subjects divided into two groups: an exposed group (40 male workers exposed to lead in their workplaces). This group was further divided into two subgroups; 20 workers were cigarette smokers and the other 20 workers were non-smokers. The other control group consists of 20 healthy males, not exposed to lead and matched by age to the exposed group (10 were smokers and the rest were non-smokers). Venous blood samples were collected from each participant for the determination of the following: blood lead level (BLL), plasma malondialdehyde (MDA) levels, and DNA damage using agarose gel electrophoresis. The exposed workers had significantly higher levels of lead and MDA, as well as a high frequency of DNA fragmentation. Smoking workers showed a greater frequency of DNA fragmentation than non-smokers. A significant relation was revealed between the BLL, as well as the MDA level, and the degree of DNA fragmentation among the lead-exposed workers. The study has shown additional evidence proving the association between Pb exposure and oxidative stress. The results further reinforced the role of cigarette smoking in augmenting such oxidative damage in the Pb-exposed population. However, further studies are recommended to evaluate the effect of cigarette smoking on Pb-exposed workers.

Development of biodegradable in situ implant and microparticle injectable formulations for sustained delivery of haloperidol.

The objective of this study is to formulate injectable, biodegradable sustained release in situ implant (ISI), and in situ microparticle (ISM) formulations of haloperidol. Factors affecting the in vitro drug release, pharmacokinetics, and stability of the formulations were investigated. The concentration of the polymer, poly(lactide-co-glycolide) acid (PLGA), and the type of solvents showed a pronounced effect on the in vitro drug release from the ISI and ISM formulations. The ISM formulation [20% PLGA in N-methyl-2-pyrrolidone (NMP)-peanut oil, 1:4] showed reduced maximum plasma concentration (60 versus 44 ng/mL) and longer release (30 days, plasma concentration of 8 ng/mL versus 20 days, plasma concentration of 6 ng/mL) compared with the ISI formulation (20% PLGA in NMP) after intramuscular injection in rats. The delivery of haloperidol can be extended further by changing the concentration, molecular weight, and lactide-to-glycolide ratio of the PLGA. These formulations can be easily administered by both intramuscular and subcutaneous injections. The shelf lives of both systems were found to be 2 years when stored at 4°C. Haloperidol can be formulated as an injectable ISI or ISM systems suitable for 1 month or longer release.