Inhibition of soluble epoxide hydrolase by natural isothiocyanates.

GOAL: The long-term goal of our research is to develop safe and effective soluble epoxide hydrolase (sEH) inhibitors. The objective of this study is to evaluate the potency and selectivity of six natural isothiocyanates (ITCs) as sEH inhibitors. METHODS: Molecular docking was used to model likely interactions between the ligands and receptors. The sEH inhibitory activity was tested using a validated fluorescence-based assay and PHOME as a substrate. To evaluate their selectivity as sEH inhibitors, the inhibitory potential of the ITCs was determined on microsomal epoxide hydrolase (mEH) and cytochrome P450 (CYP) enzymes in human liver microsomes. Probe substrates such as styrene oxide (mEH substrate) and established substrates for CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 were used in this study. The metabolites of these substrates were analyzed using validated LC-MS/MS and HPLC-UV assays. RESULTS: Molecular Docking revealed significant differences in binding site preference among the ITCs in silico and pointed to important interactions between the ligands and the catalytic residues of the sEH enzyme. In vitro, the ITCs showed varying degrees of sEH inhibition, but sulforaphane (SFN) and phenyl isothiocyanate (PITC) were the most potent inhibitors with IC50 values of 3.65 and 7.5 µM, respectively. mEH was not significantly inhibited by any of the ITCs. Erucin and iberin were the only ITCs that did not inhibit the activity of any of the tested CYP enzymes. CONCLUSION: Our results demonstrate that natural ITCs have the potential to offer safe, selective, and potent sEH inhibition.

The effects of genetic polymorphism on toxicity and pharmacokinetics of methotrexate in Egyptian adult patients with leukaemia or lymphoma.

Polymorphisms in genes coding folate-metabolising enzymes might alter the pharmacokinetics and sensitivity for methotrexate "MTX".The aim of the study aimed to investigate the influence of MTHFR C677T, DHFR19 Ins/del, GGH -401 C > T, and MTR A2756G polymorphisms on MTX toxicity and pharmacokinetics in Egyptian patients with Acute lymphoblastic leukaemia (ALL) or Non-Hodgkin lymphoma (NHL).Fifty adult Egyptian patients with ALL and NHL, treated with high dose MTX, were prospectively enrolled in the study. Clinical and biochemical data was collected objectively from medical records after each cycle of MTX. Plasma concentrations of MTX were measured after 72 h of initiation of infusion. Genotyping was done with a PCR-ARMS and PCR-RFLP assays.The MTHFR C677T T variants significantly increased the risk of leukopoenia, whereas the genotype MTHFR 677 C > T TT significantly associated with lymphocytopenia, thrombocytopenia, and anaemia. The genotype GGH-401 TT was significantly correlated with anaemia. Plasma MTX level was significantly higher in patients with MTR A2756G G variants.MTHFR polymorphism played the main role in MTX toxicities. The pharmacokinetics of MTX was affected by MTR polymorphism. GGH mutation was mainly concerned with anaemia. Pharmacogenetic testing are recommended to optimise MTX therapy.

Linezolid-associated serotonin toxicity: a systematic review.

PURPOSE: This systematic review aims to evaluate the existing evidence associating linezolid to serotonin toxicity when used as monotherapy or when co-administered with other serotonergic agents. METHODS: A systematic literature search using PubMed (till March 2023), IDWeek meetings (2003-2023), the European Congress of Clinical Microbiology and Infectious Disease Annual Meetings (2001-2023), and the American College of Clinical Pharmacy (1999-2023) identified studies and abstracts related to linezolid and serotonin toxicity. RESULTS: A total of 84 studies were included. The data collected in retrospective/observational studies compared the incidence of serotonin toxicity with linezolid monotherapy at 0.0050% and linezolid combination therapy at 0.0134%. All cases which discontinued linezolid and serotonergic agent/s at signs and symptoms of toxicity found symptom resolution; 75% of cases reported serotonin toxicity resolution within 24-48 h after discontinuation. CONCLUSION: Linezolid therapy when optimal should not be deferred due to the risk of serotonin syndrome. The data collected reveals a low prevalence of serotonin toxicity in both linezolid monotherapy and linezolid concurrent with other serotonergic agents.

Changes in dietary habits during Covid-19 lockdown in Egypt: the Egyptian COVIDiet study.

PURPOSE: COVID-19 lockdown changed social habits and lifestyle, including dietary habits, of people worldwide. However, limited information is available about these changes in Egypt. This cross-sectional study investigates the effects of COVID-19 lockdown on dietary habits among the Egyptian populations. METHODS: An online questionnaire, based on sociodemographic data and dietary adherence in accordance with the validated PREDIMED MedDiet Adherence Screener (MEDAS), was used all over the Egyptian governorates. The dietary changes were statistically evaluated for significance in relation to age, gender, body mass index (BMI), education level and governorates. RESULTS: A total of 1010 participants (76% aged below 36 years, 77% female, 22% obese, and 62% university-level education) answered the questionnaire. Respondents ≤ 20 years had a significant increase in weight and consumption of carbonated beverages, commercial pastries, fried and fast food. Egyptians > 50 years old had a significant decrease in physical activity. Underweight people (less than 3% of participants) increased their fast food intake with a prominent rise in weight. However, obese people increased cooking frequency and increased eating times with a decrease in physical activity. Male participants reported increased intake of carbonated beverages and fast food, while female participants increased the intake of homemade pastries with a significant decrease in physical activity. Approximately 50% of participants with postgraduate education reported decreased intake of fast food and carbonated beverages as well as decreased body weight. Residents of Cairo showed a significant increase in vegetable intake, and fried food intake with a decrease in seafood consumption. Participants from the Delta region had a significant increase in pastries intake. CONCLUSION: The findings of this study explored the need for increasing awareness about healthy lifestyle in future lockdown periods.

LC-MS/MS bioanalytical method for the quantitative analysis of nifedipine, bisoprolol, and captopril in human plasma: Application to pharmacokinetic studies.

In this study, the development and validation of an accurate and highly sensitive LC-MS/MS method were performed for the estimation of nifedipine, bisoprolol and captopril in real human plasma. Liquid-liquid extraction using tert-butyl methyl ether was efficiently applied for extraction of the analytes from plasma samples. The chromatographic separation was carried out using an isocratic elution mode on the X-terra MS C18 column (4.6 × 50 mm, 3.5 µm). The mobile phase consisted of methanol-0.1% formic acid (95:5, v/v) for determination of nifedipine and bisoprolol and acetonitrile-0.1% formic acid (70:30, v/v) for determination of captopril with a flow rate of 0.5 ml/min. Acceptable results regarding the different validation characteristics of the analytes were obtained in accordance with US Food and Drug Administration recommendations for bioanalytical methods. The developed approach was linear over concentration ranges of 0.5-130.0, 50.0-4,500.0 and 0.3-30.0 ng/ml for nifedipine, captopril and bisoprolol, respectively. The method revealed a sufficient lower limit of quantification in the range of 0.3-50.0 ng/ml, as well as high recovery percentages, indicating high bioanalytical applicability. The proposed method was efficiently applied to a pharmacokinetic evaluation of a fixed-dose combination of the analytes in healthy male volunteers.

Natural Products; from the Laboratory to Clinical Practice.

It has been such a great honor to serve as the Guest Editor for this Special Issue, "Exploration on Pharmacokinetics and Pharmacodynamics of Natural Molecules: Current Status and Future Perspectives" [...].

Factors impacting job satisfaction among pharmacists in the Arab world: A qualitative study.

Purpose: This study was undertaken to investigate in-depth the factors impacting job satisfaction among pharmacists in the Arab world and the challenges they encounter in their career path. The outcome of this study should help the local policymakers to take corrective actions to improve pharmacist's satisfaction and therefore enhance quality of patient care. Method: This qualitative study collected responses of pharmacists from 12 Arab countries, as part of a large quantitative survey. Participants added comments to an optional open-ended question regarding work satisfaction. The Qualtrics Survey Software was used to collect the responses. The survey was distributed from March to May 2021 through multiple online channels for filling. The responses collected were analysed to develop themes. An inductive constructivist approach was used for the conceptual thematic analysis as the methodological orientation. Results: A total of 110 responses/comments were received from the study participants. The two largest practice settings of the participants were from hospitals (44.5%) and community pharmacies (28.2%). Almost 40% of responses came from pharmacists practising in Qatar (21.8%) and UAE (18.1%). The survey data demonstrated several reasons impacting job satisfaction among pharmacists practising in the Arab countries. Underestimation of the pharmacists' role, low salaries, lack of motivation and excessive workload were reported as major contributors to job dissatisfaction. On the other hand, professional commitment and the culture of the work setting were the major contributors to job satisfaction. Conclusions: The study provides valuable insights into the aspects concerning pharmacists' satisfaction in the Arab world. Policymakers and other stakeholders need to act upon aspects of pharmacists' job satisfaction and dissatisfaction to ensure potentially better working environment and patient outcomes.

The Modulation of Arachidonic Acid Metabolism and Blood Pressure-Lowering Effect of Honokiol in Spontaneously Hypertensive Rats.

BACKGROUND: Cardiovascular diseases have consistently been the leading cause of death in the United States over the last two decades, with 30% of the adult American population having hypertension. The metabolites of arachidonic acid (AA) in the kidney play an important role in blood pressure regulation. The present study investigates the antihypertensive effect of honokiol (HON), a naturally occurring polyphenol, and examines its correlation to the modulation of AA metabolism. METHODS: Spontaneously hypertensive rats (SHR) were randomly divided into four groups. Treatment groups were administered HON intraperitoneally at concentrations of 5, 20, and 50 mg/kg. Blood pressure was monitored at seven-day intervals. After a total of 3 weeks of treatment, the rats were euthanized and the kidney tissues were collected to examine the activity of the two major enzymes involved in AA metabolism in the kidney, namely cytochrome P450 (CYP)4A and soluble epoxide hydrolase (sEH). RESULTS: Rats treated with HON did not experience the rise in blood pressure observed in the untreated SHR. High-dose HON significantly reduced blood pressure and inhibited the activity and protein expression of the CYP4A enzyme in the rat kidney. The activity of the sEH enzyme in renal cytosol was significantly inhibited by medium and high doses of HON. CONCLUSION: Our data demonstrate the antihypertensive effect of HON and provide a novel mechanism for its underlying cardioprotective properties.

Catechin Reduces Blood Pressure in Spontaneously Hypertensive Rats through Modulation of Arachidonic Acid Metabolism.

(1) Background: hypertension affects approximately half of the adults in the United States (roughly 116 million). The cytochrome P450 (CYP)-mediated metabolism of arachidonic acid (AA) in the kidney has been found to play a major role in the pathogenesis of hypertension. This study examines the anti-hypertensive effect of the natural polyphenolic compound catechin (CAT) and investigates if it impacts the metabolism of AA in the kidney in comparison to captopril (CAP): a commonly used antihypertensive drug. (2) Methods: spontaneously hypertensive rats (SHR) were randomly divided into five groups. The treatment groups were administered CAT in drinking water at doses of 10 and 50 mg/kg. A positive control group received CAP at a dose of 10 mg/kg in the drinking water, and one group received both CAP and CAT at doses of 10 mg/kg and 50 mg/kg, respectively. Blood pressure was monitored weekly for five weeks. The activity of the two major enzymes involved in AA metabolism in the kidney, namely CYP4A and soluble epoxide hydrolase (sEH), were analyzed. (3) Results: CAP monotherapy was found to reduce blood pressure compared to the control untreated rats but did not demonstrate any effect on AA metabolism. Low- and high-dose CAT resisted the rise in blood pressure observed in the untreated SHR and significantly lowered blood pressure compared to the control group, respectively. Only rats treated with high CAT doses demonstrated significant inhibition of CYP4A and sEH enzyme activities. The coadministration of CAP and a high dose of CAT resulted in more pronounced blood pressure-lowering effects, but no more significant effects on AA metabolism were found compared to a high dose of CAT alone. (4) Conclusion: the modulation of AA metabolism in the kidney contributes, at least partially, to the blood pressure-lowering effect of CAT in SHR rats.

Mechanistic Basis for the Role of Phytochemicals in Inflammation-Associated Chronic Diseases.

Chronic inflammatory diseases occur in a large portion of the population and are associated with a poor diet. Key natural products found in fruits and vegetables may assist in lowering inflammation associated with chronic diseases such as obesity, diabetes, cardiovascular diseases, and cancer. This review seeks to examine the roles of several natural products, resveratrol (RES), quercetin (QUE), curcumin (CUR), piperine (PIP), epigallocatechin gallate (EGCG), and gingerol (GIN), in their ability to attenuate inflammatory markers in specific diseases states. Additionally, we will discuss findings in past and ongoing clinical trials, detail possible phytochemical-drug interactions, and provide a brief resource for researchers and healthcare professionals on natural product and supplement regulation as well as names of databases with information on efficacy, indications, and natural product-drug interactions. As diet and over-the-counter supplement use are modifiable factors and patients are interested in using complementary and alternative therapies, understanding the mechanisms by which natural products have demonstrated efficacy and the types of drugs they interact with and knowing where to find information on herbs and supplements is important for practicing healthcare providers and researchers interested in this field.

Development and validation of a sensitive and specific LC-MS/MS cocktail assay for CYP450 enzymes: Application to study the effect of catechin on rat hepatic CYP activity.

A sensitive and specific liquid chromatography tandem mass spectrometric (LC-MS/MS) method that enables the simultaneous quantification of probe substrates and metabolites of cytochrome P450 (CYP) enzymes was developed and validated. These substrates (metabolites)-coumarin (7-hydroxycoumarin), tolbutamide (4-hydroxytolbutamide), S-mephenytoin (4-hydroxymephenytoin), dextromethorphan (dextrorphan), and testosterone (6ß-hydroxytestosterone)-were utilized as markers for the activities of the major human CYP enzymes CYP2A6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, respectively. Analytes were separated on Kinetex C18 column (2.1 × 50 mm, 5 µm) using a binary gradient mobile phase of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Metabolites were detected and quantified by MS using multiple reaction monitoring at m/z 163 → 107.2 for 7-hydroxycoumarin, m/z 235 → 150.1 for 4-hydroxymephenytoin, m/z 287 → 171 for 4-hydroxytolbutamide, m/z 258 → 157.1 for dextrorphan, m/z 305 → 269 for 6ß-hydroxytestosterone, and m/z 237 → 194 for the internal standard. The assay exhibited good linearity over a range of 10-500 ng/mL with acceptable accuracy and precision criteria. As a proof of concept, the developed cocktail assay was successfully used to examine the potential impact of catechin on the activity of the major rat liver CYP enzymes.

The Antihypertensive Effect of Quercetin in Young Spontaneously Hypertensive Rats; Role of Arachidonic Acid Metabolism.

Hypertension affects almost 50% of the adult American population. Metabolites of arachidonic acid (AA) in the kidney play an important role in blood pressure regulation. The present study investigates the blood pressure-lowering potential of quercetin (QR), a naturally occurring polyphenol, and examines its correlation to the modulation of AA metabolism. Spontaneously hypertensive rats (SHR) were randomly divided into four groups. Treatment groups were administered QR in drinking water at concentrations of 10, 30, and 60 mg/L. Blood pressure was monitored at seven-day intervals. After a total of seven weeks of treatment, rats were killed and kidney tissues were collected to examine the activity of the two major enzymes involved in AA metabolism in the kidney, namely cytochrome P450 (CYP)4A and soluble epoxide hydrolase (sEH). Medium- and high-dose QR resisted the rise in blood pressure observed in the untreated SHR and significantly inhibited the activity of the CYP4A enzyme in renal cortical microsomes. The activity of the sEH enzyme in renal cortical cytosols was significantly inhibited only by the high QR dose. Our data not only demonstrate the antihypertensive effect of QR, but also provide a novel mechanism for its underlying cardioprotective properties.

Development and Validation of High-Throughput Bioanalytical Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) Method for the Quantification of Newly Synthesized Antitumor Carbonic Anhydrase Inhibitors in Human Plasma.

In the present study, a sensitive and fully validated bioanalytical high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the quantitative determination of three newly synthesized carbonic anhydrases inhibitors (CAIs) with potential antitumor activity in human plasma. The analytes and the internal standard (IS) were extracted using 1.5 mL acetonitrile from only 450 µL aliquots of human plasma to achieve the desired protein precipitation. Chromatographic separations were achieved on Phenomenex Kinetex® C18 column (100 × 4.6 mm, 2.6 µm) using a binary gradient elution mode with a run time of less than 6 min. The mobile phase consisted of solvent (A): 0.1% formic acid in 50% methanol and solvent B: 0.1% formic acid in acetonitrile (30:70, v/v), pumped at a flow rate of 0.8 mL/min. Detection was employed using triple quadrupole tandem mass spectrometer (API 3500) equipped with an electrospray ionization (ESI) source in the positive ion mode. Multiple reaction monitoring (MRM) mode was selected for quantitation through monitoring the precursor-to-parent ion transition at m/z 291.9 → 173.0, m/z 396.9 → 225.1, m/z 388.9 → 217.0, and m/z 146.9 → 91.0 for AW-9a, WES-1, WES-2, and Coumarin (IS), respectively. Linearity was computed using the weighted least-squares linear regression method (1/x2) over a concentration range of 1-1000, 2.5-800, and 5-500 ng/mL for AW-9a, WES-1, and WES-2; respectively. The bioanalytical LC-MS/MS method was fully validated as per U.S. Food and Drug Administration (FDA) guidelines with all respect to linearity, accuracy, precision, carry-over, selectivity, dilution integrity, and stability. The proposed LC-MS/MS method was applied successfully for the determination of all investigated drugs in spiked human plasma with no significant matrix effect, which is a crucial cornerstone in further therapeutic drug monitoring of newly developed therapeutic agents.

A new validated HPLC method for the determination of levodopa: Application to study the impact of ketogenic diet on the pharmacokinetics of levodopa in Parkinson's participants.

A simple, accurate, and reproducible HPLC-UV method has been developed and validated for the quantification of levodopa (l-Dopa) in human plasma. The method involves a simple protein precipitation procedure to extract both l-Dopa and methyldopa, the internal standard. The chromatographic analysis was achieved on a Shimadzu LC 20A HPLC system equipped with a Zorbax Eclipse XDB C18 column and an isocratic mobile phase consisting of 20 mm KH2 PO4 (pH 2.5) and methanol (95:5, v/v) run at a flow rate of 1 mL/min. The UV detection wavelength was set at 230 nm. The method exhibited good linearity (R2 > 0.999) over the assayed concentration range (0.1-10 µg/mL) and demonstrated good intra- and inter-day precision and accuracy (relative standard deviations and the deviation from predicted values were <15%). This method was also successfully applied for studying the potential effect of ketogenic diet on the pharmacokinetics of l-Dopa in Parkinson's participants. Our data analysis indicates that ketogenic diet does not significantly affect the pharmacokinetics of l-Dopa.

A new validated HPLC method for the determination of quercetin: Application to study pharmacokinetics in rats.

A simple, accurate, and reproducible high-performance liquid chromatography (HPLC) method has been developed and validated for the quantification of quercetin (QR) in rat plasma. The method involves a simple protein precipitation procedure to extract both QR and thymoquinone (TQ), the internal standard. The chromatographic analysis was achieved on a Shimadzu LC 20 A HPLC system equipped with a Supelcosil LC-18 T C18 column and an isocratic mobile phase consisting of 0.3% trichloroacetic acid in water and acetonitrile HPLC-grade (50:50, v/v) run at a flow rate of 0.9 mL/min for 13 min. The UV detection wavelength was set at 254 nm. The method exhibited good linearity (R2 > 0.994) over the assayed concentration range (0.10-25 µg/mL) and demonstrated good intra-day and inter-day precision and accuracy (relative standard deviations and the deviation from predicted values were <20%). This method was also successfully applied for studying the pharmacokinetics of QR in rats following a single oral dose of QR to evaluate its pharmacokinetic parameters in rats.

Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole.

Human exposure to trans-cinnamic aldehyde [t-CA; cinnamaldehyde; cinnamal; (E)-3-phenylprop-2-enal] is common through diet and through the use of cinnamon powder for diabetes and to provide flavor and scent in commercial products. We evaluated the likelihood of t-CA to influence metabolism by inhibition of P450 enzymes. IC50 values from recombinant enzymes indicated that an interaction is most probable for CYP2A6 (IC50 = 6.1 µM). t-CA was 10.5-fold more selective for human CYP2A6 than for CYP2E1; IC50 values for P450s 1A2, 2B6, 2C9, 2C19, 2D6, and 3A4 were 15.8-fold higher or more. t-CA is a type I ligand for CYP2A6 (KS = 14.9 µM). Inhibition of CYP2A6 by t-CA was metabolism-dependent; inhibition required NADPH and increased with time. Glutathione lessened the extent of inhibition modestly and statistically significantly. The carbon monoxide binding spectrum was dramatically diminished after exposure to NADPH and t-CA, suggesting degradation of the heme or CYP2A6 apoprotein. Using a static model and mechanism-based inhibition parameters (K(I) = 18.0 µM; k(inact) = 0.056 minute(-1)), changes in the area under the concentration-time curve (AUC) for nicotine and letrozole were predicted in the presence of t-CA (0.1 and 1 µM). The AUC fold-change ranged from 1.1 to 3.6. In summary, t-CA is a potential source of pharmacokinetic variability for CYP2A6 substrates due to metabolism-dependent inhibition, especially in scenarios when exposure to t-CA is elevated due to high dietary exposure, or when cinnamon is used as a treatment of specific disease states (e.g., diabetes).

A new validated HPLC method for the determination of sulforaphane: application to study pharmacokinetics of sulforaphane in rats.

A simple, accurate and reproducible high-performance liquid chromatography (HPLC) method has been developed and validated for the quantification of sulforaphane (SF) in rat plasma. The method involves a simple liquid-liquid extraction procedure to extract both SF and 7-hyrdoxycoumarin, the internal standard. The chromatographic analysis was achieved on a Shimadzu LC 20A HPLC system equipped with a Zorbax Eclipse XDB C18 column and an isocratic mobile phase consisting of 10 mm KH2 PO4 (pH 4.5) and acetonitrile HPLC grade (40:60, v/v) run at a flow rate of 1 mL/min for 10 min. The UV detection wavelength was set at 202 nm. The method exhibited good linearity (R(2) > 0.999) over the assayed concentration range (0.05-2 µg/mL) and demonstrated good intra- and inter-day precision and accuracy (relative standard deviations and the deviation from predicted values were <15%). This method was also successfully applied for studying the pharmacokinetics of SF in spontaneously hypertensive rats following single oral dietary doses of SF. The pharmacokinetics of SF show linear behavior at the dose range investigated in this study. Copyright © 2015 John Wiley & Sons, Ltd.

Dietary Doses of Sulforaphane Affect Hepatic Drug Metabolizing Enzymes in Spontaneously Hypertensive Rats.

We previously demonstrated that exposure of spontaneously hypertensive rats (SHR) to dietary doses of sulforaphane (SF) results in resisting the progressive rise in blood pressure that is normally seen in these rats. This study investigates the potential effect of SF on hepatic drug metabolizing enzymes (DME) in SHR. The activity and/or protein expression of selected cytochrome P450 (CYP) enzymes and microsomal epoxide hydrolase (mEH) were measured in hepatic microsomes using specific probe substrates and/or polyclonal antibodies. Cytosolic fraction was utilized to measure protein level and activity of major antioxidant systems. The high dose SF resulted in a significant reduction of activity and apoproteins level of CYP1A2 and CYP2C9 and activities of CYP2B1/2 and mEH. No effect of SF was observed on the rest of the studied CYP enzymes. Both doses of SF resulted in a significant induction of both hepatic glutathione level and activities of superoxide dismutase and catalase. Activities of hepatic glutathione-S-transferases, glutathione reductase, and glutathione peroxidase were significantly induced only with the high dose. This study demonstrates that dietary doses of SF modulate the activity or protein expression of DME. Additionally, induction of the impaired antioxidant system in SHR may explain the blood pressure lowering effect of SF in this rat model. Copyright © 2015 John Wiley & Sons, Ltd.

Diagnosis and Management of Daptomycin-Induced Acute Eosinophilic Pneumonia: A Case Report.

Daptomycin is a cyclic lipopeptide antibiotic that is indicated for the treatment of complicated skin infections and bacteremia caused by gram positive organisms. Acute eosinophilic pneumonia (AEP) is a rare, but serious adverse effect of daptomycin and caused by accumulation of eosinophils in the lung tissues, and can lead to respiratory failure. Early diagnosis and management of this condition is crucial to avoid severe complications, including death. Herein, we report a case of an elderly man who presented with signs and symptoms of AEP within two weeks of initiation of daptomycin for the treatment of MRSA bacteremia. The patient showed significant clinical improvement and decline in eosinophils upon discontinuation of daptomycin and starting a 5-day steroid course. Acute eosinophilic pneumonia should be kept in mind as a possible, although rare, adverse effect of daptomycin. Early recognition can be established through typical symptoms, eosinophilia, and chest X-ray showing pulmonary infiltrate. Rapid discontinuation of daptomycin with/without steroid therapy and supportive care usually results in significant clinical recover.

Adaptive Effects of Endocrine Hormones on Metabolism of Macronutrients during Fasting and Starvation: A Scoping Review.

Food deprivation can occur for different reasons. Fasting (<24 h duration) occurs to meet religious or well-being goals. Starvation (>1-day duration) occurs when there is intentional (hunger strike or treatment of a medical condition) or unintentional (anorexia nervosa, drought, epidemic famine, war, or natural disaster) food deprivation. A scoping review was undertaken using the PubMed database to explore 1805 abstracts and review 88 eligible full-text articles to explore the adaptive relationships that emerge between cortisol, insulin, glucagon, and thyroid hormones on the metabolic pathways of macronutrients in humans during fasting and starvation. The collected data indicate that fasting and starvation prime the human body to increase cortisol levels and decrease the insulin/glucagon ratio and triiodothyronine (T3) levels. During fasting, increased levels of cortisol and a decreased insulin/glucagon ratio enhance glycogenolysis and reduce the peripheral uptake of glucose and glycogenesis, whereas decreased T3 levels potentially reduce glycogenolysis. During starvation, increased levels of cortisol and a decreased insulin/glucagon ratio enhance lipolysis, proteolysis, fatty acid and amino acid oxidation, ketogenesis, and ureagenesis, and decreased T3 levels reduce thermogenesis. We present a potential crosstalk between T3 and the above hormones, including between T3 and leptin, to extend their adaptive roles in the metabolism of endogenous macronutrients during food deprivation.