bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise training induces alteration of clock genes and myokines expression in tumor‐bearing mice
Authors: de Souza Teixeira Alexandre Abilio , Biondo Luana , Silveira Loreana Sanches , Lima Edson A. , Diniz Tiego A. , Lira Fabio Santos , Seelaender Marilia , Rosa Neto José Cesar
Published: October 2023

To investigate the impact of different exercise training schedules (following a fixed schedule or at random times of the day) on clock genes and myokine expression patterns in the skeletal muscle of tumor‐bearing mice. Mice were divided into three groups: tumor (LLC), tumor + exercise training (LLC + T) always performed at the same time of the day (ZT2) and exercise training at random times of the day (ZTAlt). Mice were inoculated subcutaneously with Lewis lung carcinoma cells. The gastrocnemius muscle was dissected and the clock gene expression (Clock/Per1/Per2/Per3/Rev‐Erbα/GAPDH) was investigated by quantitative reverse transcription polymerase chain reaction with SYBR® Green. Myokine content in muscle (tumour necrosis factor alpha/IL‐10/IL‐4) was assessed by enzyme‐linked immunosorbent assay. At the end of the protocol, the trained groups showed a reduction in total weight, when compared to Lewis lung carcinoma. Tumor weight was lower in the LLC + T (ZTAlt), when compared to LLC. Clock gene mRNA expression showed a significant increase for ZT20 in the groups that performed physical exercise at LLC + T (ZTAlt), when compared with LLC. The Per family showed increased mRNA expression in ZT4 in both trained mice groups, when compared with LLC. LLC + T (ZTAlt) presented reduction of the expression of anti‐inflammatory myokines (Il‐10/IL‐4) during the night, compared with LLC + T(ZT2). Exercise training is able to induce marked modification of clock gene expression and of the production of myokines, in a way that is dependent on schedule exercise training strategy. Taken together, the results show that exercise is a potent Zeitgeber and may thus contribute to change clock genes expression and myokines that are able to reduce the tumor weight.
pH‐Responsive Trihydroxylated Piperidines Rescue The Glucocerebrosidase Activity in Human Fibroblasts Bearing The Neuronopathic Gaucher‐Related L444P/L444P Mutations in GBA1 Gene
Authors: Davighi Maria Giulia , Matassini Camilla , Clemente Francesca , Paoli Paolo , Morrone Amelia , Cacciarini Martina , Goti Andrea , Cardona Francesca
Published: October 2023

Engineering bioactive iminosugars with pH‐responsive groups is an emerging approach to develop pharmacological chaperones (PCs) able to improve lysosomal trafficking and enzymatic activity rescue of mutated enzymes. The use of inexpensive l‐malic acid allowed introduction of orthoester units into the lipophilic chain of an enantiomerically pure iminosugar affording only two diastereoisomers contrary to previous related studies. The iminosugar was prepared stereoselectively from the chiral pool (d‐mannose) and chosen as the lead bioactive compound, to develop novel candidates for restoring the lysosomal enzyme glucocerebrosidase (GCase) activity. The stability of orthoester‐appended iminosugars was studied by 1H NMR spectroscopy both in neutral and acidic environments, and the loss of inhibitory activity with time in acid medium was demonstrated on cell lysates. Moreover, the ability to rescue GCase activity in the lysosomes as the result of a chaperoning effect was explored. A remarkable pharmacological chaperone activity was measured in fibroblasts hosting the homozygous L444P/L444P mutation, a cell line resistant to most PCs, besides the more commonly responding N370S mutation.
„Was es ist und was es war, das wird uns erst beim Abschied klar“ (Anonym)
Authors: Böck Barbara
Published: October 2023

No abstract.
Optimization of effecting parameters for flue gas desulfurization in a self‐priming venturi scrubber using response surface methodology
Authors: Bal Manisha , Das Payal , Meikap Bhim Charan
Published: October 2023

Hydrogen sulfide (H2S), a highly poisonous and corrosive gas, is regarded as a hazardous air pollutant with significant effects on human health. Hence, reduction of hydrogen sulfide (H2S) gas from the atmosphere is very essential. In the present work, self‐priming venturi scrubber is employed to extract H2S gas from the air. Response surface methodology (RSM) with a central composite design (CCD) has been selected to investigate maximizing the H2S removal efficiency by optimizing the process variables. Experiments were carried out by altering the throat gas velocity, outer cylinder liquid level and inlet concentration of H2S. The analysis of variance (ANOVA) test showed that the parameters had a significant effect on the efficiency of H2S removal. A quadratic equation has been developed that accurately predicts the percentage of removal efficiency. The appropriateness of the generated model has been verified by the value of higher R2 resulting from the regression analysis. According to the observations, the velocity of throat gas has the highest effect on the H2S removal efficiency, whereas inlet H2S concentration has the least effect.
Bibliometric analysis: Root and root canal morphology using cone‐beam computed tomography
Authors: Karobari Mohmed Isaqali , Alam Beenish Fatima , Bashir Raima , Fahim Muhammed Faisal , Mirza Mubashir Baig , Noorani Tahir Yusuf
Published: October 2023

Objectives

This bibliometric analysis aimed to evaluate the leading nations, authors, journals, institutes, highly cited publications, and most commonly used keywords concerning scientific publications based on root and root canal morphology using the CBCT.

Material and Methods

For this bibliometric analysis, an extensive search was carried out on September 25, 2023 using the Scopus database. Pertinent articles in the field were scrutinized after applying inclusion and exclusion criteria. Data were evaluated using Vosviewer and Microsoft Excel.

Results

A literature search revealed the initiation of scientific publication in 2008. Significant contributions made by Saudi Arabia, India, and China concerning the number of publications were seen. Similarly, Jazan University from SA was recognized as the leading institute. The Journal of Endodontics was the leading journal, while authors JNR Martins and G Gambarini produced the highest number of papers.

Conclusions

This bibliometric analysis demonstrated that scientific publications have increased tremendously since 2008. Significant contributions have been made by developing and developed nations. The Journal of Endodontics and Jazan University have been identified as the leading journal and institute.
CD72 is a pan‐tumor antigen associated to pediatric acute leukemia
Authors: Buldini Barbara , Faggin Giovanni , Porcù Elena , Scarparo Pamela , Polato Katia , Tregnago Claudia , Varotto Elena , Rizzardi Paolo , Rizzari Carmelo , Locatelli Franco , Biffi Alessandra , Pigazzi Martina
Published: October 2023

In the development of novel immunotherapeutic approaches, the step of target identification is a challenging process, because it aims at identifying robust tumor‐associated antigens (TAAs) specific for the pathological population and causing no off‐target effects. Here we propose CD72 as a novel and robust TAA for pediatric acute leukemias. We provided an outline of CD72 expression assessed by flow cytometry on a variety of cancer cell lines and primary samples, including normal bone marrow (BM) samples and hematopoietic stem and progenitor cells. We analyzed CD 72 expression on a cohort of 495 pathological pediatric BM aspirates, including: 215 B‐cell precursor acute lymphoblastic leukemias (BCP‐ALL), 156 acute myeloid leukemias (AMLs), 88 T‐lineage ALLs or lymphoblastic lymphomas with BM infiltration, 13 B‐lineage lymphoblastic lymphomas with BM infiltration, 9 myelodysplastic syndromes with increased blasts (5%–9% blasts on BM: MDS‐IB1) and 14 non‐hematopoietic solid tumors infiltrating BM. Results showed that CD72 is highly expressed in almost all BCP‐ALL and the majority of AML at diagnosis, including BCP‐ALL cases characterized by CD19 loss. These findings support a potential role for advanced diagnostics and novel immunotherapy approaches, providing a pan‐ALL and AML target.
Fibroblast‐derived growth factors and exosomes as cosmeceuticals
Authors: Mehta Rahul C. , Kadoya Kuniko , Maitra Prithwiraj , Goberdhan Lisa T. , Makino Elizabeth T. , Naughton Gail K. , Goldman Mitchel P.
Published: October 2023

Introduction

Fibroblast (FB)‐derived growth factors have been successfully used in skincare to improve the appearance of aged and photodamaged skin for over 20 years. Conditioned media from FB culture, used as a source of growth factors in these early products, also contain extracellular vesicles including bioactive exosomes. Exosomes are tiny extracellular vesicles that have been isolated from the secretome of human‐derived mesenchymal stem cells (MSC), adipose‐derived stem cells, or fibroblasts for potential clinical application in wound healing, skin rejuvenation, skin disease, pigmentation, and hair growth.

Purpose

Here, we review the potential application of dermal FB‐derived growth factors and exosomes in maintaining the structure and function of healthy skin. Specifically, we discuss how to collect and characterize FB‐derived exosomes, formulation considerations for skincare products that may contain exosomes, and provide preliminary data to support its clinical use in improving skin quality.

Results

Exosomes were successfully isolated from FB secretome and characterized for their content, markers, biological activity, and clinical effects. Condition of growth medium affected exosomes compositions and properties. Product containing 98 billion EVs /mL used twice a day for 12 weeks resulted in statistically significant improvement in all skin aging parameters tested including wrinkles, roughness, sagging and laxity.

Conclusion

Overall, active exosomes can be identified along with growth factors in the secretome of dermal fibroblasts and may provide an additional benefit for aging skin if its biological activity remains stable in the product formulation.
A scoping review of psychological interventions and outcomes for avoidant and restrictive food intake disorder (ARFID)
Authors: Willmott Emma , Dickinson Rachel , Hall Celine , Sadikovic Kevser , Wadhera Emily , Micali Nadia , Trompeter Nora , Jewell Tom
Published: October 2023

Objective

This scoping review identifies and describes psychological interventions for avoidant restrictive food intake disorder (ARFID) and summarizes how outcomes are measured across such interventions.

Method

Five databases (Cochrane, Embase, Medline, PsycInfo, Web of Science) were searched up to December 22, 2022. Studies were included if they reported on psychological interventions for ARFID. Studies were excluded if participants did not have an ARFID diagnosis and if psychological interventions were not delivered or detailed.

Results

Fifty studies met inclusion criteria; almost half were single‐case study designs (23 studies) and most studies reported on psychological interventions for children and adolescents with ARFID (42 studies). Behavioral interventions (16 studies), cognitive‐behavioral therapy (10 studies), and family therapy (5 studies), or combinations of these therapeutic approaches (19 studies) were delivered to support patients with ARFID. Many studies lacked validated measures, with outcomes most commonly assessed via physical health metrics such as weight.

Discussion

This review provides a comprehensive summary of psychological interventions for ARFID since its introduction to the DSM‐5. Across a range of psychological interventions and modalities for ARFID, there were common treatment components such as food exposure, psychoeducation, anxiety management, and family involvement. Currently, studies reporting on psychological interventions for ARFID are characterized by small samples and high levels of heterogeneity, including in how outcomes are measured. Based on reviewed studies, we outline suggestions for clinical practice and future research.

Public Significance

Avoidant restrictive food intake disorder (ARFID) is an eating disorder characterized by avoidance or restriction of food due to fear, sensory sensitivities, and/or a lack of interest in food. We reviewed the literature on psychological interventions for ARFID and the outcomes used to measure change. Several psychological interventions have been developed and applied to patients with ARFID. Outcome measurement varies widely and requires further development and greater consensus.
Hydroxynitrile Lyase Discovery, Engineering, and Promiscuity towards Asymmetric Synthesis: Recent Progress
Authors: Priya Badipatla Vishnu , Padhi Santosh Kumar
Published: October 2023

Hydroxynitrile lyases (HNLs) primarily catalyze the stereoselective synthesis of cyanohydrins, but some of them also carry out asymmetric nitroaldol synthesis (Henry reaction). By virtue of the importance of asymmetric C−C bond formation, and the wide application of chiral cyanohydrins and β‐nitroalcohols, HNLs have gained significance in organic synthesis. Over the years new HNLs have been discovered and their synthetic scope are evaluated. Engineering of HNLs has contributed towards increasing not only the catalytic toolbox but also broad substrate selectivity, stereoselectivity, enzyme stability, and application of the enzymes for different transformations other than the conventional ones. This review describes the recent discoveries of diverse hydroxynitrile lyases (HNLs) and the developments to date since 2016, with respect to their biocatalytic applications in the asymmetric synthesis using both natural and promiscuous reactions.
Simultaneous quantification of six flavouring agents in herbal freshness gel toothpaste by gas chromatography
Authors: Tiwari Sumit , Sareen Vishal , Sharma Yamini , Sindhi Neha , Bandyopadhyay Prasun , Mitra Ranjan
Published: October 2023

There are many methods reported to identify and quantify volatile compounds. Many of them are based on chromatographic techniques, such as high‐performance liquid chromatography (HPLC), gas chromatography with flame ionization detector (GC‐FID), and GC coupled with mass spectrometry (GC–MS). But among all GC‐FID and GC–MS are majorly used for the detection and quantification of volatile compounds. A new gas chromatographic method has been developed for simultaneous determination of six flavouring agents [menthol, benzyl alcohol, methyl salicylate, anethole, menthol carboxamide (WS‐3) and eugenol] in herbal freshness gel toothpaste. All six flavours were separated using a DB‐WAX (Agilent) capillary GC column (30 m × 0.25 mm × 0.25 μm) and flame ionization detector (FID). This method was validated for various parameters such as precision, linearity, accuracy, stability, robustness, limit of detection, and limit of quantification as per ICH guidelines, AOAC internationals Appendix K. All the validation parameters were found to be within acceptable limits. The method was successfully applied for the quantification of all flavouring agents in toothpaste formulations.
Factors associated with child and maternal dietary diversity in the urban areas of Bangladesh
Authors: Haque Sadika , Salman Md. , Hossain Md. Shakhawat , Saha Sourav Mohan , Farquhar Samantha , Hoque Md. Nazmul , Zaman Nafisa , Hira Fatema Tuj Zohora , Hasan Md. Mehedi
Published: October 2023

Dietary diversity is an indicator of nutrition that has been found positively associated with diet quality, micronutrient adequacy, and improved maternal health and child growth. Due to the cultural responsibility of women in providing food at the household level, their status is very important to perform this role. Hence, this study has been conducted on the status of dietary diversity of the mother and child to understand how it relates to various factors of women in urban settings. Data were obtained from 1978 mother–child pairs living in different cities in Bangladesh. The foods taken by the women and children were categorized into 10 and 7 groups to measure women's dietary diversity (WDD) and children's dietary diversity (CDD), respectively. The study found that more than three‐fourths of the mothers and half of the children had low dietary diversity. The household wealth holdings and access to resources by the women were found inadequate, while two‐thirds of them had the lowest to medium level of nutritional knowledge. The binomial logistic regression model was used to measure the factors influencing WDD and CDD. The findings also indicated that children's dietary diversity was influenced by the mother's age, education, supportive attitude and behavior of husband, and access to and control over resources. While the household wealth index can enhance both child and mother's dietary variety, nutrition knowledge, dietary counseling, and access to and control over resources can improve maternal dietary diversity. This study recommends improving women's socioeconomic status by increasing their wealth and access to resources and enhancing their nutrition knowledge by providing food and nutrition counseling.
The impact of integrated care on health care utilization and costs in a socially deprived urban area in Germany: A difference‐in‐differences approach within an event‐study framework
Authors: Ress Vanessa , Wild Eva‐Maria
Published: October 2023

We investigated the impact of an integrated care initiative in a socially deprived urban area in Germany. Using administrative data, we empirically assessed the causal effect of its two sub‐interventions, which differed by the extent to which their instruments targeted the supply and demand side of healthcare provision. We addressed confounding using propensity score matching via the Super Learner machine learning algorithm. For our baseline model, we used a two‐way fixed‐effects difference‐in‐differences approach to identify causal effects. We then employed difference‐in‐differences analyses within an event‐study framework to explore the heterogeneity of treatment effects over time, allowing us to disentangle the effects of the sub‐interventions and improve causal interpretation and generalizability. The initiative led to a significant increase in hospital and emergency admissions and non‐hospital outpatient visits, as well as inpatient, non‐hospital outpatient, and total costs. Increased utilization may indicate that the intervention improved access to care or identified unmet need.
Re‐emergence of Lassa fever in Nigeria: A new challenge for public health authorities
Authors: Naeem Aroma , Zahid Shafaq , Hafeez Muhammad Hassan , Bibi Arifa , Tabassum Shehroze , Akilimali Aymar
Published: October 2023

The Lassa virus is an RNA virus belonging to the Arenaviridae family. It is responsible for Lassa fever, an acute viral zoonosis of the severe hemorrhagic fever type with manifestations of fever, muscle pain, sore throat, nausea, vomiting, and chest and abdominal pain. Lassa fever is endemic in West Africa, where the first case was reported in 1969 in Lassa, a town in Nigeria, more than 50 years ago, and it is estimated that nearly 5000 deaths occur in West Africa each year. Nigeria is one of the endemic hotspots and has experienced numerous recurrent outbreaks of Lassa fever due to the increased multiplication of the host reservoir, Mastomys natalensis. For the Lassa epidemics in 2022 and January 2023 alone, Nigeria accounts for a quarter of the annual deaths from this disease. Poor lifestyle and hygiene, difficulty in diagnosis due to nonspecific symptomatology, lack of effective treatment based on clinical evidence, an ineffective human immunization program combined with a health system that is not adapted or equipped to control and prevent recurrent deadly epidemics, and an outdated regional disease surveillance system in West Africa are some of the challenges that must be overcome to rapidly and effectively eradicate this disease, whose area of spread is constantly expanding as a result of the movement of populations in the context of economic and socio‐cultural activities.
High‐performance ferroelectric based materials via high‐entropy strategy: Design, properties, and mechanism
Authors: Zhang Yueyun , Chen Liang , Liu Hui , Deng Shiqing , Qi He , Chen Jun
Published: October 2023

High‐performance ferroelectric materials are widely used in various electronic devices owing to the function of mutual conversion among different energies, which mainly relates to their special structure gene of polarization configuration. Recent researches show that the high‐entropy strategy has emerged as an effective and flexible approach for boosting physical properties in high‐entropy ferroelectrics via the delicate design of local polarization configurations and other intrinsic effects caused by entropy increment, such as entropy stabilization, lattice disorder, inhibition of grain coarsening, improved mechanical properties, cocktail effect, and so on. In this review, the recent research progress about high‐entropy ferroelectrics has been summarized, especially for the directional design of novel local polarization configurations according to the characteristics of different electrical properties such as high piezoelectricity, high‐efficiency energy storage, and large electrostriction, providing a guidance for designing and exploring more novel local polarization configurations in high‐entropy ferroelectrics for generating higher performance.

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Maximizing Patient Outcomes of Antiinfective Therapy
Authors: Dudley Michael N.
Published: October 2023

Drug treatment of infectious disease requires consideration of both short‐ and long‐term therapy. Although in most settings patients receive antimicrobials for acute events, long‐term management of certain infections with drugs that delay progression of the disease adds a new facet to pharmacotherapy. In the past, broad questions regarding efficacy were posed: a drug was evaluated as either effective or not effective for a particular disorder. The actual question is, in whom is a given drug at a given dosage effective? Antibiotic control, restriction, and pharmacokinetic dosing programs have been useful, but they are reactive as opposed to proactive. The expensive products of biotechnology and the availability of oral drugs with activity exceeding that of parenteral antimicrobials require a more expanded scope of clinical pharmacy practice where patients are identified for these therapies prospectively using statistical models based on disease and other readily identified factors. Predictor variables for patient outcomes such as retreatment with other antibiotics, rehospitalization, toxicity, and mortality following the use of new drugs should be identified. Maximizing these outcome measurements will involve strategies that integrate epidemiology and statistical modeling techniques with principles of pharmaceutical care.
Pharmacokinetic Considerations in Quinolone Therapy
Authors: Nightingale Charles H.
Published: October 2023

It is advisable to switch patients from parenteral to oral therapy as soon as practical. High volumes of distribution, coupled with relatively low protein binding, indicate that the quinolones are widely distributed outside extracellular fluid. Interactions with aluminum‐ or magnesium‐containing antacids may be avoided by administering the antacids at least 2 hours after quinolone dosing. Some quinolones with high bioavailability (e.g., ofloxacin) are absorbed as reliably and completely after oral administration as when given parenterally, and dosage adjustments for these agents are unnecessary after sequential therapy. Treatment strategies may differ according to the route of drug elimination, and dosage adjustments are required in patients with renal failure who receive quinolones excreted primarily by the kidneys. Theophylline interactions may be more problematic in patients given quinolones that are primarily metabolized by the liver. Quinolones, which have concentration‐dependent killing and a long postantibiotic effect, should be administered in the highest tolerated dosage. A method to assess the relative antibacterial efficacy of the quinolones uses the ratio of the Cmax:MIC90 of the organism, compared with a ratio derived from the NCCLS breakpoints for susceptibility.
Oligonucleotide Pharmacotherapy: An Antigene Strategy
Authors: Nagel Karen M. , Holstad Sheldon G. , Isenberg Keith E.
Published: October 2023

Oligonucleotide pharmacotherapy, although in a very preliminary stage, promises to provide new, highly specific tools for the treatment of human diseases, such as viral illnesses and cancer. The agents have several proposed mechanisms of action, including inhibition of translation, splicing, and transcription. In addition, the bioefficacy of oligonucleotides may be enhanced by phosphorothioates, methylphosphonates, and α‐oligonucleotides. The agents are delivered by the ex vivo or topical route, and new methods of administration are under study. It is predicted that within the decade these agents will be used routinely to treat several serious illnesses.
Neonatal Withdrawal Syndrome: Associated Drugs and Pharmacologic Management
Authors: Levy Maurice , Spino Michael
Published: October 2023

Use of addicting drugs among women during pregnancy exposes newborns to potentially serious disorders. A group of symptoms referred to as neonatal withdrawal syndrome (NWS) may occur in infants born to mothers addicted to certain drugs because, at birth, the infants suddenly are cut off from the drug supply. Classes of drugs that cause NWS are those that produce addiction in adults, including the opioids (heroin, methadone, morphine), barbiturates, alcohol, and benzodiazepines. Many of the manifestations of NWS occur regardless of the class of drug, including irritability, hyperactivity, abnormal sleep pattern, high‐pitched cry, tremor, vomiting, diarrhea, weight loss, and failure to gain weight. The fact that these symptoms are nonspecific makes it difficult to identify NWS unless it is specifically looked for. The onset, duration, and severity of the disorder differ based on such factors as the addictive drug used, time and amount of mother's last dose, and rate of elimination of the drug from the newborn. Pharmacologic intervention may be required to control severe symptoms and signs. The most common drugs used to modify withdrawal are phenobarbital, paregoric, chlorpromazine, and diazepam. Treatment is complicated by conflicting information on the effectiveness of various agents.
Comparison of Ramipril and Enalapril in Patients With Essential Hypertension
Authors: Ruddy Michael C. , Mroczek William J.
Published: October 2023

Study Objective. To compare the clinical safety and efficacy of ramipril, a new long‐acting nonsulfhydryl inhibitor of angiotensin‐converting enzyme (ACE), with enalapril.

Design. A randomized, double‐blind trial.

Setting. Multicenter trial involving 4 large teaching hospitals and 12 community medical centers.

Patients. One hundred fifty‐nine patients with mild to moderate essential hypertension were enrolled. Two patients were excluded from the efficacy analysis because they failed to return for follow‐up.

Interventions. Patients were randomized to receive ramipril 2.5, 5, or 10 mg, or enalapril 5, 10, or 20 mg once/day for 3 or 4 weeks.

Measurements and Main Results. At baseline, supine diastolic blood pressures ranged from 98–116 mm Hg. Supine and standing systolic blood pressures were reduced by 11.8 and 10.2 mm Hg with ramipril 10 mg (p≤0.001) and 9.3 and 10.7 mm Hg with enalapril 20 mg (p≤0.001). At the end of the 4‐week trial, patients in all six dosage groups had clinically and statistically significant reductions in supine diastolic blood pressure compared with baseline values. The agents did not differ significantly with respect to their blood pressure‐lowering effects. Both lowered plasma ACE activity; after 4 weeks, changes from baseline were highly significant for all dosage groups (p≤0.001).

Conclusion. Ramipril was as effective in reducing blood pressure and was as well tolerated as enalapril. A larger average decrease in plasma ACE activity was achieved with ramipril over all dosages (71%) compared with that for enalapril (48%), suggesting that ramipril has greater ACE inhibition in the circulation.
Low‐Volume Whole Bowel Irrigation and Salicylate Absorption: A Comparison With Ipecac‐Charcoal
Authors: Olsen Keith M. , Ma Frank H. , Ackerman Bruce H. , Stull Richard E.
Published: October 2023

Study Objective. To evaluate two methods of gastrointestinal decontamination, low‐volume whole bowel irrigation (WBI) and activated charcoal, for their ability to prevent absorption of salicylate.

Design. Randomized, two‐phase crossover study.

Setting. A clinical research unit in a university‐based teaching hospital.

Patients. Six healthy, volunteer men.

Interventions. Subjects were assigned to receive 3000 ml WBI or syrup of ipecac 30 ml followed by activated charcoal 50 g in sorbitol, and were crossed over to the other treatment phase after 1 week. All treatments began 30 minutes after ingestion of 3.25 g aspirin. Urine was collected over 24 hours for analysis of total urinary excretion of salicylate. Serial blood samples were collected for salicylate determination and were subjected to pharmacokinetic analysis.

Measurements and Main Results. Mean ± SD recovery of salicylate were WBI 48.6 ± 5.4% and ipecac‐charcoal 37.0 ± 2.6% from urine (p<0.01).

Conclusion. Ipecac‐charcoal produced a significantly lower salicylate absorption (peak concentration, AUC) than WBI (p<0.01) and thus was superior to low‐volume WBI.
Relationship Between Pain Severity and Serum β‐Endorphin Levels in Postoperative Patients
Authors: Leonard Theresa M. , Klem Stephen A. , Asher Marc A. , Rapoff Michael A. , Leff Richard D.
Published: October 2023

Study Objective. To examine the relationship among postoperative pain severity, serum β‐endorphin level, and serum morphine level in pediatric patients after posterior spinal fusion with instrumentation.

Design. A prospective study.

Setting. University‐based medical center.

Patients. Ten patients age 13–17 years admitted for posterior spinal fusion with instrumentation.

Interventions. Each subject was administered an initial dose of intravenous morphine 100 μg/kg, followed by a constant infusion of 50 μg/kg/hour. The primary physician was allowed to titrate the dosage as required to meet the patient's requirement for analgesia. Whole blood was obtained for the analysis of serum morphine and β‐endorphin levels preoperatively, after the initial morphine dose, 24 hours after initiation of the infusion, and before any change in dosage. At each blood sampling time, pain severity ratings were obtained from the subject, nurse, and parent using a 10‐point linear scale.

Measurements and Main Results. No statistical difference between serum β‐endorphin values preoperatively and after the initial dose of morphine was observed; mean values were 68 and 60 pg/ml, respectively. The relationships between serum β‐endorphin level and pain scores were statistically significant only for self (subject) pain scores (p=0.014, r=‐0.30). Mean serum morphine level was 21.9 ng/ml for patients with self pain scores of 4 or less.

Conclusion. The clinical usefulness of serum β‐endorphin as a measure of pain severity was not established under the experimental conditions of this study.
Potentially Serious Drug Interactions Secondary to High‐Dose Diltiazem Used in the Treatment of Pulmonary Hypertension
Authors: Clarke William R. , Horn John R. , Kawabori Isamu , Gurtel Sharon
Published: October 2023

Two patients had potentially serious drug interactions (phenytoin, digoxin) that were probably attributable to changes in pharmacokinetics and pharmacodynamics caused by high‐dose calcium channel blocker therapy (diltiazem) in the treatment of pulmonary hypertension. Even in the approved normal dosages for the treatment of angina and hypertension, calcium channel blockers are known to cause significant changes in the metabolism of other drugs. Currently, no data exist on the effects of the very high dosages of these drugs, administered to patients with pulmonary hypertension, on the metabolism and clearance of other agents, although, based on our experience and literature reports, recommendations for monitoring therapy can be made.
Cefepime Pharmacokinetics in Cystic Fibrosis
Authors: Hamelin Bettina A. , Moore Nathalie , Knupp Catherine A. , Ruel Michel , Vallée François , LeBel Marc
Published: October 2023

Study Objective. To determine the disposition of cefepime in patients with cystic fibrosis compared with healthy controls.

Design. Open‐label, single‐dose study.

Setting. Laboratoire de Pharmacocinétique Clinique, Université Laval, Québec, Canada.

Patients and Subjects. Twelve patients with the confirmed diagnosis of cystic fibrosis (CF) and 12 healthy volunteers. One subject with CF withdrew for personal reasons; the data of another patient were excluded from the evaluation of renal values due to incomplete urine collection.

Interventions. A single 2000‐mg dose of cefepime was administered as a 30‐minute intravenous infusion. Healthy subjects did not use any other drugs throughout the study. Those with CF refrained from taking prophylactic antibiotics prior to and during the study, but continued to use pancreatic enzymes, multivitamins, and β‐agonist and/or steroid inhalers. One patient continued insulin treatment.

Measurements and Main Results. Cefepime's maximum concentration was approximately 150 μg/ml at the end of the infusion, half‐life 2‐2.5 hours, and urinary recovery 80% in both groups. No statistically significant difference was seen in any of the pharmacokinetic values between the groups, except for the mean residence time (2.03 ± 0.26 vs 2.39 ± 0.37 hrs; p<0.02). Total clearance was 19% higher in patients with CF than in healthy volunteers (119.7 ± 20.1 vs 103.5 ± 19.8 ml/min), perhaps due to higher renal (95.1 ± 12.4 vs 85.1 ± 12.0 ml/min) and/or nonrenal (25.4 ± 13.1 vs 18.4 ± 12.0 ml/min) clearances in subjects with CF.

Conclusions. The disposition of cefepime is not significantly affected by CF, and dosage adjustment appears not to be necessary in these patients.
Racial Differences in the Pharmacokinetics of Methylprednisolone in Black and White Renal Transplant Recipients
Authors: Tornatore Kathleen M. , Reed Kristine A. , Venuto Rocco C.
Published: October 2023

Study Objective. To examine the comparative pharmacokinetics of long‐term methylprednisolone therapy in black and white renal transplant recipients.

Design. Comprehensive pharmacokinetic evaluations of patients who participated in our glucocorticoid‐monitoring program.

Setting. University‐based renal transplantation clinic.

Patients. Six white renal transplant recipients with stable renal function, sex‐and (approximate) age‐matched with six preselected black patients.

Interventions. The daily oral methylprednisolone dose for each patient was administered intravenously, and serial plasma samples were obtained over 24 hours.

Measurements and Main Results. Methylprednisolone was analyzed by high‐performance liquid chromatography. The drug's pharmacokinetics in black and white patients, respectively, were as follows: mean clearance 234 ± 124 and 472 ± 180 ml/hr/kg (p<0.05); volume of distribution 0.3‐2.0 and 0.8‐2.0 L/kg; and elimination rate constant 0.13‐0.41 and 0.27‐0.42 hour−1 (p<0.06). No statistical difference was noted in the last two parameters. The mean half‐life of 3.4 ± 1.4 hours in black patients compared with 2.1 ± 0.3 hours in white patients approached statistical significance (p<0.08).

Conclusions. These preliminary observations suggest that the disposition of methylprednisolone differs between black and white renal transplant recipients. The current method of prescribing glucocorticoids employs a fixed‐dose regimen that does not take these possible interracial differences into consideration. Incorporating the differences may allow for more individualized dosing and more efficacious use of the agent in this patient population.
Treatment of Acute Neuroleptic‐Induced Movement Disorders
Authors: Tonda Margaret E. , Guthrie Sally K.
Published: October 2023

Acute extrapyramidal syndromes (EPS), including dystonia, parkinsonism, and akathisia, are associated with the use of virtually all neuroleptic agents. They may be alleviated by reducing the neuroleptic dosage, switching to a lower‐potency drug, or administering an adjunctive agent such as an anticholinergic, amantadine, benzodiazepine, or β‐blocker. Akathisia may be only partly dispelled by anticholinergics; alternatives are β‐blockers, benzodiazepines, and clonidine. In patients receiving long‐term neuroleptic therapy, both the prophylactic use and the duration of treatment with concomitant anti‐EPS drugs are controversial. Administration of prophylactic anti‐EPS drugs should be based on the likelihood that the patient will develop EPS, as well as the risk of adverse reactions resulting from extended use of the agents in a specific patient. The decision to continue anti‐EPS therapy should be reevaluated frequently, especially in elderly patients.
Community Pharmacy Data Bases to Identify Patients at High Risk for Hypercholesterolemia
Authors: Gardner Stephanie F. , Skelton David R. , Rollins Sharon D. , Hastings Jan K.
Published: October 2023

We compared the effectiveness of selectively screening pharmacy data bases to identify patients with hypercholesterolemia with that of mass cholesterol screening. Screening data bases of four community pharmacies yielded 426 patients filling prescriptions for β‐blockers, thiazide diuretics, oral hypoglycemics, insulin, sublingual nitroglycerin, nicotine gum, or nicotine patches. They were invited to attend a cholesterol screening. Eighty‐eight of the contacted patients attended, as did 97 walk‐in persons. Cholesterol readings were higher in the contacted group (p=0.017). Borderline‐high cholesterol levels (200–239 mg/dl) were reported in 36.3% of the contacted group and 29.8% of the walk‐in group. High cholesterol levels (> 239 mg/dl) were reported in 31.8% and 18.6%, respectively Targeting certain drugs that directly contribute to raising cholesterol or indicate other risk factors for coronary artery disease (e.g., diabetes mellitus) was an effective method of identifying patients with hypercholesterolemia.
Single Daily Dosing of Aminoglycosides
Authors: Preston Sandra L. , Briceland Laurie L.
Published: October 2023

To evaluate the rationale behind dosing aminoglycosides as a single daily dose versus traditional dosing approaches, we conducted a MEDLINE search to identify all pertinent articles, and also reviewed the references of all articles. Single daily dosing of aminoglycosides is not a new concept, having been examined since 1974. The advantages of this regimen include optimum concentration‐dependent bactericidal activity, longer dosing intervals due to the postantibiotic effect (PAE), and prevention of bacterial adaptive resistance. Because of longer dosing intervals, toxicity may also be delayed or reduced. Costs may be reduced due to decreased monitoring and administration. Clinically, the regimen has been implemented in various patient populations with reported success. Questions remain, however, about optimum dose, peak and trough serum concentrations, and dose adjustment in patients with renal impairment or neutropenia. More clinical experience with this method in large numbers of patients has to be published. Pharmacists can be instrumental in monitoring patients receiving once‐daily therapy and by educating health care professionals as to the rationale behind the therapy.
Treatment of Depression With Cyproheptadine
Authors: Greenway Scott E. , Pack Allen T. , Greenway Frank L.
Published: October 2023

We evaluated the antidepressant activity of cyproheptadine HCl in six patients diagnosed with major depression. This was a double‐blind, placebo‐controlled, crossover trial with treatment order balanced and randomly assigned. The patients received 4 weeks of treatment with cyproheptadine HCl 4 mg 4 times/day or placebo, followed by 4 weeks of cyproheptadine HCl 8 mg 4 times/day or placebo, followed by a crossover to cyproheptadine HCl or placebo. Each subject had a Hamilton Depression Rating Scale assessment and a 1‐mg dexamethasone suppression test completed immediately before treatment and at 4‐week intervals throughout the study. Two patients had nonsuppressible dexamethasone suppression tests and could not tolerate cyproheptadine due to anxiety and irritability. Four patients had suppressible dexamethasone suppression tests and had lower scores on the Hamilton Depression Rating Scale during treatment with cyproheptadine (p<0.01, Student's t test for paired observations). Cyproheptadine HCl may be useful in treating a subset of patients with major depression who have a suppressible dexamethasone suppression test.
Insulin‐like Growth Factor 1, but Not Growth Hormone, Has In Vitro Proliferative Effects on Neonatal Foreskin Fibroblasts without Affecting 5‐α‐Reductase or Androgen Receptor Activity
Authors: DYKSTRA KENNETH D. , PAYNE A. MATTHEW , ABDELRAHIM MAGED , FRANCIS GARY L.
Published: October 2023

ABSTRACT: Clinical observation of patients with congenital growth hormone (GH) deficiency and Laron‐type dwarfism suggests that factors such as GH or insulin‐like growth factor 1 (IGF‐1) might, in addition to androgens, be needed for normal phallic growth. We speculated GH or IGF‐1 might have direct actions on genital tissues and performed the present study to evaluate the in vitro effects of GH and IGF‐1 on cultured neonatal foreskin fibroblasts. Cells derived from foreskins of normal newborns were studied between cell passages 6 and 15. Serum‐free media with and without 100 ng/ml GH, IGF‐1, or both were added 24 hours prior to and at the time of study. To determine the activity of 5‐alpha‐reductase (5‐α‐R), 3H‐testosterone (T; 2 nM) was added, and 5‐α‐R activity was calculated as femtomoles 3H‐dihydrotestosterone and 3H‐androstanediol produced/microgram DNA/hour. Androgen receptor (AR) binding was determined by the addition of 3H‐dihydrotestosterone (dHT; 0.03125–0.5 nM) in the presence and absence of a 200‐fold excess of unlabeled dHT. Specific binding was used in Scatchard analysis for determination of AR number (Bmax) and binding affinity (Kd). The rate of DNA synthesis was determined by incorporation of 3H‐thymidine (3H‐Thy) into trichloroacetic acid‐insoluble material. DNA and protein content were determined on cell lysates. IGF‐1, but not GH, had proliferative effects (significant increases in the rate of 3H‐Thy incorporation, DNA, and protein content) but no effect on 5‐α‐R activity, Bmax or Kd. This suggests that IGF‐1 has direct, in vitro, proliferative effects on genital tissue that are not mediated by changes in 5‐α‐R or AR.
Sertoli Cell Secreted Growth Factor Cellular Origin, Paracrine and Endocrine Regulation of Secretion
Authors: SHUBHADA SANKARARAMAN , GLINZ MAURUS , LAMB DOLORES J.
Published: October 2023

ABSTRACT: Rat and human Sertoli cells in culture secrete a growth factor, Serfoli cell secreted growth factor (SCSGF). The aims of the present study were (1) to evaluate other testicular cell types as additional sources of SCSGF, as well as their paracrine effect, and (2) to study the hormonal regulation of SCSGF secretion using an A431 cell growth assay. The Sertoli cell was the only testicular cell type tested that secreted SCSGF activity in vitro. Peritubular cells enhanced Sertoli cell attachment and SCSGF secretion. Spermatogenic cells had no effect. The secretion of SCSGF was specifically stimulated by follicle‐stimulating hormone (FSH) and testosterone. Treatment with agents that increase intracellular cAMP levels and adenosine stimulated the secretion of mitogenic activity into Sertoli cell‐conditioned medium by three‐ to fivefold. This growth factor, secreted by the Sertoli cell and regulated by FSH and testosterone, may play a critical role in the regulation of spermatogenesis.
Treatment of Idiopathic Erectile Dysfunction in Men with the Opiate Antagonist Naltrexone—A Double‐Blind Study
Authors: BRENNEMANN W. , STITZ B. , Van AHLEN H. , BRENSING K. A. , KLINGMÜLLER D.
Published: October 2023

ABSTRACT Opiate antagonists can indirectly stimulate the secretion of luteinizing hormone (LH) and testosterone, as well as sexual functions in animals and humans. We therefore treated 20 otherwise healthy men with idiopathic erectile dysfunction aged 46.3 ± 2.7 years (mean ± SE, range 23.9–63.3) in a double‐blind study with an opiate antagonist, naltrexone, or placebo. The erectile dysfunction of these men had persisted for 3.6 ± 0.5 years despite libido maintenance; standard procedures had excluded any organic causes. Trial duration was 12 weeks overall. After a 4‐week forerun, the patients received at first 25 mg naltrexone/day orally or placebo for 4 weeks followed by 4 weeks of a 50‐mg dose of naltrexone/day or placebo. Each day the patients filled out a questionnaire detailing libido, degree of erection, frequency of sexual intercourse, and spontaneous morning erections. Serum concentrations of gonadotropins and testosterone were determined radioimmunologically in the initial stage and at the end of each phase. Both patient collectives had similar initial factors. The group treated with naltrexone showed a significant rise in spontaneous early morning erections during the treatment: from 2.8 ± 0.3 to 4.2 ± 0.3 a week (P < 0.001). The placebo group showed no significant change in spontaneous erections (2.4 ± 0.3 and 2.6 ± 0.3, respectively). The subjective parameters, however, such as libido, degree of erection, and frequency of sexual intercourse showed no significant difference within each group. There was no difference in LH, follicle‐stimulating hormone, or testosterone concentrations in both groups.

Thus, treatment with naltrexone significantly raises the rate of spontaneous early morning erections when compared to controls. Other parameters, especially those of the frequency of sexual intercourse, were not significantly influenced by the dosage of the administered opiate antagonist The significance of the naltrexone‐induced rise in spontaneous morning erections requires more evaluation in a greater collective of patients with idiopathic erectile dysfunction.
Isolation and Characterization of Mitochondria from Turkey Spermatozoa
Authors: MCLEAN DEREK J. , KORN NANCY , PEREZ BENILDA S. , THURSTON RONALD J.
Published: October 2023

ABSTRACT A procedure was developed to rapidly isolate functional, intact mitochondria from turkey spermatozoa. Semen was collected from turkeys, pooled, and centrifuged to remove spermiophages and other cells. The sperm cells were then mechanically disrupted with a Dounce homogenizer, sonicated, and centrifuged using a discontinuous Percoll gradient. Electron microscopy revealed morphologically intact mitochondria. The isolated mitochondria exhibited cytochrome oxidase activity, oxygen consumption, and were stained by rhodamine 123, a fluorescent stain specific for functional mitochondria in eukaryotic cells. Mitochondrial DNA (mtDNA) was isolated and purified, and the genome was determined to be 16.457 ± 0.07 kbp. Restriction fragment patterns were identified using the endonucleases EcoR1, HindIII, and BamH1. Mitochondrial DNA was also purified from turkey liver and testis, and no differences in the restriction enzyme patterns were found between somatic and germ cell mtDNA. It is concluded that mitochondria can be isolated from spermatozoa for metabolic or genetic study.