Temporal Variation in the Interaction Between Calcium Channel Blockers and Morphine-Induced Analgesia

Circadian variations in the interaction between calcium channel blockers and morphine-induced analgesia were determined by the mouse hot-plate test. Calcium channel blockers diltiazem, verapamil, or nicardipine alone did not display any significant analgesic effect, but all of them potentiated morphine-induced analgesia when injected 30 min prior to morphine at most of the injection times. In terms of percent absolute potentiation, they produced more potentiation during the light period than darkness. Their potentiating effects decreased abruptly during darkness, and around the midtime of the dark period no significant potentiation of morphine-induced analgesia was observed. It is concluded that these fluctuations in the magnitude of interaction between calcium channel blockers and morphine must be taken into consideration particularly in studies dealing with the role of calcium in analgesia.     

Temporal Variation in Serum Nitrite Levels in Rats and Mice

Although considerable evidence implicates involvement of nitric oxide (NO) in circadian regulation, little is known about possible 24h variations in basal NO metabolism. In this study, daily variations in serum nitrite levels were studied in locally bred mice and rats during the months of September and October. The serum was separated from blood samples obtained at six different times of the day and night (lh, 5h, 9h, 13h, 17h, and 21h after lights off [HALO] from male albino mice and rats). As an index of in vivo NO generation, serum nitrite levels (determined by the diazotization method) in rats exhibited significant temporal fluctuation (unpaired Student t test), with the concentration highest at 5 HALO and 21 HALO and lowest at 9 HALO. No such temporal variation was detected in mice in these studies conducted on locally bred animals in the autumn. (Chwnobiology International, 16(4), 527-532, 1999)     

Serum thyroid hormone profile and trace elements in children receiving valproic acid therapy: A longitudinal and controlled study

Valproic acid (VPA) may affect thyroid hormone profile, causing alteration in serum trace elements concentrations. The aim of this study was to prospectively investigate this relationship in children receiving VPA monotherapy for a period up to 6 months. Serum thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroxine (T4), triiodothyronine (T3), thyroglobuline (TG), selenium (Se), zinc (Zn), and copper (Cu) levels were evaluated at baseline and at the 6th month in all the patients and in the control group. The mean Cu concentration in the 6th months of VPA therapy was significantly lower than that of the control group. TSH level was significantly increased in the patient group whereas FT4 was significantly decreased. The mean TSH level in the 6th month of VPA therapy was significantly higher than that of the control group, whereas mean T4 level was significantly lower. The Cu level in the 6th months of VPA therapy was positively correlated with T4 level. Δlog Cu and ΔTSH were negatively correlated. This study suggests that the alteration in the serum thyroid hormone profile during VPA therapy may result from the reduction in serum Cu levels.     

National adaptation and implementation of WHO Model List of Essential Medicines: A qualitative evidence synthesis

BackgroundThe World Health Organization Model List of Essential Medicines (WHO EML) has played a critical role in guiding the country-level selection and financing of medicines for more than 4 decades. It continues to be a relevant evidence-based policy that can support universal health coverage (UHC) and access to essential medicines. The objective of this review was to identify factors affecting adaptation and implementation of WHO EML at the national level.Methods and findingsWe conducted a qualitative evidence synthesis by searching 10 databases (including CINAHL, Embase, Ovid MEDLINE, Scopus, and Web of Science) through October 2021. Primary qualitative studies focused on country-level implementation of WHO EML were included. The qualitative findings were populated in the Supporting the Use of Research Evidence (SURE) framework, and key themes were identified through an iterative process. We appraised the papers using the Critical Appraisal Skills Programme (CASP) tool and assessed our confidence in the findings using the Grading of Recommendations Assessment, Development and Evaluation working group-Confidence in Evidence from Reviews of Qualitative research (GRADE-CERQual). We screened 1,567 unique citations, reviewed 183 full texts, and included 23 studies, from 30 settings. Non-English studies and experiences and perceptions of stakeholders published in gray literature were not collected.Our findings centered around 3 main ideas pertaining to national adaptation and implementation of WHO EML: (1) the importance of designing institutions, governance, and leadership for national medicines lists (NMLs), particularly the consideration of transparency, coordination capacity, legislative mechanisms, managing regional differences, and clinical guidance; (2) the capacity to manage evidence to inform NML updates, including processes for contextualizing global evidence, utilizing local data and expert knowledge, and assessing budget impact, to which locally relevant cost-effectiveness information plays an important role; and (3) the influence of NML on purchasing and prescribing by altering provider incentives, through linkages to systems for financing and procurement and donor influence.ConclusionsThis qualitative evidence synthesis underscores the complexity and interdependencies inherent to implementation of WHO EML. To maximize the value of NMLs, greater investments should be made in processes and institutions that are needed to support various stages of the implementation pathway from global norms to adjusting prescribed behavior. Moreover, further research on linkages between NMLs, procurement, and the availability of medicines will provide additional insight into optimal NML implementation.Protocol registryPROSPERO CRD42018104112

Elizabeth F Peacocke and colleagues review factors associated with adaptation and implementation of the WHO model list of essential medicines at the national level.     

Synthesis and antimicrobial activity of some novel phenyl and benzimidazole substituted benzyl ethers

In this study, a series of novel phenyl- and benzimidazole-substituted benzyl ethers were synthesized and evaluated for antibacterial and antifungal activities against Staphylococcus aureus, Methicillin-resistant S. aureus (MRSA), Escherichia coli, Candida albicans, and Candida krusei. Compound 6g exhibited the most potent antibacterial activity with lowest MIC values of 3.12 and 6.25 microg/mL against S. aureus and MRSA, respectively.