Protective effect of ZYMT, a traditional Chinese patent medicine in a mouse model of retinitis pigmentosa.

Retinitis pigmentosa (RP) is the most common genetic disorder that causes blindness. At present, there exists no remedy for the disease. The aim of the current research was to investigate the protective effect of Zhangyanming Tablets (ZYMT) in a mouse model of RP, and explore the underlying mechanism. Eighty RP mice were randomly divided into two groups. The mice in ZYMT group were administered with ZYMT suspension(0.0378 g/mL), while the mice in model group were given the same volume of distilled water. At day 7 and day 14 after intervention, electroretinogram (ERG), fundus photography, and histological examination were used to assess the retinal function and structure. TUNEL, immunofluorescence and qPCR were used to evaluate cell apoptosis and expressions of Sirt1, Iba1, Bcl-2, Bax and Caspase-3. A significantly shortened latency of ERG waves was observed in ZYMT-treated mice, in comparison to those in the model group (P < 0.05). Histologically, ultrastructure of the retina was better preserved, and the outer nuclear layer (ONL) exhibited marked increase in thickness and cell count in ZYMP group (P < 0.05). The apoptosis rate was decreased markedly in ZYMT group. Immunofluorescence analysis showed that the expressions of Iba1 and Bcl-2 in the retina were increased, Bax and Caspase-3 were decreased after ZYMT intervention, while the qPCR revealed that the expressions of Iba1 and Sirt1 were significantly increased (P < 0.05). This study indicated that ZYMT has protective effect on retinal function and morphology of inherited RP mice in the early stage, possibly mediated via the regulation of antioxidant and anti-/pro-apoptotic factors expressions.

Endophytic Fungi and Secondary Metabolites of Rehmannia Glutinosa Based on Traditional Chinese Medicine Fingerprints.

Research on the active components of medicinal plants has always been the focus of research, and research on the active components of medicinal plant endophytic fungi and their secondary metabolites has also attracted widespread attention. Endophytic fungi of medicinal plants are widely distributed and are ubiquitous in various biological groups in nature. Rehmannia glutinosa contains a variety of active ingredients, which are regarded as the top grade of Chinese medicinal materials. It is of certain significance to study endophytic fungi and their metabolites of Rehmannia glutinosa. In this paper, endophytic fungi and their secondary metabolites of Rehmannia glutinosa were studied using fingerprint technology, which initially understands the diversity of endophytic fungi in Rehmannia glutinosa. In this paper, the roots and leaves of Rehmannia glutinosa were used as experimental materials. The fungi were cultured in the medium, the fungi were isolated and purified by the tissue block method, the fungal growth of Rehmannia glutinosa in different parts was determined, and the types of endophytic fungi were identified by microscopic identification and fingerprinting. The isolated strains were tested for biological activity using oryza oryzae spores, and highly active strains were screened. Fermentation products of endophytic fungi were separated and purified by chromatography, and the structure of the compounds was identified by nuclear magnetic resonance spectroscopy. Through the above studies, the population structure of endophytic fungi of Rehmannia glutinosa was determined, 3 highly active strains were found, and the structures of 7 endophytic fungi metabolites were identified, of which 3 were newly discovered compounds.

Safety Threshold Considerations for Sunscreen Systemic Exposure: A Simulation Study.

Sunscreens are regulated as over-the-counter drugs in the United States. Some sunscreen ingredients are absorbed into the systemic circulation, which raises concerns about the safety of these drugs. There is limited information on the systemic exposure for most sunscreen ingredients. This report estimates the systemic absorption of two sunscreen active ingredients, oxybenzone and enzacamene, by developing a pharmacokinetic model from published sunscreen absorption data and compares the results with safety thresholds proposed by the US Food and Drug Administration and in the literature. Our analysis indicates that systemic absorption can be substantial, and evaluation of the systemic exposure of sunscreen ingredients is warranted to better assess any long-term risks of use.

Skin Barrier Health: Regulation and Repair of the Stratum Corneum and the Role of Over-the-Counter Skin Care.

The epidermis functions as a physical barrier that separates the inner body from the outside environment. The outermost layer of the epidermis, the stratum corneum, plays a key role in maintaining this barrier. There are numerous biochemical changes that take place to and in the keratinocyte as it migrates from the bottom, or startum basale, to the top layer of the epidermis in order for this barrier to function appropriately. In addition, external and internal factors, such as irritants and underlying medical diseases, can also affect the stratum corneum, both of which can potentially lead to disruption of barrier function and ultimately skin pathology. In this article, we will review keratinocyte biology as it relates to the formation and function of the stratum corneum. We will also review stratum corneum structure, physiology, and the impact of chemical agents and defective stratum corneum components that can lead to skin disease. Finally, we will briefly discuss how moisturizers repair defects in the stratum corneum and restore barrier function.

J Drugs Dermatol. 2016;15(9):1047-1051.

Alcohol-medical drug interactions.

Concomitant use of alcohol and medications may lead to potentially serious medical conditions. Increasing prescription medication abuse in today's society necessitates a deeper understanding of the mechanisms involved in alcohol-medication interactions in order to help prevent adverse events. Interactions of medications with alcohol result in altered bioavailability of the medication or alcohol (pharmacokinetic interactions) or modification of the effects at receptor or ion channel sites to alter behavioral or physical outcome (pharmacodynamic interactions). The nature of pharmacokinetic or pharmacodynamic interactions involved in alcohol-medication interactions may differ between acute and chronic alcohol use and be influenced by race, gender, or environmental or genetic factors. This review focuses on the mechanisms underlying pharmacokinetic and pharmacodynamic interactions between alcohol and medications and provides examples for such interactions from replicated research studies. In conclusion, further translational research is needed to address several gaps in our current knowledge of alcohol-medication interactions, including those under various pathologic conditions.

Medication pitfalls in the CKD clinic: case presentations.

The kidney plays a major role in pharmacokinetics and pharmacodynamics of drugs; therefore, medication errors can result from failure to properly adjust medications in patients with CKD. It is the responsibility of all health-care providers to work collectively when reviewing medications, initiating new medications, and adjusting doses of current medications. Awareness of appropriate dosing recommendations can significantly decrease medication error-associated morbidity, mortality, and cost.

HPLC-method for deliberation of drug mammary transfer-evaluation of over-the-counter drugs (Loxonin(®)-S, Bufferin(®) A) in mother mice.

Loxoprofen (Loxonin(®)), an antipyretic painkiller, was approved as an over-the-counter (OTC) drug (Loxonin(®)-S) in January 2011. With regard to self-medication using OTC drugs, the information that pharmacists provide to consumers is very important. Although loxoprofen is a very versatile drug and can be used during breastfeeding, information regarding its mammary gland transfer is inadequate. In this study, we established a simple method to evaluate mammary transfer of drugs, and compared loxoprofen's mammary gland transfer with that of aspirin. Loxoprofen 12 mg/kg and aspirin 132 mg/kg was orally administered to mother mice (ddY), and blood and milk samples were collected. Twenty microliters of ethanol was added to the blood and milk samples (10 µL), and the mixture was centrifuged for 15 min (12000 g); the supernatant was analyzed by high-performance liquid chromatography. Since aspirin was immediately metabolized, we analyzed salicylic acid concentrations. Maximum concentration of loxoprofen was observed at around 15 min after its oral administration, with the concentrations in the blood and milk being 2.9 and 0.5 µg/mL, respectively. The drug was metabolized promptly thereafter. In contrast, maximum concentration of salicylic acid was observed at 30 min after aspirin administration, with the concentrations in the blood and milk being 187.2 and 64.4 µg/mL, respectively. These concentrations remained constant from 60 to 120 min. Salicylic acid could be detected 240 min after aspirin administration. Thus, mammary gland transfer of loxoprofen is lower than that of aspirin, suggesting that loxoprofen does not accumulate in milk.

'Sweet Dreams', 'Happy Days' and elevated 24-h urine 5-hydroxyindoleacetic acid excretion.

We report two patients with markedly elevated 24-h urine 5-hydroxyindoleacetic acid (5-HIAA) excretion due to over-the-counter (OTC) self-medication with 5-hydroxytryptophan (5-HTP). It is important to recognize that OTC medication may cause increased 'false-positive' 5-HIAA excretion to prevent undue patient anxiety and unnecessary further investigation for carcinoid disease. Discordance between chromogranin A and 24-h urine 5-HIAA results should alert to the possibility of false-positive or -negative laboratory results.

Absence of 'over-the-counter' medicinal products in on-line prescription records: a risk factor of overlooking interactions in the elderly.

PURPOSE: To assess possible origins of harmful interactions in elderly patients arising from the current absence of information on over-the-counter (OTC) medicines in the Danish 'on-line prescription record'. METHODS: Information on current use of prescription drugs and OTC medicinal products (non-prescription drugs, herbal medicine, dietary supplements, and others) was collected by home visit interviews. The latter OTC products were not listed in an on-line prescription record that covered the previous two years. Information on interactions between OTC medicines and between OTC products and prescription drugs was obtained from the Danish National Drug Interaction Database. RESULTS: Of the 309 patients recruited (median age 75 years, interquartile range (IQR) 70-81), 229 (74%) used 568 OTC medicines not listed in the Danish 'on-line prescription record', amongst which we identified 166 potential interactions - between OTC treatments or between OTC and prescription drugs. Fifty percent of patients taking OTC medicines were exposed to potential interactions, i.e. one to three instances per patient. Twenty-five percent of patients exposed to interactions experienced interaction listed as 'Can be used with certain precautions'. CONCLUSION: The absence of information on OTC products in an on-line prescription record entails a risk of overlooking interactions in elderly patients. Such products should be included in on-line medication records to prevent adverse effects from interactions. However, online medication records are not available in all countries and as inclusion of data on OTC drugs seem not to be feasible presently. Still, it is highly recommended that the patient's drug list is reviewed on a regular basis.

The screening of forensic blood, urine, and tissue specimens for xenobiotics using ion-trap liquid chromatography-tandem mass spectrometry.

During the investigation of aviation accidents, postmortem specimens from accident victims including blood, urine, and tissue are submitted to the Federal Aviation Administration's Civil Aerospace Medical Institute (CAMI) for toxicological analysis. The first, and perhaps most important, step in the analysis process is the initial screening of biological specimens for illicit, medically prescribed, and over-the-counter compounds that may be present and potentially be a cause and/or factor in the accident. Currently, our general unknown screening (GUS) procedure involves, in part, both gas chromatography-mass spectrometry (GC-MS) and liquid chromatography (LC) with both diode-array detection (DAD) and fluorescence detection. Both GC and LC techniques have inherent limitations that prevent the detection of certain types of compounds. The decreased specificity and sensitivity of LC-DAD has been an impediment to the existing GUS procedure. Therefore, our laboratory set out to develop and validate an LC-MS-MS procedure that is superior to LC-DAD. The limits of detection of 359 forensically important xenobiotics have been established following solid-phase extraction from whole blood and analysis by LC-MS-MS. Although whole blood was used as the matrix during instrument validation, the method has been successfully applied to both forensic urine and tissue specimens as well.

A fatality due to cyproheptadine and citalopram.

Cyproheptadine (Periactin) is a first-generation antihistamine available in over-the-counter cold medications and is used to treat allergic-type symptoms. Although antihistamines in general have long been known to cause serious side effects, especially when taken in overdose, few reports that specifically address cyproheptadine-related fatalities exist. A 42-year-old healthy female was found dead at her home with no anatomic cause of death and a recent history of suicidal ideations. Toxicology revealed cyproheptadine and citalopram in the femoral postmortem blood at concentrations of 0.49 and 2.3 mg/L, respectively. Vitreous, urine, and bile analysis were also performed, yielding concentrations of < 0.04 and 0.80 mg/L in the vitreous for cyproheptadine and citalopram, respectively; 0.23 and 8.2 mg/L in the urine; and 30.7 and 9.0 mg/L in the bile. The cause of death was determined to be cyproheptadine and citalopram intoxication, and the manner was ruled a suicide. Although cyproheptadine is widely available in the United States and Europe, there are only two published fatalities due to this antihistamine and only one that specifically cites blood and tissue concentrations. Therefore, this case study will be beneficial to the forensic toxicology community by providing additional information regarding postmortem interpretation.

Polymorphic drug metabolizing CYP-enzymes--a pathogenic factor in oral lichen planus?

BACKGROUND: Oral lichen planus (OLP) is a chronic mucosal disease with a characteristic clinical phenotype. Environmental exposures, e.g. drugs have been associated with the pathogenesis. OBJECTIVES: To test the hypothesis that some OLP lesions have a pharmacological pathogenesis related to polymorphisms of the cytochrome P450 enzymes (CYPs) resulting in poor or intermediate CYP metabolism. METHODS: One hundred and twenty patients with OLP and 180 gender-matched controls without OLP were genotyped for CYP2C9, CYP2C19, and CYP2D6 alleles with absent or reduced function. RESULTS: The prevalence of poor or intermediate metabolizers was not higher among the OLPs as compared with the controls; however, there were higher numbers of variant CYP2D6 genotypes among the OLP females (P < 0.05). There were no differences between the groups with regard to intake of drugs metabolized by polymorphic CYPs or drug or herbal products inhibiting CYPs. The prevalence of CYP2D6*4 alleles among the OLPs was higher [28%; 95% confidence interval (CI) 20-36%] than previously reported among Danes (19%; 95% CI 17-22%). Fifty per cent of the OLPs had a CYP2D6*4 genotype as compared with 30% in the background population (P = 0.0001). The CYP2D6*4 protein has sequence homology with human herpes simplex virus type 1 (HSV1) and Candida albicans, which may result in molecular mimicry. CONCLUSION: It was not possible to substantiate a pharmacological pathogenesis of OLP based on poor or intermediate CYP metabolism. However, molecular mimicry between CYP2D6, in particular CYP2D6*4, and common oral pathogens may be involved in the pathogenesis of OLP.

Diphenhydramine abuse and detoxification: a brief review and case report.

Many medicines available over the counter from pharmacies are known to have abuse potential, including diphenhydramine (DPH), an antihistamine with antimuscarinic properties used for the treatment of insomnia. We present a brief review of the literature describing DPH abuse, and report the case of GF, a 56 year old woman who was admitted to an inpatient addictions unit for detoxification from DPH. A literature search revealed five case reports of DPH abuse including a total of six patients, published between 1986 and 2001. All reported cases exhibited features of DSM-IV criteria for substance dependence, and there was an apparent link with antipsychotic usage. GF was treated with antipsychotics, and was using up to thirty 50 mg DPH tablets each day. She described feeling 'good and calm' and 'it stopped the tremors'. GF tolerated a gradual dose reduction schedule, and completed the detoxification programme relatively comfortably. She was discharged from the inpatient detoxification unit as planned, and had not relapsed at six months. The described case report highlights the importance of enquiring about non prescribed medication when taking a drug history. Similarly community pharmacists and GPs should be vigilant to excessive requests for DPH, particularly in patients with a psychotic illness.

Unexpected infant deaths associated with use of cough and cold medications.

OBJECTIVE: The objective of this study was to determine whether caregivers had given infants who died unexpectedly over-the-counter cough and cold medications before the infant deaths to identify sociodemographic risk factors for their use. METHODS: The Arizona Child Fatality Review Program reviews the circumstances surrounding every child death that occurs in the state each year. By statute, the multidisciplinary review teams have access to all medical charts, autopsy reports, law enforcement reports, and other records for their review and use these data to determine the cause of death and its preventability. The data on all infants who died unexpectedly in 2006 and had an autopsy and postmortem toxicologic studies were reviewed for this analysis. RESULTS: Ten unexpected infant deaths that were associated with cold-medication use were identified. The infants ranged in age from 17 days to 10 months. Postmortem toxicology testing found evidence of recent administration of pseudoephedrine, antihistamine, dextromethorphan, and/or other cold-medication ingredients in these infants. The families who used these medications were poor and publicly insured, and 50% of them had limited English proficiency. Only 4 of these infants had received medical care for their current illness before their death. The over-the-counter cough and cold medication had been prescribed by a clinician for only 1 of these infants. CONCLUSIONS: Review of these infants' deaths raises concern about the role of the over-the-counter cough and cold medications in these deaths. These findings support the recommendation that such medications not be given to infants. In addition, these findings suggest that warnings on these medications "to consult a clinician" before use are not being followed by parents. Educational campaigns to decrease the use of over-the-counter cough and cold medications in infants need to be increased.

Increase of urinary 5-hydroxyindoleacetic acid excretion but not serum chromogranin A following over-the-counter 5-hydroxytryptophan intake.

BACKGROUND: 5-hydroxyindoleacetic acid (5-HIAA) excretion is commonly measured for biochemical detection of carcinoid tumours. A 77-year-old woman was referred for elevated 24 h urine 5-HIAA excretion (510 micromol/day; normal is less than 45 micromol/day) and serum chromogranin A (CgA) (72.1 U/L; normal is less than 18 U/L), both subsequently normalized after discontinuation of 5-hydroxytryptophan (5-HTP). 5-HTP, a precursor of serotonin, is not commonly listed as a substance that increases 5-HIAA levels in urine. The effect of 5-HTP on CgA has not been previously described. OBJECTIVES: To determine whether, and to what extent, oral 5-HTP increases urine 5-HIAA excretion and serum CgA levels in healthy volunteers. PATIENTS AND METHODS: A randomized, prospective, double-blind, placebo-controlled crossover study, with a four-day washout period, was performed in a general community setting. Eight healthy subjects aged 22 to 58 years were recruited by advertising. Bedtime ingestion of 5-HTP 100 mg/day was compared with placebo ingestion for 10 days. Twenty-four hour urine excretion of 5-HIAA and serum CgA were the main outcome measures. RESULTS: Median (range) urinary 5-HIAA excretion was 204 micromol/day (22 micromol/day to 459 micromol/day) during 5-HTP intake, compared with 18 micromol/day (12 micromol/day to 36 micromol/day) during placebo intake (P=0.017). 5-HTP did not affect clinical symptoms or serum CgA levels. CONCLUSIONS: Oral 5-HTP increases urinary 5-HIAA excretion with considerable interindividual variation. In a small number of subjects, oral 5-HTP did not affect serum CgA levels. Therefore, increased 5-HIAA levels with normal CgA levels may suggest 5-HTP ingestion. The use of over-the-counter 5-HTP should be excluded as the cause of increased urinary 5-HIAA levels before initiating diagnostic tests to search for a carcinoid tumour. 5-HTP should be added to popular references as a substance that may cause increased 5-HIAA excretion.

Over-the-counter cold medications-postmortem findings in infants and the relationship to cause of death.

The Montgomery County Coroner's Office has encountered a series of 10 infant deaths over an 8-month period in infants under 12 months old with toxicology findings that include a variety of drugs commonly found in over-the-counter (OTC) cold medications. The drugs detected were ephedrine, pseudoephedrine, dextromethorphan, diphenhydramine, chlorpheniramine, brompheniramine, ethanol, carbinoxamine, levorphanol, acetaminophen, and the anti-emetic metoclopramide. Toxicology findings were confirmed in 2 different matrices in 9 of the 10 cases and by 2 different analytical methods. The blood concentrations of the drugs and the case histories, as well as the cause of death for each infant, if available, will be given. The majority of these deaths were either toxicity from the OTC cold medications directly or as a contributory factor in the cause of death. Only two of the cases were the result of possible child abuse. Caregivers may be under the mistaken notion that OTC cold medications formulated for children are also safe for use in infants. These cases demonstrate that not only is administration of some OTC cold medications not safe, but use of OTC cold medications in infants can result in toxicity that can lead to death.

Resolution of ephedrine stones with dissolution therapy.

A patient with a history of ingesting large quantities of an over-the-counter stimulant developed renal calculi that on further analysis, after stone passage, revealed increased amounts of ephedrine. Over the course of 7 months, all of the patient's ephedrine stones were managed successfully by alkalinization. Similar to previously reported ephedrine calculi, these stones were radiolucent on x-ray imaging, but their course was monitored on serial nonenhanced computed tomography scans. We believe this to be the first reported use of alkaline therapy for the dissolution of renal stones containing ephedrine.

Consumption of prescribed and over-the-counter medicines with prolonged oral clearance used by the elderly in the Northern Region of England, with special regard to generic prescribing, dose form and sugars content.

As the longevity and population of elderly people has increased, the use of regular long-term medication for chronic medical problems has become more common. Medicines with prolonged oral clearance, for example syrups and chewable tablets, are commonly used in the elderly, many of whom retain their natural teeth into old age. These medicines may threaten dental health if they contain acidogenic sugars and are used long-term. As a part of an overall study of medication use in the elderly, three surveys were undertaken to assess the numbers of prescriptions and quantities of prescribed and 'over-the-counter' medicines with prolonged oral clearance dispensed during a 1 y period (1994), nationally and regionally. Of the 0.51 million litres of liquid oral medicines dispensed potentially for regular and long-term use by the elderly in the Northern Region in 1994, 94% was prescribed in primary care and 4% was sold over-the-counter from community pharmacies. When the effect of generic prescribing upon the sugars content of these medicines was considered, 96% of the volume of proprietary liquid oral medicines dispensed in primary care was sugars-free compared with 9% of generic liquid oral medicines. Of the 0.1 million litres of 'over-the-counter' liquid oral medicines sold in the Northern Region during 1994, 49% were sugars-free. In conclusion, although many prolonged oral clearance medicine preparations are sugars-free, due to generic prescribing a large proportion of the quantities dispensed for possible long-term use in the elderly are sugar-containing liquid oral medicines. In view of the increasing numbers of dentate elderly who require long-term medication, this is of some concern. The role of health professionals in raising awareness of the impact of generic prescribing on the sugars content of medicines is crucial if consumers are to benefit from the sugars-free option.