Using Umbilical Cord Tissue to Identify Prenatal Exposure to Fentanyl and Other Commonly Abused Drugs

Background: Prenatal exposure to fentanyl may lead to Neonatal Abstinence Syndrome (NAS), a constellation of symptoms observed when newborns begin withdrawing from addictive substances such as opioids. The use of umbilical cord tissue segments (UC) for newborn toxicology has been increasing due to its apparent long detection window, sensitivity, and ease of collection. However, very little has been reported in the literature concerning the prevalence of in utero exposure to fentanyl and co-exposure with other commonly abused substances. Specific aim: The specific aims of this retrospective study are twofold. We will report prevalence of neonatal exposure to fentanyl for a nationwide high-risk population using UC submitted to a national reference laboratory for routine forensic toxicology analysis and the co-exposure patterns observed for these fentanyl-exposed neonates. Methods: A secondary analysis was performed using historical data for UC received between January 1, 2020 and December 31, 2020 for routine forensic toxicology analysis. Results: During the study period, our laboratory received 23,104 UC for analysis and 9667 (41.8%) of those UC were positive for at least one drug. The prevalence of fentanyl detection was 1.9% (n = 429). Of these 429 specimens there were 407 UC where both fentanyl and norfentanyl were detected. There were 14 UC where only fentanyl was detected and 8 UC where only norfentanyl was detected. When detected, the median concentrations of fentanyl and norfentanyl were 4029 pg/g (IQR: 1696, 9230 pg/g) and 10,756 pg/mg (IQR: 3925, 25,288 pg/g), respectively. Of the 429 positive fentanyl and/or norfentanyl UC, 33 (7.7%) were only positive for fentanyl and/or norfentanyl. Of the 396 polypositive UC, morphine was the highest co-exposure with 243 UC (56.6%) being positive for both fentanyls and morphine. The second most prevalent co-exposure observed was methamphetamine/amphetamine (n = 173;40.3%) followed by cannabinoids (n = 113;26.3%) and benzoylecgonine (cocaine metabolite;n = 106;24.7%). Conclusions: Nonmedical use of fentanyl is an alarming trend in this country including this maternal demographic reported here. Fentanyl was typically found with other commonly abused substances.

A Comparison of Turnaround-Times for Two Popular Specimen Types Used for Newborn Toxicology: Meconium and Umbilical Cord Tissue

Background: Prenatal exposure to illicit substances is responsible for several long-term negative health consequences. It is critical for healthcare professionals to know the extent and scope of prenatal substance exposure in their cases. Several studies exist with mixed results comparing the effectiveness of umbilical cord tissue (UCT) and meconium (MEC) as toxicology specimen types. The specific aim of this study is to compare the use of UCT and MEC regarding the time interval between the birth of the neonate, receipt of the specimen at the laboratory, and the hospital’s receipt of the final toxicology report. Method: The study queried de-identified results of 5358 consecutive UCT and 706 MEC from our laboratory. Results: The mean time from birth to receipt of the specimen at the laboratory for MEC and UCT was 4.5 days ± 2.9 days and 2.8 days ± 1.9 days, respectively. The mean time from birth to final report for MEC was 6.9 days ± 3.8 days, 5.7 days ± 3.3 days, and 8.4 days ± 3.8 days for all MEC specimens, negative MEC, and positive MEC, respectively. The mean time from birth to final report for UCT was 4.3 days ± 2.4 days, 3.5 days ± 2.2 days, and 5.4 days ± 2.2 days for all UCT, negative UCT and positive UCT, respectively. Discussion/Conclusion: Receipt of drug test results of the neonate prior to release from the hospital is critical. This study shows that UCT offers an advantage when results are needed quickly to make informed decisions about the health and well-being of newborns.

Plants Used as Antihypertensive

Hypertension is a critical health problem and worse other cardiovascular diseases.It is mainly of two types:Primary or essential hypertension and Secondary hypertension.Hypertension is the primary possibility feature for coronary heart disease,stroke and renal vascular disease.Herbal medicines have been used for millions of years for the management and treatment of hypertension with minimum side effects.Over aim to write this review is to collect information on the anti-hypertensive effects of natural herbs in animal studies and human involvement as well as to recapitulate the underlying mechanisms,from the bottom of cell culture and ex-vivo tissue data.According to WHO,natural herbs/shrubs are widely used in increasing order to treat almost all the ailments of the human body.Plants are the regular industrial units for the invention of chemical constituents,they used as immunity booster to enhance the natural capacity of the body to fight against different health prob-lems as well as herbal medicines and food products also.Eighty percent population of the world(around 5.6 billion people)consume medicines from natural plants for major health concerns.This review provides a bird’s eye analysis primarily on the traditional utilization,phytochemical constituents and pharmacological values of medicinal herbs used to normalize hypertension i.e.Hibiscus sabdariffa,Allium sativum,Andrographis paniculata,Apium graveolens,Bidenspilosa,Camel-lia sinensis,Coptis chinensis,Coriandrum sativum,Crataegus spp.,Crocus sativus,Cymbopogon citrates,Nigella sativa,Panax ginseng,Salviaemiltiorrhizae,Zingiber officinale,Tribulus terrestris,Rauwolfiaserpentina,Terminalia arjuna etc.

Anti-oxidant and anti-inflammatory activity of leaf extracts and fractions of Mangifera indica

Objective:To evaluate the anti-oxidani and anti-inflammatory activity of leaf extracts and fractions of Mangifera indica in in vitro conditions.Methods:In vitro DPPH radical scavenging activity and lipoxygenase（LOX） inhibition assays were used to evaluate the anti-oxidant and anti-inflammatory activities respectively.Methanolic extract（MEMI）,successive water extract （SWMI） and ethyl acetate fraction（EMEMI）,n-butanol fraction（BMEMI） and water soluble fraction （WMEMI） of methanolic extract were evaluated along with respective reference standards. Results:In in ritro DPPH radical scavenging activity,the MEMI,EMEMI and BMEMI have offered significant antioxidant activity with IC50 values of 13.37.3.55 and 14.19μig/mL respectively.Gallic acid,a reference standard showed significant antioxidant activity with IC? value of 1.88 and found to be more potent compared to all the extracts and fractions.In m vitro LOX inhibition assay,the MEMI,EMEMI and BMEMI have showed significant inhibition of LOX enzyme activity with IC50 values of 96.71.63.21 and 107.44μg/mL respectively.While,reference drug Indometlhacin also offered significant inhibtion against LOX enzyme activity with IC50 of 57.75.Furthermore,MEMI was found to more potent than SWMI and among the fractions EMEMI was found to possess more potent antioxidant and anti-inflammatory activity.Conclusions:These findings suggest that the MEMI and F.MEMT possess potent anti-oxidani and anti-inflammatory activities in in vitro conditions.

Neonatal Cord Tox Panel and Maternal Perinatal Fentanyl Exposure: A Retrospective Chart Review

Objective: The specific aim of this study was to determine if the currently available cutoff for fentanyl in umbilical cord (UC) was appropriate to distinguish illicit fentanyl exposure from therapeutic in-hospital administration of fentanyl. Study Design: Medical record review was conducted for perinatal administration of fentanyl and the detection of fentanyl in the corresponding routine UC toxicology. Specimens were initially tested with immunoassay followed by mass spectrometry (n = 62). Result: Excluding a single specimen that was confirmed positive, specimens were below the assays’ limit of quantification. The immunoassay’s mean b/b0 for the cases that received and did not receive fentanyl prior to delivery was 91.3% ± 10.6% and 98.2% ± 6.5%, respectively (p = 0.003). Conclusion: We demonstrated that UC is a suitable specimen type for the detection of fentanyl and that the cutoff selected adequately identifies illicit fentanyl use while not flagging cases where fentanyl was administered by the hospital prior to birth.

The Detection of 1-Palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphoethanol and Ethyl Glucuronide in Human Umbilical Cord

In utero exposure to ethanol continues to be a significant public health issue and neonatal healthcare professionals are in need of objective means to identify exposed newborns. The aim of this study was to fully validate two methods for the detection of two direct alcohol biomarkers, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanol (POPE) and ethyl glucuronide (EtG), in umbilical cord and apply the assays to a group of authentic specimens. The limits of detections were 2 and 1 ng/g for POPE and ETG and the limits of quantitation were 4 and 3 ng/g, respectively. Inter and intra-day precision and accuracy measurements were within 15%. The assays were applied to 308 authentic specimens where we detected POPE in five (1.6%) specimens and EtG in twelve (3.9%) specimens. The mean concentrations were 11.4 ng/g ± 9.4 ng/g and 127.2 ± 227.7 ng/g for POPE and EtG, respectively. This study suggested that umbilical cord was a suitable specimen type for the identification of newborns exposed to ethanol in the womb and the prevalence of POPE and EtG detected in umbilical cord were consistent with the prevalence of self-reported binge drinking reported by the National Birth Defect Prevention Study (NBDPS) and Behavioral Risk Factor Surveillance System (BRFSS). Further studies are required to fully describe the association between the observed concentrations of POPE and EtG in umbilical cord to the level of maternal consumption of ethanol.

Development and Validation of a Method for Simultaneous Determination of Metformin Hydrochloride and Sitagliptin Phosphate in a Formulation by RP-HPLC

Present study was aimed to develop and validate a reverse-phase high-performance liquid chromatography method for simultaneous determination of sitagliptin phosphate and metformin hy-drochloride in a marketed formulation. The drug separation was performed on Hibar-240, Li-chrosphere-100 C18 ODS (250 × 4.6 mm, 5 μm) column, at a flow rate of 1 mL/min. The mobile phase used was a mixture of methanol: potassium di-hydrogen phosphate buffer at a ratio of 70:30 v/v. The detection was carried out at a wavelength of 266 nm. The retention times of sitagliptin phosphate and metformin hydrochloride were found as 6.1 and 4.9 min respectively. Linear calibration curves with good correlation coefficients were obtained over the concentration ranges of 10 - 50 μg/mL for sitagliptin and 20 - 100 μg/mL for metformin. The limit of detection was 0.016 and 0.14 μg/mL and the limit of quantification was 0.048 and 0.42 μg/mL for sitagliptin phosphate and metformin hydrochloride respectively. Validation of the method demonstrated system selectivity, specificity, linearity, accuracy and precision. The developed method was found useful in the simultaneous analysis of sitagliptin phosphate and metformin hydrochloride in formulation.

The Detection of THCA Using 2-Dimensional Gas Chromatography-Tandem Mass Spectrometry in Human Fingernail Clippings: Method Validation and Comparison with Head Hair

Marijuana use as well as abuse is a significant public health and public safety concern in the United States and using hair to identify marijuana users and abusers has been gaining acceptance in a number of venues including workplace, court ordered, and substance abuse treatment monitoring. After the presentation of a fully validated 2-dimensional gas chromatography-tandem mass spectrometry method for the detection of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCA), the chief metabolite of the main psychoactive compound in marijuana, Δ9-tetrahydrocannabinol (THC), we evaluated the usefulness of fingernail clippings as an alternative specimen type to hair by the analysis of a set of 60 matched pairs of head hair and fingernail clippings. The limit of detection was 10 fg/mg, the limit of quantitation was 20 fg/mg, and the assay was linear from 20 fg/mg to 500 fg/mg. The intra- and inter-assay imprecision and bias studies at 4 different concentrations (50, 100, 500, and 1000 fg/mg) were acceptable where all % Target observations were within 16% of their expected concentrations and all %CV calculations were less than 13.5%. THCA was detectable in more fingernail specimens (53.3%) than hair specimens (46.7%) and the mean concentrations in nails were on average 4.9 times higher than in hair (1813 fg/mg and 364 fg/mg, respectively). The THCA concentrations in hair and nail were strongly associated (r = 0.974, P < 0.01, n = 60) and the association was significant. The study demonstrated that fingernail clippings are a suitable alternative specimen type to hair to monitor for marijuana use and abuse.

Long-Term Detection of Propofol Glucuronide in Urine Following Anesthetic Induction and Maintenance with Propofol

Propofol is the most commonly used compound for the intravenous induction and maintenance of anesthesia. Propofol addiction and abuse have become causes for concern in the healthcare community, especially among anesthesia and surgical professionals. The US Drug Enforcement Administration does not list propofol on any Schedules and most hospitals do not have inventory controls in place to prevent its misuse. Propofol is detectable in blood plasma as the parent compound for as much as 15 hours post-anesthesia. The metabolite propofol glucuronide (PPFG) has been detected in blood and urine as far out as 60 hours. Here we report the long-term renal excretion of PPFG in specimens from A) four participants following a 14-day course of orally ingested propofol dosing, and B) a female patient following anesthetic induction and 15 minutes’ maintenance with propofol. Urinary PPFG was measurable well above limits of quantitation up to 6 days following oral ingestion and 28 days post-anesthesia. We also present a third set of data evaluating the likelihood of passive exposure to aerosolized propofol in the surgical environment by analyzing the levels of urinary PPFG of healthcare workers following operating room work shifts. The results presented here demonstrate that quantitation of PPFG in urinary samples is an efficient method of long-term screening for propofol misuse and abuse.

Development and Validation of a Method for Simultaneous Determination of Metformin and Saxagliptin in a Formulation by RP-HPLC

A simple, specific, sensitive, precise and accurate reverse phase high performance liquid chromatographic method (RP-HPLC) was developed for the simultaneous analysis of Metformin and Saxagliptin in active pharmaceutical ingredients (APIs) as well as in marketed tablet (combination) dosage forms. The method was achieved on Enable C18 G (250 × 4.6 mm;5 μm particle size) column using 0.05 M KH2PO4 buffer (pH 4.5):Methanol:Acetonitrile (60:20:20 %v/v) as a mobile phase at a flow rate of 0.6 mL/min and by employing UV detection at 220 nm wavelength. The retention time of Metformin and Saxagliptin were found to be 4.38 min and 6.92 min, respectively. The method was validated as per ICH guidelines. The limit of detection (LOD) and limit of quantification (LOQ) of Metformin were found to be 0.112 μg/mL and 0.373 μg/mL, respectively, while those of Saxagliptin were found to be 0.029 μg/mL and 0.096 μg/mL, respectively. The method was found to be rapid, sensitive, linear, specific, accurate, precise and economic for the quality control and stability assays of Metformin and Saxagliptin in marketed tablet dosage forms.

The Identification of Prenatal Exposure to Mitragynine Using Umbilical Cord Tissue

Objective: Kratom is widely available and literature exploring the effects of prenatal kratom exposure is lacking. This study aims to report a validated method for the detection of mitragynine in the umbilical cord and report our observations for specimens received at a national commercial reference laboratory. Study Design: Assays were validated according to the recommendations of ANSI/ASB. A retrospective evaluation of records at a national reference laboratory was conducted to determine prevalence and co-exposure to other substances of abuse. Result: Mitragynine was detected in 19 of 4456 specimens (0.43%) with concentrations ranging from 4 to >50 ng/g. Thirteen (13) of these specimens were positive for only mitragynine while the other 6 were also positive for either marijuana or opiates. Conclusion: Umbilical cord is a suitable specimen type for the surveillance of maternal kratom use and can be used to identify exposed neonates for further investigations into short- or long- term health consequences.

Concept of dushi visha(latent poison)a review in ayurveda

A poison,which is having fewer properties,which means less thanit’s own ten classical properties or the poison which is having lesser potency of all ten properties,attains a accumulative or hidden stage in the body is called Dushi Visha(latent poison).Low potency of all the ten qualities of poison are said to be responsible for the delayed action and cumulative toxicity on the body.A much detailed description about DushiVisha is not seen in Ayurvedic classics.The concept of DushiVisha is still an enigma.To understand Dushi Visha,it is important to understand that what are theoriginating factors can be considered under DushiVisha,how it remains in the body without undergoing elimination,how does it causes cumulative toxicity,which factors will aggravate DushiVisha,how the clinical features of DushiVisha will be presented in the body.To get proper answer to all these practical queries,it is necessary to go through it’spathology.Here an attempt is made to review the concept of DushiVisha in detail.

Applied aspect of ayurvedic fumigation (Dhupana Karma) in epidemic era: a conceptual review

Ayurveda has attached great importance to preventive medicine and has described several methods for disinfection.Today we are living in a world where we are constantly facing new diseases and surrounded by various types of pathogenic microorganisms in our daily lives,which make us their prey as soon as they get a chance.Some of these microorganisms are the ones that give rise to terrible types of infectious diseases,which have the potential to influence a large section of the population.The Epidemic is the occurrence of more cases of a disease than would be expected in a community or region during a time of period,a severe outbreak of a disease such as SARS.Epidemiological diseases have been described in Ayurveda regarding Janpadodhwansa.Vayu(Air),Desha(Land),Kala(Season),and Jala(Water)are the four factors that are contaminated during the epidemic,according to Ayurveda.Dhupana(fumigation)is the act by which considerable success can be achieved in the field of disinfecting contaminated air and surface.Therefore,because of the present circumstances,this article is an attempt by which to show the importance of Dhupana Karma(fumigation)for the process of disinfection.

Cancer treatment with biosimilar drugs:A review

Biosimilars are biological drugs created from living organisms or that contain living components.They share an identical amino-acid sequence and immunogenicity.These drugs are considered to be cost-effective and are utilized in the treatment of cancer and other endocrine disorders.The primary aim of biosimilars is to predict biosimilarity,efficacy,and treatment costs;they are approved by the Food and Drug Administration(FDA)and have no clinical implications.They involve analytical studies to understand the similarities and dissimilarities.A biosimilar manufacturer sets up FDA-approved reference products to evaluate biosimilarity.The contribution of next-generation sequencing is evolving to study the organ tumor and its progression with its impactful therapeutic approach on cancer patients to showcase and target rare mutations.The study shall help to understand the future perspectives of biosimilars for use in gastro-entero-logic diseases,colorectal cancer,and thyroid cancer.They also help target specific organs with essential mutational categories and drug prototypes in clinical practices with blood and liquid biopsy,cell treatment,gene therapy,recombinant therapeutic proteins,and personalized medications.Biosimilar derivatives such as monoclonal antibodies like trastuzumab and rituximab are common drugs used in cancer therapy.Escherichia coli produces more than six antibodies or antibody-derived proteins to treat cancer such as filgrastim,epoetin alfa,and so on.

Pharmacognostic and phytochemical studies as an invaluable approach for correct identification of medicinal plants:The case of Artemisia vulgaris L.substituted for Artemisia annua L.in Western Uganda

Background:Different parts of Artemisia vulgaris L.(A.vulgaris)are ethno-medicinally used as an emmenagogue and for the treatment of ailments such as malaria fever,ulcers,and cancer.However,anecdotal evidence shows that the plant is often substituted for Artemisia annua L.(A.annua)by herbalists in Western Uganda due to similarities in their morphology.Misidentification of medicinal plants and mislabelling of herbal products have been incriminated in toxicity and adverse health outcomes in traditional medicine practise.Because safety continues to be a major issue with the use of herbal remedies,it becomes imperative therefore that medicinal plants should be correctly identified.Methods:This study focused on investigating the macroscopic,microscopic,physicochemical characteristics and phytochemical composition of A.vulgaris leaves compared to A.annua to ease its correct identification.Results:The results showed that there are some colour differences between the leaves of the two species,with a close arrangement of microscopic features but different leaf constants.The leaves of the two Artemisia species had similar tastes,but their shapes and colours(greenish-yellow for A.annua and dark green for A.vulgaris)can be used by the local community to distinguish between them.The artemisinin content was higher in A.vulgaris leaves(1.72%)than in A.annua(1.43%),but the reverse was observed for the total flavonoid content.Conclusion:This observation could justify the change in the use of A.vulgaris by the indigenous community in western Uganda.Further studies should consider the pharmacognostic comparison of A.annua with other species in the genus Artemisia and the use of molecular techniques such as DNA barcoding.

Targeting colorectal cancer using dietary flavonols

Colorectal cancer is among the well-known forms of cancer and a prominent cause of cancer demises worldwide.In vitro experiments reinforced by animal studies,as well as epidemiological studies of human colorectal cancer propose that the growth of this disease can be moderated by eating aspects.Dietary intake including green vegetables and fruits may result in the reduction of colon cancer chances.The finding suggests that the combinations of dietary nutrients may deliver additive or synergistic effects and might be a powerful method to avoid or eradicate colon cancer beginning and/or development.Flavonols are one of the most widespread dietary nutrients of the polyphenols-flavonoids and major constituent of Allium and Brassicaceae vegetables.Flavonols present in vegetables of Allium and Brassicaceae family are kaempferol,myricetin,quercetin,and isorhamnetin.These flavonols are claimed to have antiproliferative activity in vivo and in vitro against colorectal cancer.The objective of this review is to summarize the role of flavonols obtained from dietary sources in the prevention and treatment of colorectal cancer.

Plants’Steroidal Saponins‑A Review on Its Pharmacology Properties and Analytical Techniques

The plant is a rich repository of useful secondary metabolites with profound medicinal potential.Saponins,one type of bioactive compound,are amphitheatric glycosides with one and more hydrophilic sugar and hydrophobic steroidal and terpenoid part.The former is known as steroidal saponin,and the latter is called terpenoid saponins.Steroidal saponin is mostly distributed among monocotyledon families such as Asparagaceae,Amaryllidaceae,Dioscoreaceae,Smilacaceae,and Liliaceae.Even though it is unusual,it could also be detected to some extent by dicotyledonous angiosperms,such as Plantaginaceae,Zygophyllaceae,Fabaceae,Asteraceae,and Solanaceae.It exhibits diverse pharmacological ability including antimicrobic,anti‑inflammatory,cAMP phosphodiesterase inhibitory,antiadipogenic,bactericide,cardioprotective,antitumor,antidiabetic,cytotoxic activity,antifungal,antiviral,antioxidant,and hepatoprotective.Steroidal saponin timosaponin AIII from Anemarrhena asphodeloides has been found to possess antitumor activity.Diosgenin,another steroidal sapogenin,has the potential of preventing neurological diseases by affecting different signaling pathways,increasing bone formation,and increasing antithrombotic activity.Spicatoside A from Liriope platyphylla possesses anti‑inflammatory,antiasthma,and antiosteoclastogenic activities.TTB2 from Trillium tschonoskii exhibits anticancer potential.The cell cycle arrest and ROS‑dependent autophagy are induced by polyphyllin I.These diverse biological activities of steroidal saponins are attributed to the variability of their structural features.Analysis of steroidal saponins in plant materials mainly utilizes classically and advances thin layer chromatography(TLC)on normal and reverses‑phase(high‑performance thin‑layer chromatography,densitometric TLC),gas chromatography,LC,UPLC,ultra‑high‑performance liquid chromatography(HPLC),supercritical fluid chromatography,and HPLC coupled to ultraviolet detector and diode array detector.HPLC coupled with MS and Nuclear magnetic resonance is used for online identification of separated saponins.The present review aims to furnish a comprehensive account of the recent advances in analytical methods of determination and medicinal applications of steroidal saponins.

Role of semi-purified andrographolide from Andrographis paniculata extract as nano-phytovesicular carrier for enhancing oral absorption and hypoglycemic activity

Objective:Andrographis paniculata is a well-known medicinal plant in Southeast Asia,India and China.The plant contains andrographolide(AN),a very important phytochemical used in various health problems.However,AN is low in oral absorption bioavailability of AN due to the rapid clearance and high protein binding capacity.Methods:The present study was aimed to develop a nano-phytovesicular formulation of semi-purified AN extracts from a naturally occurring phospholipid(soya phosphatidylcholine)in order to increase the oral absorption and antihyperglycemic activity in rats.Results:The nano-phyto vesicle of semi-purified AN extracts equivalent to 25 mg/kg AN significantly protected the hyperglycemic condition of rats.The in vitro and in vivo experiments results proved that the nano-phytovesicular system of plant extracts containing AN produced better oral absorption,bioavailability and improved antihyperglycemic activity compared with that of free AN at dose of 50 mg/kg.Conclusion:Hence,the prepared semi-purified extract nano-phytovesicular system is helpful in solving the problem of rapid clearance of AN.