Editor(s)

Dr. Syed A. A. Rizvi
Professor,
Department of Pharmaceutical Sciences, Hampton University School of Pharmacy (HUSOP) Flemmie P. Kittrell Hall, 121 William R. Harvey Way, Hampton, VA 23668, USA.

ISBN 978-93-91595-56-2 (Print)
ISBN 978-93-91595-64-7 (eBook)
DOI: 10.9734/bpi/caprd/v1

This book covers key areas of Pharmaceutical Research and Development. The contributions by the authors include Acne vulgaris, allopathy, hyperkeratinizations, pilosebaceous gland, hyperseborrhoea and propionibacterium, Hypertension, cardiovascular disorders, red raspberry, cranberry, anthocyanins, ellagitannins, bioactive compounds, Erythrina variegate, MDA-MB-231, cytotoxicity, apoptosis, Rutin, cytotoxicity , High-Resolution Liquid chromatography Mass Spectrometry (HRLCMS), Cinnamomum Tamala and Spilanthes Acmella extract, antimicrobial evaluation, Phytochemical screening, lozenges, evaluation parameter, Heavy Metals, PAHs, Risk Assessment, Soft Drink, target hazard quotient (THQ), incremental lifetime cancer risk (ILCR), Lutein, ciprofloxacin, total RBCs count and total WBCs count, GABA  receptor, neuron disorders, abuse of alcohol, chronic effects of alcohol, benzodiazepines, ligand-gated ion channels (LGICs), Fexofenadine hydrochloride, montelukast sodium, HPLC, validation, simultaneous estimation, ICH guidelines, Multiple illnesses, drug reactions, remedial measures, Geriatrics, Visual illusions, rich afterimage illusion, eye movements, visual field constantcy, gaze direction, spatial vision, eye position, residual illusion, head tilt, proprioceptive signals, static retinal image, MRP2, miRNA133a, cyclosporine nephrotoxicity, proteinuric disease, FSGS, ET-BR ko-/-rats, Prostaglandins, arachidonic acid, differentiation inducers, differentiation therapy, wound healing, progenitor stem cells, chemo-surveillance. This book contains various materials suitable for students, researchers and academicians in the field of Pharmaceutical Research and Development.

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Chapters

Acne Vulgaris: A Brief Review

Current Aspects in Pharmaceutical Research and Development Vol. 1, 18 August 2021, Page 1-9
https://doi.org/10.9734/bpi/caprd/v1/3376F

The goal of this review is to look at the epidemiology, aetiology, pathophysiology, categorization, and therapy options for acne vulgaris. Acne is a multifactorial, polymorphic inflammatory condition of the pilosebaceous gland that manifests itself as skin lesions. It begins when a child reaches puberty. Interference in the sebaceous gland, which is linked to hyperseborrhoea, hormone dysregulation, microenvironment interconnection with neucleopeptide, variation in sebum fatty acid composition, follicular hyperkeratinizations, disfunction of innate and adaptive immunity, and induction of inflammation are all key mechanisms in the development of acneiform. The treatment of acne vulgaris is influenced by allopathic, ayurvedic, and homoeopathic medicine systems.

Role of Berries and Its Bioactive Compounds in Treating Hypertension: A Review

Ankita Wal, Pranay Wal, Tamsheel Fatima Roohi

Current Aspects in Pharmaceutical Research and Development Vol. 1, 18 August 2021, Page 10-29
https://doi.org/10.9734/bpi/caprd/v1/12344D

Study Objective: Hypertension or raised blood pressure leads to the occurrence of morbidity and mortality rate among peoples and it was considered as the primary factor for the occurrence of various cardiac and vascular disorders include ischemic cardiac disease, myocardial necrosis, cardiac failure, renal disorder, atherosclerosis, and cerebrovascular accident. Called “silent killer” because hypertension is an asymptomatic disease in the early stages with no indications on suffered patients and leads to act as a significant factor for the occurrence of severe other cardiovascular diseases (CVDs). As berries show considerable interest in improving cardiovascular diseases because they are rich in polyphenol contents and bioactive compounds. Besides their single usage, a polyherbal combination is much better for the treatment of hypertension.

Methods: The data were collected by reviewing a combination of research and review papers from different databases such as PubMed, Medline, ScienceDirect, and Web of science using search keywords such as “hypertension,” “cardiovascular disease,” “berries,” “cranberry,” and “red raspberry” with all their synonyms and related terms.

Results: Various studies shown better associations between higher berry flavonoids and other polyphenolic components and lower the risk of cardiovascular disorders. Based on various scientific evidence, the characteristic of various biochemical processes is treated by berries with its antioxidant, antihypertensive, and anti-sclerotic and other properties.

Conclusion: This paper concludes that in the present day, there is a global increase in berry consumption, which is used in the ailment of various cardiovascular diseases. The studies which are held are needed to define their optimal dose, process, or method of preparation (formulation) and the duration of berry intervention so that these showed better treatment options for hypertension. The literature strongly indicates that the herbs/plants show better efficacy as compared to allopathy and any other medication system.

Could Methanol Leaf Extracts of Erythrina variegata L. be a Potential Source of Anticancer Molecule against Breast Cancer Cell Lines? – A Preliminary in vitro Investigation

Vaishali Rai M., Vinitha Ramanath Pai, Samuel Kevin, Herga P. Kedilaya

Current Aspects in Pharmaceutical Research and Development Vol. 1, 18 August 2021, Page 30-44
https://doi.org/10.9734/bpi/caprd/v1/11654D

Introduction: In India, traditional/folklore medicine are known to use species of Erythrina variegata L. (E. variegata) in treatment of cancer. Hence the leaves of this plant could be explored for their anticancer potential.

Objectives: The objectives of the present study were, i) to evaluate the anticancer potential of crude extracts of the leaves of E. variegata with two solvents with different polarity, methanol and chloroform, ii) to explore the mechanism of cytotoxicity with the most effective extract, and iii) to identify the phytochemicals associated with the cytotoxicity of the most active extract.

Methods: The methanol soluble (EVM) and chloroform soluble (EVC) extracts of E. variegata were screened for cytotoxicity by [3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide] MTT assay with breast cancer cell lines - MCF-7 and MDA-MB-231. Further, the nucleoprotein content and cell morphology were studied with the EVM (more effective) treated MDA-MB-231 cells. The phytochemical composition of EVM was evaluated by High-Resolution Liquid chromatography Mass Spectrometry (HRLCMS).

Results: Among the two extracts, EVM was effective with a 50% Inhibitory concentration (IC50) of 92 µg/mL and 143 µg/mL on MCF-7 and MDA-MB-231 cells, respectively. The nucleoprotein content of EVM (IC50 143 µg/mL) treated MDA-MB-231 was 58.2% and the apoptotic index was calculated to be 51.8%. EVM treated MDA-MB-231 cells showed significant morphological changes suggestive of apoptosis. Phytochemicals such as rutin, podocarpatriene and cepharanthine were detected by HRLCMS which are reported to be cytotoxic.

Conclusion: The present study suggests that methanol extracts of the leaves of E. variegata could be a potential source of anticancer molecules.

Recent Formulation Development and Evaluation of Lozenges Containing Polyherbal Extract of Cinnamomum tamala and Spilanthes acmella

Pooja S. Dhoke, Dinesh M. Biyani, Avinash O. Maske, Milind Umekar, Bhushan Hatwar

Current Aspects in Pharmaceutical Research and Development Vol. 1, 18 August 2021, Page 45-54
https://doi.org/10.9734/bpi/caprd/v1/3953F

In recent years, the growing demand for herbal has resulted in a massive increase in the volume of plant material traded within and across the country. Tejpatta (Cinnamomum tamala) and Akarkara (Spilanthes acmella) are two major medicinal plants that are rich in therapeutic constituents. Cinnamomum tamala which is an evergreen tree up to 8 m in height is also cultivated. Spilanthus acmella is an annual hairy herb, up to 40-60 cm. tall with numerous stems of marigold yellow flowers.  The goal of this study is to develop a modern dosage form, such as lozenges, that is related with a long-term local cure that has a favourable therapeutic impact. The extracts of Cinnamomum tamala leaves and Spilanthes acmella flowers have antibacterial properties against the selected microorganism (staphylococcus aureus, Streptococcus mutans and Escherichia coli). The existence of various phytochemicals such as alkaloids, flavonoids, glycosides, and triterpenes was confirmed by qualitative phytochemical screening of ethanol, methanol, and petroleum ether extracts of Cinnamomum tamala leaves and Spilanthes acmella flowers extracts. The optimised formula F3 was chosen for the formulation of tablet lozenges and was manufactured by direct compression method, which exhibits optimal friability, weight uniformity, hardness, and disintegration time, according to the results obtained.

Study on Health Risk Assessment of Levels of Some Toxic Metals and Polycyclic Aromatic Hydrocarbons of Some Commercial Soft Drinks Commonly Consumed among Students of Nnamdi Azikiwe University, Awka, Anambra State, Nigeria

Rose Ngozi Asomugha, Chijoke Emmanuel Igwe, Peace Ukamaka Nome, Onyinye Mary Uchendu, Nwamkwere Godson

Current Aspects in Pharmaceutical Research and Development Vol. 1, 18 August 2021, Page 55-68
https://doi.org/10.9734/bpi/caprd/v1/3259F

Food Safety is of growing concern globally, and more so considering the relatively high proportion of soft drinks in the beverage market worldwide, and its rate of consumption especially amongst the youths. It is essential to evaluate the levels of toxic metals and Polycyclic Aromatic Hydrocarbons (PAHs) residues of which when present in soft drinks above the permissible limits could pose serious public health risk. The aim of this present study was to assess the levels of heavy metals (Pb, Hg, Cd ,As) and Polycyclic aromatic Hydrocarbons(PAHs) in 16 commercial soft drinks marketed in Awka, using Atomic Absorption Spectroscopy(AAS) and Flame Ionization detector (GC-FID), respectively. The objective of the study was to evaluate the potential human risk indices of heavy metals and polyaromatic hydrocarbons in the studied beverages. The carcinogenic and non-carcinogenic risk assessment were performed using the method established by United State Environmental Protection agency(USEPA).The data obtained were compared with the permissible limit set for drinking water by United State Environmental Protection Agency(USEPA),World Health Organization (WHO),Standard Organization of Nigeria(SON) and Federal Environmental Protection Agency(FEPA). The highest mean level of 0.6116 mg/l is related to Pb and the lowest of 0.0028mg/l related to Hg. The mean levels of the metals increased in this order: Hg<As<Cd<Pb. For the PAHs, using Benzo (a) pyrene as the benchmark for other PAHs congeners because of its strong carcinogenic potency, is not detected in this study, and thus pose no health risk. The target hazard quotient (THQ) of Hg in the studied samples is less than 1. Pb levels in75% the studied samples had THQ>1, and thus, pose a health risk. The hazard index, calculated as the combined risk of heavy metal toxicity is greater than unity (HI>1).The incremental lifetime cancer risk (ILCR) values estimated for Pb, As and Cd in the sample were 6.25%,31.25% and 25% ,respectively, rep- resenting higher than acceptable risk value of (10-6 -10-4) . The results raise a concern for the public exposed with respect to As and Cd carcinogenic risk values.

Determination of Possible Protective Effects of Lutein against Ciprofloxacin Induced Bone Marrow Toxicity in Rats

Alaa R. Khudhair, Nada N. Al-Shawi

Current Aspects in Pharmaceutical Research and Development Vol. 1, 18 August 2021, Page 69-77
https://doi.org/10.9734/bpi/caprd/v1/1860C

Ciprofloxacin, which is a second generation of fluoroquinolone and one of the most effective and widely used drugs within fluoroquinolone. Unfamiliar adverse effects of ciprofloxacin such as bone marrow (BM) suppression, thrombocytopenia, anemia, agranulocytosis, renal failure, and others observed. Lutein, is a xanthophyll (an oxygenated carotenoid), was focused by most studies as it has a strong antioxidant activity in vitro; and also, it has been associated with reducing the risk of the age-related disorders.

Study objectives was to describe the role of apoptosis through the measurement of Bcl-2 associated X protein (Bax) marker, as mechanisms of bone marrow toxicity induced by ciprofloxacin and to find whether lutein may have protective effects on ciprofloxacin-induced toxicity in bone marrow of rats.

Thirty six Sprague-Dawley rats were randomly divided into six groups (six animal each): Groups I (control), rats received single oral daily dose of liquid paraffin (4ml/kg) for 25 successive days by oral gavage; Group II, (ciprofloxacin-treated), received single oral daily dose of liquid paraffin (4ml/kg body weight/day) for 25 days, and subsequently received 500 mg/kg ciprofloxacin by oral gavage for the last 5 days; Groups III and IV, received oral dose of lutein (6mg/kg/day) and (24mg/kg/day), respectively by oral gavage for 25 successive days (lutein-treated); Groups V and VI, received oral dose of lutein (6mg and 24mg /kg/day), respectively by oral gavage for 25 successive days, and subsequently received 500 mg/kg ciprofloxacin orally for the last 5 days (lutein+ ciprofloxacin).

Ciprofloxacin (Group II) caused significant (P<0.05) reduction in total RBCs counts and -WBCs, and significantly elevations (P<0.05) Bcl-2 associated X protein (Bax) in bone marrow (BM) tissues homogenates compared to control (Group I) rats. Rats that orally received lutein (Groups III and IV), each produced non- significant differences (P>0.05) in total -RBCs and -WBCs and also produced non-significant differences (P>0.05) in Bax levels in BM tissues homogenates with respect to corresponding levels in Group I rats. Orally- administered lutein with ciprofloxacin (Groups V and VI), resulted in significant elevation (P<0.05) of total - RBCs and -WBCs, and significantly reduced (P<0.05) Bcl-2 associated X protein (Bax) in bone marrow (BM) tissues homogenates caused by ciprofloxacin compared to the corresponding levels in group of rats administered ciprofloxacin (Group II).

Results of the current research suggested that lutein may be a useful compound that alleviated ciprofloxacin-induced toxicity on bone marrow.

The Use Abusive of Alcohol and Benzodiazepines Induce Inhibitory Effect in the GABAA Neurotransmitter Implying to Neuron Disorders

Antônio José Rocha, Lara Lys Santos Rocha, Alice Soares de Queiroz, José Ednésio da Cruz Freire

Current Aspects in Pharmaceutical Research and Development Vol. 1, 18 August 2021, Page 78-85
https://doi.org/10.9734/bpi/caprd/v1/12603D

In this study aims to investigate the several changes that occur in central nervous system (CNS) receptor GABAA during consumption of drugs as benzodiazepines and alcohol Relevant research cited in literature were done between the abuses of alcohol and the GABAA receptor of the synaptic plasticity system implying to neuron disorders. These Findings in the literature specific reveals that although tolerance to alcohol intoxication probably occurs at multiple levels, alterations in synaptic functions are believed to play a major role. The compensatory changes in excitatory that alcohol inhibitory GABAA receptors probably contribute to the development of ethanol tolerance. These receptors are the sites of action of a number of drugs including barbiturates, benzodiazepines and anesthetics. The results revels several to neuron and peripheral tissues disorders caused by alcohol as well as, decreased flux of chloride ion in the channels of chore at the GABAA and GABAB receptors.

Development and Validation of Analytical Methods for Simultaneous Estimation of Some Drugs in Pharmaceutical Dosage Form

Current Aspects in Pharmaceutical Research and Development Vol. 1, 18 August 2021, Page 86-96
https://doi.org/10.9734/bpi/caprd/v1/13001D

For the simultaneous measurement of Fexofenadine hydrochloride (FEXO) and Montelukast sodium (MONTE) in combined tablet formulation, a new reversed-phase high performance liquid chromatography method was developed. Using 0.05 percent Orthophosphoric acid with a PH of 2.5 and a flow rate of 1 ml/min, efficient separation was obtained using a C18 Grace Column (4.6 250 mm, 5 um) as stationary phase with Methanol and H2O (70:30, v/v) as mobile phase.At 241.0 nm, the UV 730 D PDA detector was used for detection. Fexofenadine and Montelukast have a retention time of 6.0167 min and 8.500 min, respectively. The FEXO and MONTE were found to be linear throughout a range of60 $$\mu$$g/mL to 300 $$\mu$$g/mL and 5 $$\mu$$g/mL to 25 $$\mu$$g/mL , respectively. The developed method was precise, accurate, economic, quick, and selective. For drugs, the approach provides good resolution.FEXO & MONTE were separated using the aforesaid method with good peaks, minimal tailing, good retention time, and appropriate resolution time between peaks. As a result, this procedure was found to be appropriate and finalised.

Study on Geriatric Pharmacology: An Overview

Pooja Reddy, Devesh Gosavi, Sushil Kumar Varma

Current Aspects in Pharmaceutical Research and Development Vol. 1, 18 August 2021, Page 97-106
https://doi.org/10.9734/bpi/caprd/v1/10919D

Bioavailability of a drug depends on gastrointestinal absorption and the first pass metabolism in gastric mucosa and the liver. Elderly patients frequently experience multiple illnesses and take many drugs concurrently. The combination of altered drug activity, impaired homeostasis, and the use of multiple drugs by elderly patients results in frequent adverse drug reactions. Although they can be difficult to recognize in elderly patients, adverse drug reactions are a frequent cause of morbidity and may necessitate hospitalization. Because the risk of adverse drug reactions increases with the number of drugs taken, it is important to discontinue any treatment that is not efficacious. Adverse drug reactions are an important cause of morbidity and hospital admission in elderly patients5. 85 to 95% of ambulatory elderly take at least 1 medication, with an average of 3-4 per day. Bec ause of neurological, visual and auditory disabilities, elderly patients may have difficulty complying with complicated drug regimens. Some chronic diseases in elderly patients cannot be effectively treated with drugs. The survey studies regarding utilization of medicine as well as the education in elderly patients may reduce the morbidity in general. Furthermore, the education and the training of doctors for prescribing drugs in elderly patients in view of altered drug behavior in these patients in view of changed pharmacokinetic and pharmacodynamic behavior of the drugs will be remedial measures to decrease the morbidity of elderly patients to a greater extent.

The Rich Afterimage Illusions under Head-Image Tilting and the Internal Visual Space Model. A New Theoretical Comprehending

Gary M. Zenkin

Current Aspects in Pharmaceutical Research and Development Vol. 1, 18 August 2021, Page 107-127
https://doi.org/10.9734/bpi/caprd/v1/3985F

Some features of the illusions arising from the movement of the observer’s eyes and/or head under the background of the positive afterimage of the entire visual scene (rich afterimage-rAI) when the head and/or afterimage are tilted are described.

Under these conditions, there are the violations of the visual direction constancy and stability of not only the visual field but also near extrapersonal space. This happens also under the constant position of the eyes in orbits when changing of the fixation point by the head movements. The illusion of violation of the visual vertical on the background of an inclined rAI is also described. It turns out that the synthesis of the field of rAI does not depend on the state of eye vergence in a wide range.

The features of the so-called “residual illusion” are described in detail. In this phase all phenomena that have arisen against the background of rAI persist for tens of seconds in total darkness after the rAI is completely attenuated. This also applies to distorted perception of the visual vertical.

Based on the analysis of the rAI illusions and peculiar properties of the rich afterimage itself, it is proposed to consider the hypothesis, suggesting the complete nonparticipation of the efferent oculomotor subsystem signals in the mechanisms of the visual field constancy and the gaze direction constancy. The hypothesis suggests that the structurally rich visual scene allows the visual system to form a stable visual field and to calculate the observer’s gaze direction only based on the signals within the visual flow. The hypothesis allows to coherently interpret the main phenomena have been observed in the experiments. And the observation of an oblique 3-D rAI when the head is tilted to the shoulder clearly indicates that not the images on the retinas, but the internal visual space (IVS) model is the object of vision.

Cyclosporine A Nephrotoxicity: Downregulation of Multiple Drug Resistance-Associated Protein 2 (MRP2) by Upregulated miRNA133a: Its Importance in Renal Transplantation and Treatment of Proteinuric Disease Such as FSGS

Sandra Stefanikova, Joe Schankin, Melanie von Brandenstein, Reinhard Büttner, Heike Goebel, Jochen W. U. Fries

Current Aspects in Pharmaceutical Research and Development Vol. 1, 18 August 2021, Page 128-157
https://doi.org/10.9734/bpi/caprd/v1/3981F

Background: Multiple drug resistance-associated protein 2 (MRP2) is regarded as transport protein for xenobiotics such as cyclosporine A (CyA). We have shown that MRP2 is downregulated though miRNA133a binding to its 3`UTR region, induced by endothelin-1 (ET-1) via the ETB-receptor in minimal change nephrosis (MCN) and membranous nephropathy (MN). The status in focal-segmental sclerosis, (FSGS) where CyA is a treatment option, is still unknown. The mechanism of CyA nephrotoxicity in renal transplantation is also still elusive. In particular, co-morbidities/clinical parameters, the morphological extent of MR2 damage and the involvement of miRNA133a leading to nephrotoxicity have not been investigated.

Aims: To analyze co-morbidities, the role of ET- 1 and miRNA133a for development of CyA renal toxicity and in FSGS.

Methods: Analysis of co-morbidities/clinical factors in 230 biopsies from 124 patients. In 35 CyA patients (tubular damage, arteriolar damage, no damage; plus 5 cases of so- called null biopsies as controls), and in FSGS (n=8) immune histology and subsequent morphometry of MRP2 expression was performed and a qRT-PCR for the detection of miRNA133a was analysed. Human proximal tubular cell culture was used for studying the effect of ET-1 alone or in combination with CyA on MRP2 and miRNA133a levels. MiRNA levels were further determined in the ETB-receptor knock-out rat (ETBR sl/sl; wt vs. ko -/- ETBR) after 5/6 nephrectomy as a model for FSGS.

Results: No single clinical parameter was clearly responsible for CyA nephrotoxicity. Morphometric analysis revealed an increasing degree of damage: from no CyA toxicity, to arteriolar CyA toxicicity, to combined arteriolar and tubular toxicity; the maximum degree was seen in tubular toxicity. The effect could be studied in human proximal tubular cell culture, where the combination of ET-1 and CyA showed a higher effect of tubular damage than ET- alone. CyA induced mostly tubular but also arteriolar damage by downregulating the mrp2 gene via the upregulation of miRNA133a. In FSGS, with only a small difference to normal conditions observed by immune histology, by qRT-PCR Mrp2 was downregulated, while miRNA133a was clearly upregulated. Under proteinuric conditions of renal ablation, ET-BR knock-out animals were protected from miRNA133a upregulation.

Conclusion: Downregulation of MRP2 by miRNA133a is an important mechanism of CyA nephrotoxicity and in FSGS. The intensity of cytotoxicity may increase if FSGS is treated with CyA. Potential urinary analysis as detection assay and treatment options by an ETB-receptor antagonist are discussed. The therapeutic potential in steroid resistant syndrome such as in African pediatric FSGS cases is outlined.

Arachidonic Acid and Its Metabolites as Differentiation Inducers for the Perfection of Wound Healing to Avoid Cancer and to Beat Cancer

Ming C. Liau, Jai-Hyun Kim, John P. Fruehauf

Current Aspects in Pharmaceutical Research and Development Vol. 1, 18 August 2021, Page 158-167
https://doi.org/10.9734/bpi/caprd/v1/12997D

The objective of this study is to explore the role of arachidonic acid and its metabolites in wound healing, cancer evolution, and cancer therapy. Cell Differentiation Agent-2 (CDA-2) was a promising hypomethylation agent approved by the Chinese FDA for the therapy of Myelo Dysplastic Syndrome (MDS). MDS is a disease attributable entirely to Cancer Stem Cells (CSCs). A drug effective for the therapy of MDS means that drug can also be effective for the eradication of CSCs. The active components of CDA- 2 are Differentiation Inducers (DIs) and Differentiation Helper Inducers (DHIs). DIs are chemicals capable of eliminating telomerase from abnormal Methylation Enzymes (MEs) found in human cancers and primitive stem cells such as Progenitor Stem Cells (PSCs) and Embryonic Stem Cells (ESCs). The major DIs of CDA-2 were organic acids without UV absorption. Without UV absorption as a guide, it was difficult to purify DIs of CDA-2 for identification. Thus, we pursued possible candidates to function as DIs. We were interested in Prosta Glandin E2 (PGE2) since it was linked to wound healing, which is a major biological function of PSCs and CSCs. CSC eradication has been a significant goal of our research. PGE2 was found in the previous study effective as a DI, which encouraged us to look into other PGs to function as DIs with better activity and stability, and less adverse side effects. PGJ2 and 16, 16-dimethylPGE2 were the two PGs, good as DIs for the development of CDA formulations. PGJ2 was active in the dosage ranges between 4 and 17 $$\mu$$M with a maximum to induce 86% NBT+cells at 17 $$\mu$$M. 16, 16-dimethylPGE2 was active in the dosage ranges between 10 and 32 $$\mu$$M with a maximum to induce 83% NBT+cells at 27 $$\mu$$M. DI activities of bicycloPGE2 and Arachidonic Acid (AA) were very close. Both were modestly active between 20 and 42 $$\mu$$M with a maximum of 42%-52% NBT+cells at 42 $$\mu$$M. Although AA is not very active as a DI, the strong synergistic potentiation of DI activity by pregnenolone can boost its usefulness as an effective DI. Our previous studies indicated that the DIs of CDA-2 were either in liposomal complexes with pregnenolone or in association with cell membrane fragments. AA may very well be a major DI of CDA-2. As a result, AA could be a useful surveillance DI for preventing cancer in healthy persons. This research also indicates that metabolites involved in wound healing are also involved in chemo-surveillance.