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Dear Reader, Government of India is currently negotiating a limited trade deal with USA which is likely to be signed after the US elections. Although, the current negotiations do not cover the Intellectual Properties (IP) or Pharmaceuticals, a limited deal if concluded successfully is expected to be followed by a full Trade Deal (FTA), which will include IP and Pharmaceuticals too. In spite of all the negative (or positive?) consequences of COVID-19, the Sars2CoV virus has provided humanity with a great learning experience. Repurposing of known drugs, bio-natural products, biologicals and vaccines such as TB, Leprosy, BCG have all been undertaken in the desperate search for prophylactic, therapeutic as well as preventive options. However it is interesting to note and appreciate that except for pre-existing patent rights (ex:-Remdesivir), there have hardly been any emphases on protecting the Covid remedies through patenting.

Repurposing of drugs was most often a strategic approach, though by “serendipity” in few instances. Early practice of pharmacovigilance in USA, led to near ‘serendipitous’ addition to market value for many “first use” drugs. Glaxo-Welcome’s Bupropion brand “Wellbutrin” was first approved for treatment of depression. While “Wellbutrin” received an average response in the anti-depression segment, pharmacovigilance reports to FDA was perplexing. Patients gave conflicting response. While a few wanted to change to another drug, many others wanted to continue the use of the prescribed drug even after being advised to stop. The reason when investigated, was that the patients felt the urge to discontinue smoking, which was acceptable to some, while not to others. When this finding was received by the FDA from multiple specialists, Glaxo-Welcome was asked to conduct a full study on a priority basis. Consequently, FDA granted a fast track approval for use of Bupropion for smoking cessation. Antidepressant “Wellbutrin” opened up new pathway for smokers to “kick the Butts” through its second use “Avatar”, in form of “Zyban” for smoking cessation and become the first global breakthrough drug of choice for this second use. Pharmacovigilance helps in developing a road map for secondary use.

More than 100 years before India was recognised as the “Generic Capital” or “Pharmacy of the World, India was acclaimed for the “Materia Medica” and the extensive research on natural products by Sir Col. Dr. Ram Nath Chopra, the father of Indian Pharmacology. In fact, Dr. M.L. Shroff got inspired from Sir R.N. Chopra and started the first Pharmacy course at Banaras Hindu University in 1932. Every student (even veterans) of Pharmacy should know that Drugs Act, 1940 (later renamed as Drugs and Cosmetics Act) as well as formal courses in Ayurveda, Siddha and Unani were started under his mentorship. DTAB (Drugs Technical Advisory Committee) was set up under his stewardship. The first edition of the Indian Pharmacopoeia (evolved from Indian pharmacopoeial list 1946) 1955 was published with his contributions. “We are reaping the fruits of the plant grown by their sown seeds. We should make the same available to our future generations” said the biographer, Roja Rani. Prof.Harkishan Singh in J.Young Pharm, 2009 (Vol.1/No.3) had profiled Dr.R.N. Chopra (which is reproduced herein). Later Dr. K.M. Nadkarni came out with “Indian Materia Medica” in two volumes in 1908 with Foreword by Dr. R.N. Chopra. These are extremely valuable reference books for further research in Indian Natural Products.

Background: Awake fiberoptic intubation (AFOI) is usually the primary method for airway management in patients with anticipated difficult airway. To achieve optimal conditions for AFOI, the pharmacological agents chosen for sedation should be short acting and have little suppression of spontaneous ventilation. Aims and Objectives: The aim of this study was to compare the efficacy between dexmedetomidine and fentanyl for conscious sedation in AFOI. The objectives were to assess the intubating conditions, intubation attempts, and the hemodynamic responses between the groups receiving the two drugs. Materials and Methods: This prospective randomized double-blind study was done in 40 patients of the American Society of Anesthesiologists physical statuses I, II, and III, aged between 20 and 65 years. One group received fentanyl 2 mcg/kg infusion over 10 min. The other group received dexmedetomidine 1 mcg/kg infusion over 10 min. AFOI was done in both groups when patients achieved Ramsay sedation score of three. Time to sedation and time to intubation were noted. Intubating conditions were assessed with cough score. Heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and oxygen saturation were also monitored for 30 min with 3 min interval after starting the drug infusion. The number of intubation attempts was also noted. Results: We found that the time to sedation and the time to intubation were shorter with dexmedetomidine than with fentanyl. There were no significant differences in cough score, number of intubation attempts, heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and oxygen saturation between the groups. Conclusion: Both dexmedetomidine and fentanyl can be used to achieve adequate sedation for AFOI along with regional block and topical anesthesia. However, dexmedetomidine achieved target sedation faster compared to fentanyl enabling early intubation.

Background: Propofol is a commonly used intravenous anesthetic agent that produces pain when used for induction. In this study, small doses of ketamine are being used in comparison with lignocaine and placebo for alleviating pain on propofol injection. Aims and Objectives: The aim is to assess the effect of ketamine to prevent the pain on injection of propofol and to establish an optimal dose for this purpose. Materials and Methods: We conducted a prospective randomized double-blinded study (placebo controlled) in 160 patients belonging to the American Society of Anaesthesiologists grade 1 and 2 who were posted for elective surgeries to be done under general anesthesia. They were allocated randomly into five groups. Patients were administered normal saline (NS) (Group NS), lignocaine 1.5 mg/kg (Group lignocaine), ketamine 0.1 mg/kg (Group KT1), ketamine 0.3 mg/kg (Group KT2), and ketamine 0.5 mg/kg (Group KT3) just before injection of 1% propofol in a dose of 2.5 mg/kg. Pain scores of patients were assessed at intervals of 10 s by an anesthesiologist who was blinded to the test drug. Efficacy of the pretreatment drug was assessed based on pain score and the occurrence of pain. Results: The occurrence and intensity of pain were significantly higher in the placebo group (Group NS) compared to other study groups. The occurrence of pain and pain scores were lower in the KT2 and KT3 groups compared with the KT1 and lignocaine groups. Conclusion: This study concluded that ketamine administration in a dose of 0.3 mg/kg before propofol injection is beneficial and safe in preventing pain caused by injection of propofol.

Background: Propofol is widely used for the induction of anesthesia. Sevoflurane, a popular inhalational induction agent for pediatric patients, may also be used in adults with needle phobias. Aims and Objectives: This study was done to compare the two popular induction agents, namely, propofol and sevoflurane. The speed of achieving the conditions ideal for intubation, in the background of the synergistic action of sevoflurane with vecuronium, the non-depolarizing muscle relaxant was also studied. Materials and Methods: In this prospective randomized controlled study, female patients between 20 and 65 years of age belonging to the American Society of Anaesthesiologists Grade I and II who underwent elective surgeries for breast cancer under general anesthesia were allocated randomly into two groups. Group 1 patients received propofol as the induction agent and in Group 2 sevoflurane was used as the induction agent. Induction with vital capacity breath technique using 8% sevoflurane was compared with standard induction with propofol. Results: It was found that propofol caused a greater drop in blood pressure (BP), although the time for induction was marginally lower (insignificant) with propofol. Sevoflurane potentiated the effect of vecuronium. One case in the sevoflurane group developed laryngospasm and hence was excluded from the study. Three patients in the propofol group had pain on injection. One patient from each group had abnormal transient groaning sound on induction and two patients from sevoflurane group had coughing on induction. Conclusion: Propofol and sevoflurane are equally fast in inducing anesthesia. Sevoflurane potentiates the action of non-depolarizing muscle relaxants when compared to propofol during induction and may be considered as a better option for patients in whom fall in BP is unlikely to be tolerated even for a short period.

Background: Propofol is the induction agent of choice for carrying out day care surgeries. Hypotension is one of its common adverse effects. Several drugs were evaluated in preventing this hypotension which gave inconclusive results. Aims and objectives: This study aimed to compare the efficacy of ephedrine and ketamine in preventing the hypotension due to induction with propofol. Its objective was to evaluate if KA has better efficacy than ED in reducing the incidence of hypotension following propofol induction. Materials and Methods: We had done this randomized double-blind placebo controlled study prospectively in a total of 120 patients over 18 months. Patients planning to undergo elective surgeries under general anesthesia belonging to American Society of Anaesthesiologists (ASA) Grades 1 and 2 were incorporated in the study. They were divided into three groups after randomization. They were given normal saline (Group NS), ephedrine (Group ED), and ketamine (Group KA) just before administration of propofol for induction. Parameters such as non-invasive blood pressure (BP), heart rate (HR), and oxygen saturation were noted at baseline, 1 min after propofol administration, just before endotracheal intubation and at 1, 2, and 3 min after endotracheal intubation. The efficacies of drugs were assessed based on variation in BP and HR. Results: In this study, the systolic, diastolic, and mean arterial pressure values in group KA and group ED after propofol injection and before endotracheal intubation were considerably higher than that of group NS (P 0.05). Conclusion: Ephedrine and ketamine have similar efficacy in reducing the incidence of hypotension following induction with propofol.

Dear Reader, While India has acquired global recognition as a reliable source of high quality, impurity free active pharmaceutical ingredients (APIs) and generic pharmaceuticals, Indian pharmaceutical R&D has to go a long way to enter the global pharmaceutical R&D map. The 2016 OECD report “Measuring Science Technology and Innovation” (https://www.oecd.org/sti/STI-Stats-Brochure.pdf) has a large compilation of data on R&D. India hardly finds a place in this study, except on the use of the internet & IT.As confirmed by the OECD data in 1960, 70% or more of all R&D spend globally was from Government funds. India claims to have the largest chain of R&D laboratories in the world under the CSIR/DSIR umbrella. Between 1960 to 2017, the contribution of CSIR laboratories,including once-reputed laboratories such as CDRI, Lucknow and IIIM, Jammu, to pharmaceutical research has only gone down.

Imaging flow cytometry is an emerging technology that combines the statistical power of flow cytometry with spatial and quantitative morphology of digital microscopy. It allows high-throughput imaging of cells with good spatial resolution, while they are in flow. This paper proposes a general framework for the processing/classification of cells imaged using imaging flow cytometer. Each cell is localized by finding an accurate cell contour. Then, features reflecting cell size, circularity and complexity are extracted for the classification using SVM. Unlike the conventional iterative, semi-automatic segmentation algorithms such as active contour, we propose a noniterative, fully automatic graph-based cell localization. In order to evaluate the performance of the proposed framework, we have successfully classified unstained label-free leukaemia cell-lines MOLT, K562 and HL60 from video streams captured using custom fabricated cost-effective microfluidics-based imaging flow cytometer. The proposed system is a significant development in the direction of building a cost-effective cell analysis platform that would facilitate affordable mass screening camps looking cellular morphology for disease diagnosis. Lay description In this article, we propose a novel framework for processing the raw data generated using microfluidics based imaging flow cytometers. Microfluidics microscopy or microfluidics based imaging flow cytometry (mIFC) is a recent microscopy paradigm, that combines the statistical power of flow cytometry with spatial and quantitative morphology of digital microscopy, which allows us imaging cells while they are in flow. In comparison to the conventional slide-based imaging systems, mIFC is a nascent technology enabling high throughput imaging of cells and is yet to take the form of a clinical diagnostic tool. The proposed framework process the raw data generated by the mIFC systems. The framework incorporates several steps: beginning from pre-processing of the raw video frames to enhance the contents of the cell, localising the cell by a novel, fully automatic, non-iterative graph based algorithm, extraction of different quantitative morphological parameters and subsequent classification of cells. In order to evaluate the performance of the proposed framework, we have successfully classified unstained label-free leukaemia cell-lines MOLT, K562 and HL60 from video streams captured using cost-effective microfluidics based imaging flow cytometer. The cell lines of HL60, K562 and MOLT were obtained from ATCC (American Type Culture Collection) and are separately cultured in the lab. Thus, each culture contains cells from its own category alone and thereby provides the ground truth. Each cell is localised by finding a closed cell contour by defining a directed, weighted graph from the Canny edge images of the cell such that the closed contour lies along the shortest weighted path surrounding the centroid of the cell from a starting point on a good curve segment to an immediate endpoint. Once the cell is localised, morphological features reflecting size, shape and complexity of the cells are extracted and used to develop a support vector machine based classification system. We could classify the cell-lines with good accuracy and the results were quite consistent across different cross validation experiments. We hope that imaging flow cytometers equipped with the proposed framework for image processing would enable cost-effective, automated and reliable disease screening in over-loaded facilities, which cannot afford to hire skilled personnel in large numbers. Such platforms would potentially facilitate screening camps in low income group countries; thereby transforming the current health care paradigms by enabling rapid, automated diagnosis for diseases like cancer.

This paper investigates the Jahn–Teller effect in the icosahedral cation B₈₀⁺ and compares the descent in symmetry with that in C₆₀⁺. For both cations the icosahedral ground state is a ²Hu state, which exhibits a H ⊗ (g ⊕ 2h) Jahn–Teller instability. A detailed construction of the potential energy surface of B₈₀⁺ using different DFT methods including B3LYP/6-31G(d), VWN/6-31G(d), PBE/TZP and PBE/6-31G(d) shows that, contrary to C₆₀⁺, which prefers D5d symmetry, the ground state of B₈₀⁺ adopts S₆ point group symmetry. A D3d structure is identified as a saddle point among the S₆ minima of B₈₀⁺. The distortion of D3d to S₆ in B₈₀⁺ is attributed to a superposition of Jahn–Teller and pseudo-Jahn–Teller effects. Imaginary modes, transforming as the gg representation, which are present in neutral icosahedral B₈₀, form the dominant symmetry breaking active modes. The pronounced difference between the JT effects in the boron and carbon buckyball cations is due to the plasticity of the boron caps. The calculated Jahn–Teller stabilization of B₈₀⁺ is nearly 1549 cm⁻¹ (PBE/TZP), which exceeds the stabilization of 596 cm⁻¹ computed for C₆₀⁺ at the same level.