An Updated Systematic Review of the Therapeutic Role of Hydroxychloroquine in Coronavirus Disease-19 (COVID-19).

BACKGROUND AND OBJECTIVE: The world is currently experiencing the Coronavirus Disease-19 (COVID-19) pandemic. There is no approved drug for the definitive treatment of the disease. Various drugs are being tried for the treatment of COVID-19, including hydroxychloroquine (HCQ). This study was performed to systematically review the therapeutic role of HCQ in COVID-19 from the available literature. METHODS: PubMed, Embase, ClinicalTrials.gov, ICTRP (WHO), Cochrane Library databases, and two pre-print servers (medRxiv.org and Research Square) were searched for clinical studies that evaluated the therapeutic role of HCQ on COVID-19 until 10 May 2020. The available studies were critically analyzed and the data were extracted. RESULTS: A total of 663 articles were screened and 12 clinical studies (seven peer-reviewed and published studies and five non-peer-reviewed studies from pre-print servers) with a total sample size of 3543 patients were included. Some of the clinical studies demonstrated good virological and clinical outcomes with HCQ alone or in combination with azithromycin in COVID-19 patients, although the studies had major methodological limitations. Some of the other studies showed negative results with HCQ therapy along with the risk of adverse reactions. CONCLUSION: The results of efficacy and safety of HCQ in COVID-19, as obtained from the clinical studies, are not satisfactory, although many of these studies had major methodological limitations. Stronger evidence from well-designed robust randomized clinical trials is required before conclusively determining the role of HCQ in the treatment of COVID-19. Clinical prudence is required in advocating HCQ as a therapeutic armamentarium in COVID-19.

Synthesis, characterization and unravelling the molecular interaction of new bioactive 4-hydroxycoumarin derivative with biopolymer: Insights from spectroscopic and theoretical aspect.

In the progress of small molecule as drug candidates, 4-hydroxycoumarin based compounds bearing a crucial place as potent antibiotic agents with appreciable safety in drug invention. Being synthetically and easily obtainable, 4-hydroxycoumarin related compounds with planar structure have been promoted predominantly as DNA targeting agent. Nevertheless, here we elucidate the synthesis, characterization and theoretical study of bio-active small molecule 4-hydroxy-3,4'-bichromenyl-2,2'-dione (4HBD). Then we have illuminated the binding interactions of 4HBD with calf thymus DNA (ctDNA), which is particularly designed for biological application. Extensive investigations of the binding of 4HBD with ctDNA are provided by utilizing multi-spectroscopic and molecular docking approaches, including UV-vis absorbance, steady-state, time-resolved fluorescence spectroscopy and circular dichroism study. The calculated binding and quenching constant value from quantitative data analysis of absorption and emission spectroscopy shows that 4HBD binds to the ctDNA groove. Further confirmation of the same is found by comparative displacement and iodide quenching studies. Negative enthalpy, negative free energy and positive entropy change imply a hydrophobic force monitors the association of 4HBD with the biomacromolecule. Interestingly the small molecule (4HBD) shows potential anti-bacterial activity against the model pathogenic gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Bacillus subtilis and Staphylococcus aureus) bacteria. The noncytotoxic nature of the 4HBD is demonstrated in vitro with the help of MTT assay by normal kidney epithelial (NKE), breast cancer cells (MCF-7) and human prostate cancer cell (PC3) lines. Hemolytic assay exhibits insignificant hemolysis of human erythrocyte cells at the minimum inhibitory concentration (MIC) of these tested bacteria. In this regard the present invention of 4-hydroxycoumarin based antimicrobial and noncytotoxic 4HBD molecule holds future promise in the development of new antibiotics.

Amphiphilic Peptide-Based Supramolecular, Noncytotoxic, Stimuli-Responsive Hydrogels with Antibacterial Activity.

A series of peptides with a long fatty acyl chain covalently attached to the C-terminal part and a free amine (-NH2) group at the N-terminus have been designed so that these molecules can be assembled in aqueous medium by using various noncovalent interactions. Five different peptide amphiphiles with a general chemical formula [H2N-(CH2)nCONH-Phe-CONHC12 (n = 1-5, C12 = dodecylamine)] have been synthesized, characterized, and examined for self-assembly and hydrogelation. All of these molecules [P1 (n = 1), P2 (n = 2), P3 (n = 3), P4 (n = 4), P5 (n = 5)] form thermoresponsive hydrogels in water (pH 6.6) with a nanofibrillar network structure. Interestingly, the hydrogels obtained from compounds P4 and P5 exhibit potential antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis) and Gram-negative bacteria (Escherichia coli). Dose-dependent cell-viability studies using MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) by taking human lung carcinoma (A549) cells vividly demonstrates the noncytotoxic nature of these gelator molecules in vitro. Hemolytic studies show nonsignificant or little hemolysis of human erythrocyte cells at the minimum inhibitory concentration (MIC) of these tested bacteria. Interestingly, it has been found that these antibacterial noncytotoxic hydrogels exhibit proteolytic resistance toward the enzymes proteinase K and chymotrypsin. Moreover, the gel strength and gel recovery time have been successfully modulated by varying the alkyl chain length of the N-terminally located amino acid residues. Similarly, the thermal stability of these hydrogels has been nicely tuned by altering the alkyl chain length of the N-terminally located amino acid residues. In the era of antibiotic-resistant strains of bacteria, the discovery of this new class of peptide-based antibacterial, proteolytically stable, injectable, and noncytotoxic soft materials holds future promise for the development of new antibiotics.

Fatal Nevirapine-Induced Toxic Epidermal Necrolysis in a HIV Infected Patient.

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are the most Severe Cutaneous Adverse Reactions (SCARs) which mainly caused by exposure to drugs and having significant morbidity and mortality. TEN represents an immunologic reaction to a foreign antigen and is most often caused by drugs. Nevirapine (NVP), a non-nucleoside reverse transcriptase inhibitor (NNRTI) is an important component of Highly Active Antiretroviral Therapy (HAART). It is sometimes associated with life-threatening adverse reactions. Here, we report the fatal case of 72-year-old male who developed TEN secondary to intake of nevirapine. This fatal case report will increase awareness among treating physicians for careful monitoring of patients on NNRTI-based antiretroviral therapy and better counseling of the patient on NVP regimen for early identification and reporting of SCARs so that fatalities due to adverse drug reactions can be prevented with timely intervention.

Pedal edema associated with atypical antipsychotics.

This study describes a patient diagnosed as a case of bipolar affective disorder complaining of bothersome incidence of pedal edema 1 month after the initiation of atypical antipsychotic regimen with risperidone and quetiapine. All hematological and biochemical profiles were found to be normal. On discontinuation of risperidone, the condition remained unresolved even after 2 weeks, and the edema progressed reaching her calves. On tapering the dose of quetiapine, she started showing gradual improvement in edematous condition. Quetiapine was slowly discontinued. No further recurrence of edema occurred, and hence, no further medication changes were implemented. Pedal edema was found to be resolved within weeks of dechallenge of the regimen. Naranjo adverse drug reaction probability scale gave a score of 7 which denotes "probable" adverse drug reaction with quetiapine.

Efficacy and tolerability of topical sertaconazole versus topical terbinafine in localized dermatophytosis: A randomized, observer-blind, parallel group study.

OBJECTIVE: Epidermal dermatophyte infections most commonly manifest as tinea corporis or tinea cruris. Topical azole antifungals are commonly used in their treatment but literature suggests that most require twice-daily application and provide lower cure rates than the allylamine antifungal terbinafine. We conducted a head-to-head comparison of the effectiveness of the once-daily topical azole, sertaconazole, with terbinafine in these infections. MATERIALS AND METHODS: We conducted a randomized, observer-blind, parallel group study (Clinical Trial Registry India [CTRI]/2014/09/005029) with adult patients of either sex presenting with localized lesions. The clinical diagnosis was confirmed by potassium hydroxide smear microscopy of skin scrapings. After baseline assessment of erythema, scaling, and pruritus, patients applied either of the two study drugs once daily for 2 weeks. If clinical cure was not seen at 2 weeks, but improvement was noted, application was continued for further 2 weeks. Patients deemed to be clinical failure at 2 weeks were switched to oral antifungals. RESULTS: Overall 88 patients on sertaconazole and 91 on terbinafine were analyzed. At 2 weeks, the clinical cure rates were comparable at 77.27% (95% confidence interval [CI]: 68.52%-86.03%) for sertaconazole and 73.63% (95% CI 64.57%-82.68%) for terbinafine (P = 0.606). Fourteen patients in either group improved and on further treatment showed complete healing by another 2 weeks. The final cure rate at 4 weeks was also comparable at 93.18% (95% CI 88.75%-97.62%) and 89.01% (95% CI 82.59%-95.44%), respectively (P = 0.914). At 2 weeks, 6 (6.82%) sertaconazole and 10 (10.99%) terbinafine recipients were considered as "clinical failure." Tolerability of both preparations was excellent. CONCLUSION: Despite the limitations of an observer-blind study without microbiological support, the results suggest that once-daily topical sertaconazole is as effective as terbinafine in localized tinea infections.

C-deletion in exon 4 codon 63 of p53 gene as a molecular marker for oral squamous cell carcinoma: A preliminary study.

BACKGROUND: Exfoliated oral cancer cells in saliva samples from patients with oral squamous cell carcinoma (OSCC) can be used to determine the incidence and type of mutations of the p53 tumor suppressor gene. The purpose of this study was to identify C-deletion mutation in exon 4 codon 63 of p53 gene in the saliva of OSCC patients by polymerase chain reaction (PCR). MATERIALS AND METHODS: Saliva samples of 20 newly histopathologically diagnosed OSCC patients and 5 healthy volunteers were subjected to isolation of the total genomic DNA and PCR amplification for C-deletion on exon 4 of p53 gene. The resulting products were resolved by agarose gel electrophoresis, viewed and photographed on ultraviolet-transilluminator. RESULTS: The relationship between the frequencies of genetic alterations was assessed by Chi-square test. Differences with values of P < 0.05 were statistically significant. CONCLUSION: The study concluded a 100% presence of C-deletion mutation in exon 4 codon 63 of p53 in the saliva of OSCC patients. This study suggests that detection of mutation in exon 4 codon 63 of p53 by PCR is a fast, reliable, accurate, and sensitive molecular method for OSCC diagnosis.

Shoot cultures of Hoppea fastigiata (Griseb.) C.B. Clarke as potential source of neuroprotective xanthones.

Hoppea fastigiata, an annual medicinal herb belonging to the Gentianaceae, is mostly found in South Asian countries, and is used by local tribes for various brain-related ailments. The genus possesses a unique class of compounds, xanthones, which are known for their potential against Alzheimer's and Parkinson's diseases. Limited availability and the potential pharmacological significance of the plants has led to the establishment of in vitro cultures of H. fastigiata and study of its neuroprotective principles. In vitro plantlets were established from the apical meristem of the plant in Murashige and Skoog medium with a combination of the phytohormones 6-benzylaminopurine (1 mg/L) and kinetin (0.1 mg/L), which was found to be efficacious with a growth index of 0.9 ± 0.01 after 30 days. Four different solvent extracts of in vitro cultures were evaluated for acetylcholinesterase (AChE) and monoamine oxidase A and B (MAO-A and MAO-B) inhibitory activities, amongst which the ethanolic extract showed the lowest IC50 value in all the assays. Three major compounds were isolated from the ethanolic extract and structurally confirmed as 1,5,7-trihydroxy-3-methoxyxanthone (1), 1,5-dihydroxy-3,7-dimethoxyxanthone (2) and 1,3,5-trihydroxy-8-methoxyxanthone (3). Compound 3 showed the strongest AChE inhibitory activity with mixed-type inhibition. Compounds 1 and 2 also showed promising AChE inhibitory properties with mixed and non-competitive types of inhibition, respectively. Compounds 1 and 2 showed inhibition of MAO-A (mixed and competitive, respectively) and compounds 2 and 3 showed inhibition of MAO-B (competitive and mixed, respectively). Extracts and isolated compounds showed good antioxidant capacities. The ethanolic extract and compound 2 showed the strongest antioxidant activities among the other solvent extracts and compounds, respectively.

Oxcarbazepine induced maculopapular rash - a case report.

Unlike carbamazepine, newer anti epileptic drug like oxcarbazepine, reports fewer side effects. In this report we describe a case of oxcarbazepine induced maculopapular rash probably happened because of a drug interaction with isoniazid, and a brief review of the existing literature is presented herewith. A 40-year-old male patient received oxcarbazepine 300mg twice daily along with other anti-tubercular drugs including isoniazid (300mg) once daily since two days. Extensive cutaneous rash with intense itching developed which subsided on discontinuation of oxcarbazepine. This case highlights the fact that there is a potential possibility of drug-drug interaction between oxcarbazepine and isoniazid and concomitant use of these two drugs should better be avoided during clinical practice.

A questionnaire-based survey to ascertain the views of clinicians regarding rational use of antibiotics in teaching hospitals of Kolkata.

OBJECTIVES: The objective was to assess the views of clinicians in teaching hospitals of Kolkata regarding the use of antibiotics in their own hospitals, focusing on perceived misuse, reasons behind such misuse and feasible remedial measures. MATERIALS AND METHODS: A total of 200 clinicians from core clinical disciplines was approached in six teaching hospitals of Kolkata through purposive sampling. A structured, validated questionnaire adopted from published studies and modified to suit the responding population was completed by consenting respondents through face-to-face interaction with a single interviewer. Respondents were free to leave out questions they did not wish to answer. RESULTS: Among 130 participating clinicians (65% of approached), all felt that antibiotic misuse occurs in various hospital settings; 72 (55.4% of the respondents) felt it was a frequent occurrence and needed major rectification. Cough and cold (78.5%), fever (65.4%), and diarrhea (62.3%) were perceived to be the commonest conditions of antibiotic misuse. About half (50.76%) felt that oral preparations were more misused compared to injectable or topical ones. Among oral antibiotics, co-amoxiclav (66.9%) and cefpodoxime (63.07%) whereas among parenteral ones, ceftriaxone and other third generation cephalosporins (74.6%) followed by piperacillin-tazobactam (61.5%) were selected as the most misused ones. Deficient training in rational use of medicines (70.7%) and absence of institutional antibiotic policy (67.7%) were listed as the two most important predisposing factors. Training of medical students and interns in rational antibiotic use (78.5%), implementation of antibiotic policy (76.9%), improvement in microbiology support (70.7%), and regular surveillance on this issue (64.6%) were cited as the principal remedial measures. CONCLUSIONS: Clinicians acknowledge that the misuse of antibiotics is an important problem in their hospitals. A system of clinical audit of antibiotic usage, improved microbiology support and implementation of antibiotic policy can help to promote rational use of antimicrobial agents.

A Suspected Case of Efavirenz-Induced Stevens-Johnson Syndrome.

A 23-year-old human immunodeficiency virus (HIV)-infected Indian woman was admitted to a tertiary care hospital with generalized erythematosus rash all over her body with difficulty in swallowing for the previous 3 days. She also presented with swelling of the lips and redness of both eyes along with nausea, anorexia, slight headache, and fever, which appeared immediately after the initiation of a new regime of antiretroviral treatment with tenofovir (300 mg once daily), lamivudine (300 mg once daily), and efavirenz (600 mg once daily). Presumptive diagnosis of efavirenz-induced Stevens-Johnson syndrome was made after excluding other causes. Efavirenz was withdrawn, followed by tenofovir and lamivudine. Supportive care was provided to the patient during her hospital stay. She recovered after 2 weeks. Thus, strict vigilance of adverse drug reaction is required in patients on a highly active antiretroviral therapy regimen.

Exploration of novel rhizospheric yeast isolate as fertilizing soil inoculant for improvement of maize cultivation.

BACKGROUND: Chemical input in agriculture is a common practice but makes a serious impact to the environment. In this context, soil isolates having multiple plant growth-promoting (PGP) attributes have been studied. The isolates were tested for their PO4 and Zn solubilization, indole-3-acetic acid (IAA) production and N2 fixation ability. The selected isolate SSm-39 was characterized to molecular level. The isolate SSm-39 was applied to maize cultivation in various combinations with chemical fertilizers. Also, the chemical and microbial status of soil, its effect on maize growth and yield were investigated. RESULTS: Isolate SSm-39 found most suitable for its PGP attributes and identified as Candida tropicalis. The inoculant (100%) with reduced dose of chemical fertilizer (T5) application notably increased the growth and yield performance of maize. It has improved grain quality by 85% as indicated by carbohydrate and protein content, in comparison to uninoculated control (T3). Soil nutrient status was found to increase twofold with T5 treatment compared with T3 treatment. Enhanced soil nutrient quality supported microbial growth and diversity, thus accelerating soil enzymatic activities. CONCLUSION: The results validate the multiple PGP traits of C. tropicalis SSm-39, advocating reduction of chemical fertilizer for maize cultivation.

Impact on behavioral changes due to chronic use of sertraline in Wistar albino rats.

AIM: Despite having better tolerability and a wide range of clinical applications over other antidepressants, selective serotonin reuptake inhibitors (SSRIs) are also known to be associated with serious adverse effects like suicidal ideation on chronic use. The present study had explored the impact of the chronic use of sertraline, an SSRI, on the behavioral changes in Wistar albino rats. MATERIALS AND METHODS: The study was conducted on 30 Wistar albino rats of either sex; divided into five groups. Four groups were subjected to chronic mild stress induced by using various stressors randomly scheduled in a week and continued for a period of 3 weeks. The stressed rodents were subjected to sertraline treatment for 9 weeks in different human therapeutic doses extrapolated to animal doses. Behavioral changes were monitored, assessed, and evaluated throughout the treatment phase with the help of tests such as locomotor activity test, forced swim test, tail suspension test, antianxiety test, and sucrose preference test (SPT). RESULTS: All tests except SPT, demonstrated significant (P < 0.05) reduction in depressive-like activity in the stressed rodents by the mid-treatment phase, followed by an abrupt onset of the depressive state by the end of the treatment phase. SPT showed a significant (P < 0.05) increase in sucrose consumption throughout the treatment phase. CONCLUSION: Behavioral changes following chronic sertraline administration conferred gradual remission of depression state on initial treatment phase, followed by a reversal of effect on chronic use.

Metronidazole-Induced Bullous Pemphigoid: A Case Report.

Bullous pemphigoid is an autoimmune cutaneous blistering disorder, the exact pathogenesis of which is still not fully elucidated. Drug-induced bullous pemphigoid eruptions are rare but have been reported earlier with the use of frusemide, psoralens, ibuprofen, galantamine hydrobromide, ACE inhibitors like captopril, spironolactone, penicillin, ampicillin, levofloxacin, penicillamine. We hereby report a case of metronidazole induced bullous pemphigoid (BP) in a 52-year-old male patient suffering from liver abscess following 4 days of drug administration. The skin biopsy findings obtained from the patient were consistent with the diagnosis of bullous pemphigoid (BP). Metronidazole was discontinued and symptomatic treatment was offered to the patient. Following withdrawal of metronidazole, the bullae subsided in the next 7-10 days without any significant residual scarring. The causality assessment performed as per the Naranjo algorithm revealed the case to be probable (Naranjo score 7).

A Case of Self-treatment Induced Recurrent Fixed Drug Eruptions Associated with the Use of Different Fixed Dose Combinations of Fluoroquinolone-Nitroimidazole.

A young male patient used fixed dose combinations of different fluoroquinolones and nitroimidazoles several times in the last few years for self-treating repeated episodes of diarrhea and loose motion. Each time, he experienced fixed drug eruptions that increased in number and severity on subsequent occasions. Suspecting association between the drug and the rashes, the patient each time discontinued the treatment prematurely, and preferred to switch to a similar formulation next time, but with different molecules of fluoroquinolone (ciprofloxacin or ofloxacin) and nitroimidazole (tinidazole or ornidazole). He could not however avoid the rash. This time the patient presented with multiple, round-to-oval, well-defined, hyperpigmented cutaneous patches of different dimensions, all over the body. He appeared to have run out of options and therefore consulted us seeking advice on how he should treat himself next time he suffered from diarrhea. Causality assessment by Naranjo's algorithm revealed a definite relationship between the cutaneous adverse reaction and the offending drug. He was counselled regarding medication in general and advised, in particular, to avoid the tendency to self-treat any future episode of diarrhea.

Azithromycin-induced rash in a patient of infectious mononucleosis - a case report with review of literature.

Antibiotic induced skin rash in setting of infectious mononucleosis is often encountered in clinical practice. However, macrolides like azithromycin are considered relatively safe and till date only two cases of azithromycin induced rash in setting of infectious mononucleosis have been reported. The following report illustrates the case of a 23-year-old man suffering from infectious mononucleosis who exhibited a generalized cutaneous rash following treatment with azithromycin. Using the Naranjo ADR probability scale, this case of acute onset rash following azithromycin administration was found to be in 'probable' category. The mechanism of antibiotic-induced rash in patients suffering from infectious mononucleosis is incompletely understood. It has been suggested that the rash could result from virus mediated immunomodulation or due to altered drug metabolism. The report calls for cautious use of antibiotics in the setting of suspected viral infections like infectious mononucleosis as injudicious use might increase the risk of deleterious skin reactions and increase the cost of healthcare.

Diclofenac-serratiopeptidase combination induced stevens - johnson syndrome - a rare case report with review of literature.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions (SCAR) which are frequently caused by exposure to drugs and cause significant morbidity and mortality. A careful literature search revealed that only a few reports of diclofenac induced and one case of serratiopeptidase associated case report of SJS or TEN have been published till date. However, to our knowledge, no case report of diclofenac-serratiopeptidase combination induced SJS have been published till date. In this backdrop, we describe the first case of a 62-year-old woman who developed diffuse, erythematous rash on face, trunk and both extremities which later turned into blisters following five day treatment with diclofenac and serratiopeptidase combination. There was extensive ulceration of buccal, genital and ocular mucosa. The body surface area involvement of the patient at the time of presentation was 9%. A provisional diagnosis of SJS was made by the treating physician. After administration of intravenous antibiotic, topical antiseptic, anti-histamine, topical lubricants, fluid therapy and parenteral nutrition patient recovered and were discharged.