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Remi Shrivastava,1 Megha Vijay,2 Nathalie Maneby,1 Ravishekhar Shrivastava1 1VITROBIO Research Institute, Issoire, 63500, France; 2Mudra Clincare, Navi Mumbai, IndiaCorrespondence: Ravishekhar Shrivastava Email rs@vitrobio.comBackground: Covid-19 infection is a multifactorial disease where the virus mainly enters through the nasal cavity, grows, triggers inflammation, and destroys nasal mucosa cells, allowing systemic virus entry and infection of other organs. When symptoms appear, the disease physiopathology is already established. The immune system tries to control the infection but if the infection persists, it gets tired, fatigued, stressed, and finally, there is burnout. Therefore, an effective treatment should be multi-targeted and should not focus only on one parameter. Minimizing virus concentration, reducing nasal mucosa inflammation, and keeping the nasal surface clean should lessen systemic infection and the probability of developing severe respiratory distress. We evaluated clinical efficacy and safety of an osmotic nasal surface cleaning, virus and cytokine trapping polymeric film, in early-stage Covid-19 positive symptomatic patients.Methods: A randomized, multicentric, observational study was performed to evaluate the efficacy and safety of the osmotic film in 213 patients, randomized in 2 equal arms, and confined for 14-days just after the RT-PCR+ test. Due to ethical reasons, all patients received symptomatic treatments (ST). In addition, the patients in Arm-1 received the test product (ST+TP, 2– 3 sprays, 4– 5 times/day) for 14-days. Leicester Cough Questionnaire, Visual Analogue Scale, and Covid-19-associated symptoms such as fever, pain, taste, smell, and headache were evaluated daily. Home-confined patients were immediately hospitalized in case of aggravation of any life-threatening clinical sign.Results: Among 213 patients, 98 in the ST and 102 in the ST+TP group completed the study. Thirteen patients did not complete the study as 8 in the ST group and 5 in the ST+TP group were hospitalized during the study due to low blood oxygen levels or sudden health deterioration and were excluded from the study. In the remaining control standard treatment group (n=98), clinical signs sharply aggravated on day 1– 2 followed by stabilisation between days 3– 6 and progressive reduction thereafter. In the test product group (n=102), symptoms were stabilized just after the first application and improved progressively. Only 42/102 patients in the test product group presented nasal discharge or irritation due to the osmotic properties of the product.Conclusion: The continuous multi-target approach of detaching and neutralizing virus particles and pro-inflammatory cytokines from the nasal surface to minimize systemic virus exposure is a very logical and efficient approach to avoid Covid-19-induced systemic pathology.Keywords: clinical trial, Covid-19, osmotic filmogen barrier

Ravi Shrivastava,1 Remi Shrivastava,1 Bianca Johansen,1 Thibault Allain2,3 1VITROBIO Research Institute, Issoire, 63500, France; 2Laboratoire SANABEL, Paris, 75011, France; 3UMR 152 Pharma Dev, Université de Toulouse, IRD, UPS, Toulouse, FranceCorrespondence: Ravi Shrivastava Email rs@vitrobio.comBackground: Covid-19 infection starts in the nasal cavity when viral S1 and RBD proteins bind to the host cell ACE2 receptors, the virus multiplies, causes cell lysis, and enters the circulation. This triggers a strong cytokine release and inflammation of the nasal mucosa. A multitarget approach of cleaning the nasal mucosa and suppressing chances of nasal and systemic inflammation should minimize severe respiratory consequences. Unfortunately, no such treatments are yet available.Methods: We describe the conception of an osmotic polymeric film using an in vitro nasal mucosa mimicking model, containing polymers to neutralize Covid-19 specific viral S1, RBD proteins and selected proinflammatory cytokines.Results: The filmogen barrier forms a stable and osmotic film on the nasal mucosa. Hypotonic liquid exudation from the nasal surface detaches and drains the inflammatory cytokines and other contaminants towards the film where selected polymers bind and neutralize SARS-CoV-2 spike S1 and RBD protein as well as Covid-19 disease-specific key pro-inflammatory IL-6, TNF-α, IL-10, IL-13, and GM-CSF cytokines.Conclusion: Minimizing the nasal surface concentration of pro-inflammatory cytokines and viruses should help nasal mucosa repair and avoid immune stress. This nearly instant, simple, scientific, safe, and logical approach should help attenuate Covid-19 induced systemic inflammation at an early stage without being affected by viral S1 spike protein mutations.Keywords: filmogen glycerol, antiviral, anti-cytokines, anti-inflammatory, Covid-19, S1, RBD

Cefepime/zidebactam is in clinical development for the treatment of carbapenem-resistant Gram-negative infections. MICs of cefepime/zidebactam (1:1) and comparators against Enterobacterales (n = 563), Pseudomonas (n = 172) and Acinetobacter baumannii (n =181) collected from 15 Greek hospitals (2014-2018) were determined by reference broth microdilution method. The isolates exhibited high carbapenem resistance rates [(Enterobacterales (75%), Pseudomonas (75%) and A. baumannii (98.3%)]. Cefepime/zidebactam showed MIC50/90 of 0.5/2 mg/L, against Enterobacterales including metallo-β-lactamases (MBL)-producers. Reduced susceptibility rates to tigecycline (16.8%), colistin (47.4%), ceftazidime/avibactam (59.8%), and imipenem/relebactam (61%) indicated high prevalence of multi-drug resistance among Greek Enterobacterales. Cefepime/zidebactam exhibited MIC50/90 of 8/16 mg/L against Pseudomonas including MBL-producers. The MIC50/90 of ceftazidime/avibactam and imipenem/relebactam were high (≥32 mg/L). Cefepime/zidebactam showed MIC90 of 64 mg/L against A. baumannii which is within its therapeutic scope. Other antibiotics including colistin showed limited activity against A. baumannii. The activity of cefepime/zidebactam against multi-drug-resistant isolates is attributable to zidebactam mediated novel β-lactam-enhancer mechanism. © 2021 Elsevier Inc.

Background: Angiogenesis is a necessary step in the growth of any tumour and metastasis. Vascular endothelial growth factor (VEGF) is a major mediator of breast cancer angiogenesis. The expression of VEGF by breast tumours has been previously correlated with a poor prognosis in the pathogenesis of breast cancer. Method: In this cross-sectional descriptive study 54 women were enrolled over the period of 2 years. This study was aimed to determine the correlation between serum and tissue levels of VEGF-A and prognosis in carcinoma of breast cases. It also tried to correlate the aggressiveness of the disease with serum and tissue levels of VEGF-A in the subject population. Results: In benign cases, preoperative serum VEGF-A (sVEGF-A) levels remained within 3000 pg/ml while post-operative sVEGF-A levels never went beyond 2300pg/ml. In the majority of carcinoma breast cases, preoperative sVEGF-A levels remain within 4000 pg/ml while post-operative sVEGF-A levels never went beyond 3000pg/ml. All the benign lesions were negative for tissue VEGF-A (tVEGF-A). While all malignant lesions were positive for tVEGF-A in the immunohistochemistry (IHC) study. Patients with a malignant lesion of higher tumour grades were having high tVEGF-A readings (2+ or more). In this study higher nodal status was associated with higher tVEGF-A reading. Similarly, tVEGF-A was higher in ER/PR/Her2neu negative cases. Conclusions: Determination of VEGF-A can be considered a promising, but investigative and prognostic tool. Large prospective studies are necessary to better define the relationship of prognosis to angiogenesis and VEGF-A.

Department of Chemistry IPS Academy, Indore-452 012, Madhya Pradesh, India E-mail : drpremlataguptachem@gmail.com Manuscript received 20 December 2017, revised 31 January 2018, accepted 19 February 2018 A series of N'-aryllidene-2-aryl-1H-benzo[d]imidazole-4-carbohydrazide (Schiff bases) 3a1-3d4 were synthesized by condensation reaction of 2-aryl-1H-benzo[d]imidazole-4-carbohydrazide (2a-2d) with substituted aromatic aldehyde. The characterization of all these novel synthesized compounds 3a1-3d4 were established on the basis of spectral studies (IR, NMR and Mass) and elemental analysis. The anti-microbial activities of these compounds were tested in vitro by agar diffusion cup-plate method against two Gram-negative Escherichia coli, Pseudomonas aeruginosa and two Gram-positive Staphylococcus aureus, Bacillus substilis bacteria and fungi Candida albicans at 100 µg/ml concentrations. All these compounds have displayed significant or moderate activities against the test microorganisms

Ravi Shrivastava, Nathalie Cucuat, Monika Rousse, Thomas Weigand, Pedro Neto, Claire Janicot, Christiane Shrivastava VITROBIO Research Institute, Issoire, France Purpose: Incidence of chronic wounds is constantly rising worldwide, but all currently available treatments are intended either to provide symptomatic relief or to assist cicatrization to some extent, but not to directly stimulate cellular growth. Physiologically, chronic wound healing simply requires cell growth to fill the injured cavity. To grow, our cells need to attach onto a cushion, called extracellular matrix (ECM), secreted by the mother cells and composed of multiple proteins. Recent scientific works prove that the concentration of certain matrix metalloproteinases (MMPs) is extremely high in all chronic wounds and, because of their proteolytic nature, some MMPs completely degrade the ECM, hindering cell attachment and cell growth. The aim of this study was to identify, neutralize, and eliminate these MMPs from the wound surface so as to design an effective treatment for chronic wounds. Methods: Acute and chronic models of human epithelial and fibroblast cells were prepared on a defined ECM cushion in vitro and MMPs were added in the culture medium to identify the MMPs causing ECM disintegration for each cell type. ECM-degrading MMPs were then incubated with selected procyanidin-rich plant extracts (PCDs) and cell growth was reanalyzed. Results: It was observed that: 1) multiple MMPs are involved in cellular matrix destruction; 2) ECM-destroying MMPs are specific with respect to cell type; and 3) specific PCDs may bind and neutralize selected MMPs. Conclusion: Topical application of specific plant PCDs to selectively neutralize ECM-destroying MMPs in acute and chronic wounds represents a novel approach for the treatment of superficial and deep skin wounds. Keywords: extra cellular matrix (ECM), matrix metalloproteinases, procyanidins (PCDs), tannins, ulcers

APPROXIMATION OF FUNCTION OF CLASS Lip(α, p) BY [F, d n ] MEAN

This paper examines the efficiency of fish marketing at Bhubaneswar city. A sample of 5 wholesalers, 5 commission agents and 40 retailers were taken for primary data collection on.prices of fish and marketing costs. The channel III shows that 85 percent of the demand for fish was met by fish producers of Andhra Pradesh. The producers' share in consumers rupee was highest for local producers and lowest for non local producers. The largest component of price spread and net margin was attributed to retailers followed by wholesalers and commission agents. The net income of non local producers-cum-wholesalers was found to be highest because they handle larger quantity of fish. Also, the return to one rupee investment was recorded to be more than 100 percent. There exists a scope of earning super normal profit by intermediaries because market was not perfectly competitive. It is recommended that government should formulate suitable aqua price policy for eliminating imperfection from the market.

This paper examines the efficiency of fish marketing at Bhubaneswar city. A sample of 5 wholesalers, 5 commission agents and 40 retailers were taken for primary data collection on.prices of fish and marketing costs. The channel III shows that 85 percent of the demand for fish was met by fish producers of Andhra Pradesh. The producers' share in consumers rupee was highest for local producers and lowest for non local producers. The largest component of price spread and net margin was attributed to retailers followed by wholesalers and commission agents. The net income of non local producers-cum-wholesalers was found to be highest because they handle larger quantity of fish. Also, the return to one rupee investment was recorded to be more than 100 percent. There exists a scope of earning super normal profit by intermediaries because market was not perfectly competitive. It is recommended that government should formulate suitable aqua price policy for eliminating imperfection from the market.

The aim of the paper is to show the validity of results of Imdad [7] in a domain which is not necessarily starshaped and mappings are not necessarily linear. Our results also improve, extend and generalize various existing known results in the literature.