Antimicrobial lipids loaded on lectin display reduced MIC, curtail pathogenesis and protect zebrafish from reinfection by immunomodulation.

Antibiotic resistance and re-emergence of highly resistant pathogens is a grave concern everywhere and this has consequences for all kinds of human activities. Herein, we showed that N-palmitoylethanolamine-derived cationic lipid (cN16E) had a lower minimum inhibitory concentration (MIC) against both Gram-positive and Gram-negative bacteria when it was loaded with Butea monosperma seed lectin (BMSL). The analysis using lectin-FITC conjugate labelling indicated that the improved antibacterial activity of BMSL conjugation was due to bacterial cell surface glycan recognition. Live and dead staining experiments revealed that the BMSL-cN16E conjugate (BcN16E) exerts antibacterial activity by damaging the bacterial membrane. BcN16E antimicrobial activity was demonstrated using an infected zebrafish animal model because humans have 70 % genetic similarity to zebrafish. BcN16E therapeutic potential was established successfully by rescuing fish infected with uropathogenic Escherichia coli (UPEC). Remarkably, the rescued infected fish treated with BcN16E prevented reinfection without further therapy, indicating BcN16E immunomodulatory potential. Thus, the study examined the expression of immune-related genes, including tnfα, ifnγ, il-1ß, il-4, il-10, tlr-2, etc. There was a significant elevation in the expression of all these genes compared to control and fish treated with BMSL or cN16E alone. Interestingly, when the rescued zebrafish were reinfected with the same pathogen, the levels of expression of these genes were many folds higher than seen earlier. Radial immune diffusion analyses (RIA) using zebrafish serum revealed antibody production during the initial infection and treatment. Interestingly, reinfected fish had significant immunoprecipitation in RIA, a feature absent in the groups treated with cN16E, BMSL, and control. These results clearly show that the BcN16E complex not only rescued infected zebrafish but also conferred long-lasting protection in terms of immunomodulation that protects against multiple reinfections. The findings support that BcN16E has immense potential as a novel immunostimulant for various biomedical applications.

Lectins as the prominent potential to deliver bioactive metal nanoparticles by recognizing cell surface glycans.

Lectins are renowned for recognizing specific carbohydrates, but there is evidence that they can bind to other endogenous ligands. Therefore, lectin can be used as a carrier to recognize glycoconjugates on the cell surface. The anticancer, antibacterial, and immunomodulatory properties of some lectins are established. Metal nanoparticles (MNPs) have been used in various fields recently, but their documented toxicity has raised questions about their suitability for biomedical uses. The advantages of MNPs can be realized if we deliver the NPs to the site of action; as a result, NPs may achieve greater therapeutic efficiency at lower doses with less toxicity. The use of carbohydrate specificity by lectin MNPs conjugates for diagnostics and therapeutics was addressed. The review summarised the multidimensional application of lectins and described their potential for delivery of MNPs in future drug development.

Hybrid of Metapenaeus dobsoni lectin and platinum nanoparticles exert antimicrobial and immunostimulatory effects to reduce bacterial bioburden in infected Nile tilapia.

A novel antibacterial immunostimulant using Platinum nanoparticles (PtNPs) and lectin from Metapenaeus dobsoni (Md-Lec) was developed. The Md-Lec and PtNPs (Pt-lec) hybrid formed through non-covalent interaction exhibits antimicrobial activity against fish specific pathogens by affecting membrane integrity and producing excess reactive oxygen species. The therapeutic efficacy of Pt-lec was demonstrated through rescuing Aeromonas hydrophila infected Nile Tilapia. Pt-lec prevents the infection spreading and reduces the bacterial bioburden in less than 12 h, and as a result of this the fish were restored to normalcy. To assess immunostimulation, we studied the expression of three different immune related genes, namely LEC, Myd88 and COX-2 in the gills, liver, spleen and kidney of fish under various experimental conditions. Our results showed that Pt-lec treatment appeared to be better when compared to lectin alone in enhancing the expression of Myd88 and COX-2, but LEC was not as expected. These results suggest that Pt-lec has the ability to protect Nile Tilapia against bacterial infection by restricting bacterial bioburden through their direct effects on the bacterial membrane and indirectly through their effects on host immune-related gene expression. This hybrid could have potential "green" application in fish farming in rescuing infected animals when compared to widely and unregulated antibiotics.

Activity of lipid-loaded lectin against co-infection of Candida albicans and Staphylococcus aureus using the zebrafish model.

AIM: Nosocomial infection caused by mixed species of methicillin-resistant Staphylococcus aureus (MRSA) and Candida albicans (CA) is difficult to manage with existing antimicrobials, particularly in the presence of mixed-species biofilm. This study evaluates the activity of cationic lipid, specifically functionalized with lectin, against mixed biofilms of MRSA and CA and their effectiveness in vivo using the zebrafish model. METHODS AND RESULTS: The present study demonstrates for the first time the antimicrobial activity of 2-((N-[2-hydroxyethyl]palmitamido)methyl)-1-methylpyridin-1-ium iodide (cN16E) against MRSA and mixed species of MRSA + CA. The cN16E functionalized with Butea monosperma seed lectin (BMSL) showed a lower minimum inhibitory concentration (MIC) as compared with cN16E. BMSL-cN16E (BcN16E) exhibited strong membrane-damaging activity at a lower concentration than cN16E. Crystal violet assay showed that BcN16E inhibits mixed-species biofilm at the concentration of 15.63 µM, which is four-fold lower than the MIC. Especially, BcN16E was found to be effective in disturbing mature mixed biofilm at 31.25 µM, which is two-fold lower than the MIC, suggesting true antibiofilm activity without pressurizing the microorganisms. The treatment with BcN16E significantly reduced the exopolysaccharide synthesis (> 78%), cell surface hydrophobicity (> 70 %), hyphae formation, staphyloxanthin biosynthesis (> 41 %), and antioxidant enzyme and hemolysin activity (> 70 %). Notably, BcN16E was efficient in reducing the in vivo colonization of bacterial and fungal burden in the blood and muscle tissues of zebrafish. CONCLUSION: Antimicrobial and antibiofilm efficacy of BcN16E against MRSA, and mixed species of MRSA + CA were demonstrated. Importantly, BcN16E treatment rescued Zebrafish coinfected with mixed species of MRSA + CA. Significance and Impact of the study: The results highlight that antimicrobial loaded on lectin provides an additional advantage to recognize microorganism surface glycans and maximize drug delivery to treat polymicrobial infections caused by MRSA and CA.

Phytolectin conjugated positively charged fatty acid amide impairs virulence factors and inhibits cross-kingdom biofilm formation of Candida albicans and uropathogenic Escherichia coli.

AIM: Polymicrobial biofilm encasing cross-kingdom micro-organisms are apparent in medicine, which imposes serious resistance to conventional antimicrobial treatment. The objective of the study was to explore Butea monosperma seed lectin (BMSL) conjugated antimicrobial lipid, 2-((N-[2-hydroxyethyl]palmitamido)methyl)-1-methylpyridin-1-ium iodide (cN16E) to inhibit mixed-species biofilm of uropathogenic Escherichia coli-Candida albicans. METHODS AND RESULTS: Antimicrobial activity and antibiofilm of cN16E and cN16E-BMSL conjugate (BcN16E) were analysed against single- and mixed microbial cultures. The minimum inhibitory concentration (MIC) indicates that the MIC of cN16E-BMSL conjugate (BcN16E) against cohabiting UPEC-C. albicans was eightfold lower than the cN16E. BcN16E affects membrane integrity to elicit antimicrobial activity. BcN16E inhibits the dual-species biofilm even with 16 times lower MIC of cN16E. BcN16E impairs the biofilm-associated virulence factors which include extracellular polysaccharides, cell surface hydrophobicity, swimming, swarming motilities, hyphal filamentous morphology, curli formation and haemolysin activity. As a proof of concept, we demonstrated BcN16E ability to inhibit dual-species biofilm formation on a urinary catheter. CONCLUSION: The study revealed that the BcN16E is better than cN16E in impairing biofilm-associated virulence factors and exerting antimicrobial activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings emphasize that phytolectin has the potential to enhance the anti-virulence strategies of antimicrobials against cross-kingdom biofilm-related infections.

Phytolectin nanoconjugates in combination with standard antifungals curb multi-species biofilms and virulence of vulvovaginal candidiasis (VVC) causing Candida albicans and non-albicans Candida.

Vulvovaginal candidiasis (VVC) is a commonly occurring yeast infection caused by Candida species in women. Among Candida species, C. albicans is the predominant member that causes vaginal candidiasis followed by Candida glabrata. Biofilm formation by Candida albicans on the vaginal mucosal tissue leads to VVC infection and is one of the factors for a commensal organism to get into virulent form leading to disease. In addition to that, morphological switching from yeast to hyphal form increases the risk of pathogenesis as it aids in tissue invasion. In this study, jacalin, a phytolectin complexed copper sulfide nanoparticles (NPs) have been explored to eradicate the mono and mixed species biofilms formed by fluconazole-resistant C. albicans and C. glabrata isolated from VVC patients. NPs along with standard antifungals like micafungin and amphotericin B have been evaluated to explore interaction behavior and we observed synergistic interactions between them. Microscopic techniques like light microscopy, phase contrast microscopy, scanning electron microscopy, confocal laser scanning microscopy were used to visualize the inhibition of biofilm by NPs and in synergistic combinations with standard antifungals. Real-time PCR analysis was carried out to study the expression pattern of the highly virulent genes which are responsible for yeast to hyphal switch, drug resistance and biofilm formation upon treatment with NPs in combination with standard antifungals. The current study shows that lectin-conjugated NPs with standard antifungals might be a different means to disrupt the mixed species population of Candida spp. that causes VVC. LAY SUMMARY: The present study focuses on exploiting the high biding affinity between the cell surface glycans present in Candida cells and the plant lectin, Jacalin. Jacalin serves as a 'Trojan Horse' wherein the lectin-coupled nanoparticles show a high efficacy when compared with the unconjugated nanoparticles. The present approach also improves the anti-biofilm activity of the antifungal drugs against drug-resistant Candida strains.

Largest giant left atrium in rheumatic heart disease.

In the current era of echocardiography, early diagnosis and treatment of rheumatic heart disease make giant left atrium a rare condition, with a reported incidence of 0.3%, and following mainly with rheumatic mitral valve disease. We report a 50-year-old female, a known case of rheumatic heart disease who presented with breathlessness and dysphagia, and the cardiothoracic ratio on chest roentgenogram was 0.95. Echocardiography was suggestive of giant left atrium with a size of 19.4 x 18.3 cm, while magnetic resonance imaging revealed a size of 22.3 x 19.2 x 20.1 cm making it the largest left atrium to be reported in the literature. .

Dual Function Antimicrobial Loaded Lectin Carrier: A Strategy to Overcome Biomolecular Interference without Detectable Resistance.

The disposition of a drug in a biological system may be altered by complex biological fluids; especially, protein binding to drugs influences their activity. Herein, we demonstrated a convenient method involving the noncovalent formulation of butea monosperma seed lectin (BMSL) with an antimicrobial lipid, cationic N-acylethanolamine (cNAE) to mitigate the serum protein interference. Fluorescence spectroscopy and molecular docking study revealed that cNAEs readily formed noncovalent complexes with serum protein, bovine serum albumin. The resulting complexes interfered with the antimicrobial activity of cNAEs. Strikingly, the noncovalent conjugates developed with BMSL and cNAEs (BcNAE) overcame the interference from serum protein and displayed remarkable antimicrobial activity against uropathogenic Escherichia coli (UPEC). Strikingly, the minimum inhibitory concentration (MIC) of the lectin conjugates (7.81 µM) was 4-fold lower than the MIC of pure cNAE. Mechanistic studies showed that BcNAE depolarized the bacterial membrane and affected the integrity to exert the antimicrobial activity. The membrane directed activities of BcNAE on UPEC efficiently eliminated the development of resistance even after 25 passages. The hemocompatibility results and the biosafety assessed in a zebrafish model suggested that BcNAE was nontoxic with good selectivity to bacteria. While testing the therapeutic efficacy against UPEC infected zebrafish, we found that 1× MIC cNAE is ineffective due to interference from biological fluids, which is in agreement with in vitro studies. Remarkably, the infected fish treated with 1× MIC BcNAE conjugates were rescued from infection and restored to the normal life in less than 9 h. Bacterial colony count assay revealed that BcNAE was more efficient in overcoming the biological fluid interference and eliminated the bacterial burden in infected zebrafish. Histopathology analysis supported that BcNAE treatment restored the pathological changes induced by UPEC and, thus, increased survival. The high antimicrobial intensity with limited chance for resistance development and potential to overcome biomolecular interference with a lack of toxicity enhance the merits of exploring lectin conjugates against infectious pathogens.

Transpedal Approach in Failed Antegrade Attempt of Lower Limb Peripheral Arterial Disease-A Review with Different Treatment Strategies.

Transpedal access is an evolving technique primarily used in patients after failed femoral antegrade approach to revascularize complex tibiopedal lesions. In patients who are at high risk for surgery the transpedal access may be the only option in failed antegrade femoral access to avoid amputation of the limbs. In recent years transpedal access is used routinely to revascularize supra-popliteal lesions due to more success and less complications over femoral artery approach. Retrograde approach parse will not give success in all cases and importantly success depends on techniques used. There are different techniques that need to be used depending on lesion characteristics, comorbidities, and hardware available to improve success with less complications. This review provides different strategies for successful treatment of iliac and femoral artery lesions by transpedal approach after failed antegrade femoral attempt.

Shrimp lectin (Md-Lec) conjugated copper sulfide nanoparticles enhance the elimination of aquatic pathogens in infected Nile tilapia (Oreochromis niloticus).

Lectins are known for their ability to bind to cell surface glycans, and are useful to develop a glycan-targeted drug delivery system. This study aimed to evaluate the capacity of pectin capped copper sulfide nanoparticles (pCuS NPs) to modulate the antibacterial activity of a lectin, Md-Lec, purified from the shrimp, Metapenaeus dobsoni. Fluorescence spectroscopy revealed that Md-Lec has the ability to form a complex with pCuS NPs. Haemagglutination assay showed that the carbohydrate binding site of the lectin was preserved even after complexing with pCuS. The minimum inhibitory concentrations (MICs) obtained for Md-Lec and pCuS NPs against the tested aquatic pathogens were 50 µg ml-1 and 12.5 µM, respectively. Interestingly, the MIC of Md-Lec-pCuS NPs complex was four fold lower than that of pCuS, which was attributed to the bacterial cell surface glycan recognization activity of Md-Lec. Zone of inhibition assay showed that the zone size was highest for the lectin conjugated nanoparticles. Mechanistic study revealed that Md-Lec-pCuS NPs affect the bacterial membrane integrity and produce a large volume of reactive oxygen species to kill the bacteria. The practical aspect of using this lectin-pCuS NPs complex was evaluated by treating bacteria infected Nile tilapia (Oreochromis niloticus). The bacterial load was much less in the lectin-pCus NPs complex treated fish; moreover, the fish fully recovered from the infection. It was concluded that the conjugate of antibacterial lectin and NPs is more effective than the individual components.

Revealing the Significance of the Glycan Binding Property of Butea monosperma Seed Lectin for Enhancing the Antibiofilm Activity of Silver Nanoparticles against Uropathogenic Escherichia coli.

The incompetence of conventional antibiotics against bacteria residing in biofilms demands newer therapeutic intervention. In this study, we demonstrated that the interaction between silver nanoparticles (AgNPs) and Butea monosperma seed lectin (BMSL) forms efficient surface-functionalized AgNPs with excellent antibiofilm competency against uropathogenic Escherichia coli (UPEC). The minimum biofilm inhibitory concentration (MBIC) of AgNPs and the BMSL-AgNP conjugate (BAgNP) against UPEC was 75 and 9.37 µM, respectively. The eight-fold reduction in the MBIC of AgNPs was attributed to lectin functionalization. The chemical modification of serine amino acids affects the hemagglutination activity of BMSL but not its interaction with the AgNPs. At the same time, AgNPs surface-functionalized with modified BMSL display poor antibiofilm activity. Molecular docking studies revealed that BMSL binds to galactose with a free energy of -5.72 kcal/mol, whereas the serine residue-modified BMSL showed the lowest free energy values, suggesting incompetence for binding galactose. These results showcase that the sugar binding site of BMSL aids in the adhesion of AgNPs to the biofilm matrix and disturbs the formation of the biofilm, which was confirmed by light microscopy using crystal violet staining. At 37.5 µM, BAgNPs also have the capability to eradicate preformed biofilm. As a proof of concept, UPEC biofilm prevention and eradication were demonstrated on a urinary catheter. A scanning electron microscopy study showed that BAgNPs prevent bacterial colonization and thereby curtail biofilm growth. In addition to antibiofilm activity, BAgNPs exert antibacterial activity at 18.75 µM, which is four-fold lower than the MIC of AgNPs. A mechanistic study revealed that BAgNPs affect the integrity of the bacterial outer membrane and generate an imbalance in the antioxidant defense, which induces cell death. The results highlight that lectin functionalization can be extended to other nanoparticles and different antibiotics to enhance their efficacy against drug-resistant bacteria.

Remarkable Effect of Jacalin in Diminishing the Protein Corona Interference in the Antibacterial Activity of Pectin-Capped Copper Sulfide Nanoparticles.

Herein, we report a new strategy based on jacalin functionalization to diminish the impact of biological fluids in the antibacterial applications of nanoparticles (NPs). Precoating pectin-capped copper sulfide NPs (pCuS) with bovine serum albumin produced a protein corona, which affects the antibacterial activity of pCuS. It was found that the minimum inhibitory concentration (MIC) increases fourfold because of the formation of the protein corona. Interestingly, the pCuS functionalized with jacalin enhance the targeting capabilities through bacterial cell surface glycan recognition with no interference from the protein corona. The MIC of pCuS decreases 16-fold on functionalization with jacalin. Mechanistic studies indicated that the pCuS functionalized with jacalin impede the protein corona interference and induce bacterial cell death by impairing the GSH/reactive oxygen species balance and disrupting the bacteria cell membrane. As a proof of concept, we used a bacteria-infected zebrafish animal model to demonstrate the interference of biological fluids in the antibacterial activity of NPs. Infected zebrafish treated with 1× MIC of pCuS failed to recover from the infection, but 4× MIC rescues the fish. The requirement of a high dose of NPs to treat the infection confirms the interference of biological fluids in nanotherapeutic applications. At the same time, the jacalin-pCuS complex rescues the infected fish at 16-fold lesser MIC. The results obtained from this study suggest that jacalin-mediated NP targeting may have broad implications in the development of future nanomedicine.

Different Manifestations of Rare Cases of Unruptured Sinus of Valsalva Aneurysm-Case Series and Literature Review.

Sinus of Valsalva aneurysm (SVA) is rare, and aneurysm of the left sinus of Valsalva is extremely rare cardiovascular disease. Clinical presentation can vary from mostly asymptomatic to catastrophic life-threatening emergency. We report four extremely rare cases of SVA with different manifestations of which one case involved left aortic sinus with large unruptured aneurysm causing severe mitral regurgitation (MR) and severe aortic regurgitation (AR). The second case aneurysm was from right sinus presented with trifascicular block with intermittent complete heart block (CHB). Third was a diagnosed case of unruptured right SVA and while awaiting for surgery he had sudden cardiac death (SCD) at home. Therefore, SVA can present from asymptomatic to life-threatening condition, such as SCD. To the best of our knowledge, there are individual case reports in literature, and this is the first case series of unruptured SVA in literature highlighting the rarity of this disease.

Evaluation of the toxicities of silver and silver sulfide nanoparticles against Gram-positive and Gram-negative bacteria.

In this study, the endogenous lipid signalling molecules, N-myristoylethanolamine, were explored as a capping agent to synthesise stable silver nanoparticles (AgNPs) and Ag sulphide NPs (Ag2S NPs). Sulphidation of the AgNPs abolishes the surface plasmon resonance (SPR) maximum of AgNPs at 415 nm with concomitant changes in the SPR, indicating the formation of Ag2S NPs. Transmission electron microscopy revealed that the AgNPs and Ag2S NPs are spherical in shape with a size of 5-30 and 8-30 nm, respectively. AgNPs and Ag2S NPs exhibit antimicrobial activity against Gram-positive and Gram-negative bacteria. The minimum inhibitory concentrations (MIC) of 25 and 50 µM for AgNPs and Ag2S NPs, respectively, were determined from resazurin microtitre plate assay. At or above MIC, both AgNPs and Ag2S NPs decrease the cell viability through the mechanism of membrane damage and generation of excess reactive oxygen species.

Sub lethal levels of platinum nanoparticle cures plasmid and in combination with carbapenem, curtails carbapenem resistant Escherichia coli.

Drug resistance traits are rapidly disseminated across bacteria by horizontal gene transfer, especially through plasmids. Plasmid curing agents that are active both in vitro and in vivo will resensitize Multi Drug Resistant (MDR) bacteria to antimicrobial agents. Pectin capped platinum nanoparticles (PtNPs) at sub MIC (20 µM) concentration was effective, in causing loss of Extended Spectrum Beta Lactamase (ESBL) harboring plasmid as evidenced by, absence of plasmid in agarose gel and by a concomitant (16-64 fold) drop in MIC for cell wall inhibitors ceftriaxone and meropenem, in carbapenem resistant Escherichia coli (CREC). Interestingly, the plasmid cured strain exhibited small colony morphology and displayed slower growth both in vitro and in vivo. Complementation of cured strain with plasmid from the wild type strain restored resistance towards meropenem and ceftriaxone. Relative to wild type, plasmid cured strain displayed 50% reduction in biofilm formation. Plasmid curing also occurred in vivo in infected zebrafish with curing efficiency of 17% for nanoparticle + meropenem treatment. PtNPs + meropenem reduced bioburden of CREC in infected zebrafish by 2.4 log CFU. Mechanistic studies revealed that nanoparticle interacted with cell surface and perturbed inner membrane integrity. PtNPs did not induce ROS, yet it caused plasmid DNA cleavage, as evidenced by gyrase inhibition assay. Our study for the first time reveals that PtNPs as plasmid curing agent can resensitize MDR bacteria to selective antimicrobial agents in vivo.

Water soluble cadmium selenide quantum dots for ultrasensitive detection of organic, inorganic and elemental mercury in biological fluids and live cells.

Mercury exists in organic, inorganic, and elemental forms; all of them are highly toxic. A sensor which could detect all forms of mercury below the permissible level in environmental and biological samples would be advantageous. A facile method to synthesize N-acetyl cysteine capped cadmium selenide quantum dots (CdSe QDs) with an emission at 554 nm was reported. CdSe QDs showed high sensitivity and selectivity toward Hg in aqueous media as well as biological fluids like simulated cerebrospinal fluid, saliva, and urine, and also in natural fluids like juices of tomato, sugarcane, and lime. The sensing mechanism is attributed to the interactions between Hg and CdSe QDs inducing fluorescence quenching. The limit of detection is 1.62, 0.75, and 1.27 ppb for organic, inorganic and elemental mercury, respectively, which is below WHO guidelines. The suitability of the sensor for estimating Hg in biological fluids was demonstrated by recovery experiments. Besides sensing, a two color cell imaging method was developed employing CdSe QDs and acridine orange. Using this method, the uptake of Hg in living cells was demonstrated.

Effective elimination of biofilm formed with waterborne pathogens using copper nanoparticles.

In this paper, the self assembling properties of taurolipids were used to prepare stable copper nanoparticles (CuNPs), and demonstrated the ability of CuNPs to eradicate the biofilms formed by waterborne pathogens. The synthesized CuNPs display wine red color and exhibited surface plasmon resonance with a maximum at 590 nm. Transmission electron microscopy showed that the CuNPs are well-dispersed with spherical morphology and the size range between 5 and 12 nm. The powder X-ray diffraction study revealed that the CuNPs was free from copper oxide impurities and crystalline with the face centered cubic structure. The CuNPs exhibited excellent anti-biofilm activity against water borne pathogens such as Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, and Shigella flexneri. Light microscopy and scanning electron microscopy (SEM) study revealed that CuNPs eliminates the mature biofilm at the minimum biofilm eradication concentration of 12.5 µM. The antimicrobial activity of the CuNPs was observed at the minimum inhibitory concentration of 25 µM, indicating the reported CuNPs exhibit true anti-biofilm effect. Fluorescence microscopy and SEM study proved that CuNPs kills the bacteria through membrane damage. The possibility to use CuNPs in cleaning biofilm formed on storage containers was demonstrated through removing the mature biofilm formed on a glass pipe.

Acute effect of primary PCI on diastolic dysfunction recovery in anterior wall STEMI - A non-invasive evaluation by echocardiography.

BACKGROUND: It is well established fact that acute coronary occlusion leads to diastolic dysfunction, followed by systolic dysfunction when myonecrosis occur. It is also proven that primary percutaneous coronary intervention (PPCI) is an excellent therapy for ST elevation myocardial infarction (STEMI) to improve outcomes. However there is a paucity of information on efficacy of PPCI in improving diastolic function. Evaluation of the role of PPCI in improving diastolic dysfunction is required. METHODS: 61 patients with first anterior wall STEMI who underwent PPCI to left anterior descending artery were included. Echocardiographic evaluation was performed within 24 h of PPCI and then on day 15, 3 months and 6 months after PPCI. We evaluated the prevalence of diastolic dysfunction after PPCI and its recovery during 6 months along with effect of duration of chest pain on diastolic function. RESULTS: 54.1% of patients had diastolic dysfunction after PPCI whereas it was only 21.3% after 6 months (p value < 0.001). Diastolic function indices like deceleration time, isovolumic relaxation time, E wave, A wave, E/A ratio, left atrial volume and index improved statistically from baseline to 6 months except mitral E/e' ratio. As time required to achieve reperfusion increases (chest pain duration and D to B time) the incidence of residual diastolic dysfunction also increases (p value < 0.001). Patients with TIMI flow < III had more diastolic dysfunction (p value < 0.001). CONCLUSIONS: Primary PCI improves diastolic dysfunction in patients with anterior wall STEMI over a period of 6 months. Time to achieve reperfusion and effectiveness of reperfusion have significant effect on diastolic dysfunction.

Preparation of self-assembled platinum nanoclusters to combat Salmonella typhi infection and inhibit biofilm formation.

In this work, phytoprotein functionalized platinum nanoparticles (PtNCs) were synthesized using the proteins from fresh green spinach leaves. Transmission electron microscopy showed that PtNCs were spherical shape with size ∼5 nm, which self assembled into spherical platinum nanoclustures (PtNCs) with size within the range of 100-250 nm. The presence of elemental platinum was confirmed by EDX analysis. FTIR studies confirm that the PtNCs were stabilized by the protein. As prepared PtNCs inhibits the growth of the food borne pathogen, Salmonella typhi with minimum inhibitory concentration (MIC) of 12.5 µM. Light microscopy evidenced that the PtNCs can damage the established biofilms. Antibacterial mechanistic study revealed that PtNCs damages the S. typhi membranes, which was confirmed by scanning electron microscopy and further by fluorescence microscopy using acridine orange/propidium iodide dual staining assay. Besides membrane damage, PtNCs also triggered the intracellular ROS-mediated oxidative damage over the antioxidant defense and kills S. typhi. The hemolytic test showed low cytotoxicity of PtNCs at 100 µM (four times higher the MIC). Finally, the therapeutic efficacy of PtNCs was validated in S. typhi infected zebrafish animal model and the obtained results are discussed.