Quercetin loaded folate targeted plasmonic silver nanoparticles for light activated chemo-photothermal therapy of DMBA induced breast cancer in Sprague Dawley rats

Currently, the paucity of free drugs in conventional chemotherapy for breast-cancer curbs the desired therapeutic efficiency, often aggravating systemic toxicity. Quercetin (QRC) is a potential chemotherapeutic bio-flavonoid that is associated with poor hydrophilicity. In contrast to spherical silver nanoparticles (AgNPs), anisotropic AgNPs exhibit prominent plasmonic tunability in the near infrared (NIR) region allowing deep tissue penetration and endowing them with the ability to act as photothermal transducers as well. In this study, we optimized a simple and novel method for synthesizing folate-receptor-targeted-plasmonic silver-nanoparticles (QRC-FA-AgNPs) to serve as an efficient nanoscopic carrier system for breast cancer-cell targeted delivery of QRC and to induce photothermal therapy. A one-pot chemical synthesis method was followed for synthesizing the QRC-FA-AgNPs by finely tailoring the hydrogen bond between the reductant and stabilizer. Detailed characterization through UV-visible, near infrared (UV-vis-NIR) spectroscopy, Fourier transform infrared (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED), and energy-dispersive X-ray spectroscopy (EDX), along with particle-size, zeta-potential analysis, drug-loading and release capacity and stability studies were also performed. In vitro targeted cellular uptake, viability studies, chemo-photothermal efficacy, induction of apoptosis and the reactive oxygen species (ROS) generating potential were studied in the MDA-MB-231 cell-line and in vivo evaluation of the chemo-photothermal efficacy of QRC-FA-AgNPs was performed using a 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast-carcinogenesis model in Sprague Dawley rats. Unlike conventional AgNPs, these novel pentagonal QRC-FA-AgNPs (<50 nm) manifested a robust plasmon tunability in the NIR (>800 nm) region. Detailed in vitro and in vivo studies revealed their active role in improving breast-cancer conditions by allowing controlled and targeted discharge of QRC at the tumor site, along with evoking hyperthermia under NIR laser irradiation that induced selective ablation of cancer cells. Following successful cellular internalization, the photothermal efficacy of QRC-FA-AgNPs supplemented their chemotherapeutic potency, allowing apoptosis and restraining the tumor growth. This current study highlighted the augmented efficacy of plasmonic QRC-FA-AgNPs in comparison to free quercetin, thus the development of a potential nanocarrier based on the pleiotropic function of plasmonic AgNPs may provide an efficient combined chemo-photothermal based strategy for the assassination of breast-cancer cells.

Novel plasmonic (>800 nm) pentagonal QRC-FA-AgNPs synthesized through simple chemical technique induces light activated combined chemo-photothermal efficacy against breast cancer.     

Development of amino acid conjugated sulfonamides as potent antiulcer agent

A series of 2-{[(4-methylphenyl) sulfonyl] amino}-3-sulfanylpropanoic acid (1a) and its analogs 1b–j have been synthesized. These compounds were screened for their in vivo efficacy in pyloric ligation model. Compounds 1a and 1b with higher antiulcer potential were further screened in other gastric models to explore the mode of antiulcer action. To further understand the mode of action, in vitro inhibition of H⁺/K⁺ ATPase activity in gastric microsome isolated from rat stomach was studied. This was rationalized by in silico experiments.     

Diagnostic yield and therapeutic impact of novel motorized spiral enteroscopy in small-bowel disorders: a single-center,real-world experience from a tertiary care hospital (with video)

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Transcatheter embolization of uterine arteriovenous malformation: report of 2 cases and review of literature

Arteriovenous malformation (AVM) of the uterus is a rare cause of menorrhagia and may at times lead to life-threatening hemorrhage. The clinical findings may not always be reliable in the diagnosis of uterine AVM, and a high index of suspicion is important because, unlike many other causes of menorrhagia, curettage may paradoxically aggravate the bleeding. Herein are described the cases of 2 patients with uterine AVM with abnormal vaginal bleeding. Both had a history of abortion followed by dilation and curettage. In both patients, the diagnosis of uterine AVM was established at Doppler flow ultrasonography. Treatment using transcatheter embolization was successful, and both patients had normal menstrual cycles at follow-up. One patient delivered a healthy baby 2? years after transcatheter embolization.     

Regurgitation on pressure over the lacrimal sac versus lacrimal irrigation in determining lacrimal obstruction prior to intraocular surgeries

Purpose:To determine the diagnostic accuracy of manual regurgitation on pressure over the lacrimal sac (ROPLAS) versus lacrimal irrigation for screening nasolacrimal duct obstruction (NLDO) in adults prior to intraocular surgeries.Methods:This cross-sectional study took place in a tertiary eye care hospital in South Tamil Nadu, India. From January to December 2017 and included consecutive patients who presented for routine cataract surgery. Prospective data collection occurred in 8369 eyes of patients who underwent cataract surgery. All patients underwent ROPLAS testing by an ophthalmologist followed by lacrimal irrigation by trained ophthalmic assistants, rechecked or confirmed in equivocal cases by ophthalmologists who were masked to the ROPLAS status. The primary outcome, the sensitivity, specificity, positive, and negative predictive values to detect lacrimal occlusion by ROPLAS compared with lacrimal irrigation with 95% confidence intervals was estimated.Results:A total of 8369 eyes underwent cataract surgery during the time periods of the study. ROPLAS and lacrimal irrigation were performed in all eyes. The sensitivity of ROPLAS to diagnose NLDO correctly was 54.5% (95% CI, 44.8%–63.9%) and its specificity was 100% (95% CI, 100%–100%). The positive and negative predictive values were 75.3% (95% CI, 65.6%-83.0%) and 99.4% (95% CI, 99.2%–99.5%), respectively.Conclusion:We found that ROPLAS when used alone had very low sensitivity and low positive predictive value in detecting NLDO prior to cataract surgery as compared with lacrimal irrigation. Hence, we recommend performing ROPLAS and lacrimal irrigation in every patient as part of the routine preoperative workup prior to cataract surgery.     

Functional and anatomic outcome of scleral buckling versus primary vitrectomy in pseudophakic retinal detachment

PURPOSE: To conduct a randomized prospective clinical trial to compare primary vitrectomy without scleral buckling versus conventional scleral buckling surgery in pseudophakic primary retinal detachment (PPRD) in terms of anatomic attachment rate, functional outcome and complications. METHODS: Fifty consecutive eyes of 50 patients with PPRD were randomized into two groups, with 25 patients in each of group 1 (scleral buckling group) and group 2 (pars plana vitrectomy without buckling group) in a hospital setting and followed up at 1 week, 2 weeks, 6 weeks and 6 months. RESULTS: A primary reattachment rate of 76% (19 retinas) was obtained in group 1, while a reattachment rate of 84% (21 retinas) was achieved in group 2. The final anatomic reattachment rate was 100% in both groups. The causes of failure in group 1 were proliferative vitreoretinopathy in five eyes and open break/missed break in one eye. The causes of failure in group 2 were missed break/open break in three eyes and proliferative vitreoretinopathy in one eye. Best corrected visual acuity (BCVA) at 2 weeks was better in group 1, while the final BCVA at end of 6 months was two lines better in group 2. The mean change in refractive error was -- 1.38 D in group 1 and -- 0.85 D in group 2. CONCLUSIONS: Pars plana vitrectomy without buckling provides an effective treatment for PPRD and results in better longterm visual and anatomic outcomes than conventional scleral buckling.