A novel and eco-friendly procedure for the synthesis of some pyrazolo-thiadiazolo-pyrimidinones and its in vitro anti-bacterial activity

A novel series of 2-substituted-aminomethyl-8-phenyl-pyrazolo[3,4-d][1,3,4]thiadiazolo[3,2-a]pyrimidin-4(1H)-ones have been synthesized by treating 2-chloromethyl-8-phenyl-pyrazolo[3,4-d][1,3,4]thiadiazolo[3,2-a]pyrimidin-4(1H)-one with various nucleophiles. The chloromethyl derivative was prepared by treating 2-amino-3-mercapto pyrazolo[3,4-d]pyrimidine with one carbon donor, chloroacetic acid. The intermediate 2-amino-3-mercapto pyrazolo[3,4-d]pyrimidine was prepared by a novel, eco-friendly route starting from 2-amino-3-carbethoxy-1-phenyl-pyrazole. The target compounds exhibited broad-spectrum antibacterial activity (Kirby Bauer’s Method).     

Refractive surprise following implantation of correct powered intraocular lens—a real surprise!

We report a case of a 60-year-old male with unsatisfactory visual outcome following an uneventful phacoemulsification surgery for the left eye at our hospital. The evaluation of his anterior segment revealed a clear cornea, a well-positioned in-the-bag intraocular lens (IOL) and normal posterior segment. His vision in the left eye was 20/160 improving to 20/20 with +6.5?D Sphere. Repeat biometry of the left eye revealed IOL power of 22.0?D, which was same as the power of the IOL implanted during the cataract surgery. The patient underwent IOL explantation and implantation of another foldable IOL of 22.0?D. On follow-up he had an uncorrected visual acuity of 20/20. On evaluation with the Scheiner optical system, the explanted lens was found to have power of +13.92?D. This case highlights the rare possibility of postoperative refractory surprise due to incorrect labelling of the IOL by the manufacturer.     

Short-term outcome of Boston Type 1 keratoprosthesis for bilateral limbal stem cell deficiency

This study reports the short-term functional and anatomical outcome of Boston Type 1 keratoprosthesis (Boston Kpro) implantation for bilateral limbal stem cell deficiency (LCSD). Retrospective analysis was done on eight eyes of eight patients who underwent Boston Kpro implantation between July 2009 and October 2009. The best corrected visual acuity (BCVA) and slit-lamp biomicroscopy findings were assessed at 1, 3 and 6 months postoperatively. All eight eyes retained the prosthesis. BCVA of 20/40 or better was achieved in 8, 6, and 5 eyes at 1, 3, and 6 months, respectively, postoperatively. One patient each developed epithelial defect, sterile stromal melt and fungal keratitis in the late postoperative period associated with antecedent loss of the soft contact lens from the eye. Boston Kpro has good short-term visual and anatomical outcome in patients with bilateral LSCD, provided compliance with postoperative care can be ensured.     

Targeted therapy of cancer using diphtheria toxin-derived immunotoxins

The mortality rate in cancer patients demands novel therapy. One of the novel approaches developed in recent decades includes immunotoxins. Cancer cells frequently have specific growth factor receptors/antigens overexpressed on their surface; this is the principle of selective targeting of immunotoxins. Ligands recognizing these receptors and antigens can be conjugated to modified toxins. Continuous efforts are being made (i) to investigate molecules exclusively expressed on cancer cells, (ii) to improve the specificity and efficacy of these immunotoxins, (iii) to eliminate side effects (iv) to decrease immunogenicity and (v) to improve pharmacokinetics and ensure better drug delivery.     

Benefit–Risk Summary of Nivolumab for the Treatment of Patients with Unresectable Advanced,Recurrent, or Metastatic Esophageal Squamous Cell Carcinoma After Prior Fluoropyrimidine- and Platinum-Based Chemotherapy

On June 10, 2020, the U.S. Food and Drug Administration (FDA) approved nivolumab (OPDIVO; Bristol Myers Squibb, New York, NY) for the treatment of patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine‐ and platinum‐based chemotherapy. Approval was based on the results of a single, randomized, active‐control study (ATTRACTION‐3) that randomized patients to receive nivolumab or investigator''s choice of taxane chemotherapy (docetaxel or paclitaxel). The study demonstrated a significant improvement in overall survival (OS; hazard ratio = 0.77; 95% confidence interval: 0.62–0.96; p = .0189) with an estimated median OS of 10.9 months in the nivolumab arm compared with 8.4 months in the chemotherapy arm. Overall, fewer patients in the nivolumab arm experienced treatment‐emergent adverse events (TEAEs) of any grade, grade 3–4 TEAEs, and serious adverse events compared with the control arm. The safety profile of nivolumab in patients with ESCC was generally similar to the known safety profile of nivolumab in other cancer types with the following exception: esophageal fistula was identified as a new, clinically significant risk in patients with ESCC treated with nivolumab. Additionally, the incidence of pneumonitis was higher in the ESCC population than in patients with other cancer types who are treated with nivolumab. This article summarizes the FDA review of the data supporting the approval of nivolumab for the treatment of ESCC.Implications for PracticeThe approval of nivolumab for the treatment of adult patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine‐ and platinum‐based chemotherapy was based on an overall survival (OS) benefit from a randomized, open‐label, active‐controlled study called ATTRACTION‐3. Prior to this study, no drug or combination regimen had demonstrated an OS benefit in a randomized study for patients with ESCC after prior fluoropyrimidine‐ and platinum‐based chemotherapy.     

Effect of β-cyclodextrin on Rheological Properties of some Viscosity Modifiers

Cyclodextrins are a group of novel excipients, extensively used in the present pharmaceutical industry. Sometimes they show significant interactions with other conventional additives used in the formulation of dosage forms. The effect of β-cyclodextrin on the rheological properties of aqueous solutions of some selected viscosity modifiers was studied in the present work. β-cyclodextrin showed two different types of effects on the rheology of the selected polymers. In case of natural polymers like xanthan gum and guar gum, enhanced apparent viscosity was found and in case of semi-synthetic polymers like sodium carboxymethyl cellulose and methyl cellulose, reduction in apparent viscosity was found. β-cyclodextrin was included at 0.5, 1 and 2% w/v concentrations into the polymeric solutions. These findings are useful in the adjustment of concentrations of viscosity modifiers during the formulation of physically stable disperse systems.     

Outcomes of trabeculectomy in microspherophakia

Purpose:

To report the outcomes of trabeculectomy in eyes with glaucoma in microspherophakia.

Materials and Methods:

In a retrospective non-comparative case series, we analyzed 29 eyes of 18 patients with glaucoma in microspherophakia, who underwent primary trabeculectomy between 1998 and 2012. Success was defined as complete if the intraocular pressure (IOP) was ≤21 and >5 mm Hg without any antiglaucoma medication and qualified if IOP ≤21 and >5 mm Hg with or without antiglaucoma medications. Eyes not falling into qualified success criteria were labeled as failure.

Results:

The median age at the time of trabeculectomy was 23 years (inter quartile range: 12, 28). The mean IOP reduced from 31.1 ± 8.6 mm Hg to 14.6 ± 4.4 mm Hg after trabeculectomy over a median follow up of 77 months (P < 0.001). The probability of complete success was 96% (95% CI: 77-99%) at one year, 88% (95% CI: 67-96%) at 2 years, which was maintained till 7 years and decreased to 79% (95% CI: 50-92%) at 8 years. The probability of qualified success was 100% till 7 years and decreased to 90% (95% CI: 47-98%) at 8 years. The median number of postoperative medications reduced from 2 to 0 postoperatively (P < 0.001). Five eyes (21%) developed post-operative shallow anterior chamber (AC) requiring anterior chamber reformation, with 2 of these eyes needing lensectomy for resolution of this complication.

Conclusion:

Primary trabeculectomy had good success rate in glaucoma associated with microspherophakia. Post-operative shallow AC was a frequent complication needing additional intervention.