The selectivity of different external binding sites for quaternary ammonium ions in cloned potassium channels

Tetraethylammonium (TEA) is thought to be the most effective quaternary ammonium (QA) ion blocker at the external site of K⁺ channels, and small changes to the TEA ion reduce its potency. To examine the properties of the external QA receptor, we applied a variety of QA ions to excised patches from human embryonic kidney cells or Xenopus oocytes transfected with the delayed rectifying K⁺ channels Kv 2.1 and Kv 3.1. In outside-out patches of Kv 3.1, the relative potencies were TEA > tetrapropylammonium (TPA) > tetrabutylammonium (TBA). In contrast to Kv 3.1, the relative potencies in Kv 2.1 were TBA > TEA > TPA. In Kv 3.1 and Kv 2.1, external tetrapentylammonium (TPeA) blocked K⁺ currents in a fast, reversible and, in contrast to TEA, time-dependent manner. The external binding of TPeA appeared to be voltage independent, unlike the effects of TPeA applied to inside-out patches. External n-alkyl-triethylammonium compounds (C₈, C₁₀ chain length) had a lower affinity than TEA in Kv 3.1, but a higher affinity than TEA in Kv 2.1. In Kv 3.1, the decrease in QA affinity was large when one or two methyl groups were substituted for ethyl groups in TEA, but minor when propyl groups replaced ethyl groups. Changes in the free energy of binding could be correlated to changes in the free energy of hydration of TEA derivatives calculated by continuum methodology. These results reveal a substantial hydrophobic component of external QA ion binding to Kv 2.1, and to a lesser degree to Kv 3.1, in addition to the generally accepted electrostatic interactions. The chain length of hydrophobic TEA derivatives affects the affinity for the hydrophobic binding site, whereas the hydropathy of QA ions determines the electrostatic interaction energy.     

Analgesic effects of intra-muscular ketoprofen (Profenid) and pethidine for squint surgery in children

Administration of analgesics before surgery can decrease the intra-operative anesthetic requirement and pain during the early post-operative period (pre-emptive analgesia). The objective of this study was to evaluate an intra-muscular preparation of ketoprofen as analgesic in mild to moderate pain in children. In a double-blind placebo-controlled study, 91 healthy ASA I or II children undergoing squint opthalmic surgery was undertaken in the Ophthalmic Services at King Abdel-Aziz University Hospital Riyadh. The postoperative analgesic effects of intra-muscular pethidine and ketoprofen, just after the induction of anesthesia were compared. Patients were randomized to receive ketoprofen (1 mg W kg-1), pethidine (1 mg W kg-1) or saline (0.1 ml W kg-1). Anesthesia was induced and maintained with halothane and nitrous oxide via a facemask. Post-operative pain was assessed by a blinded observer using an objective pain scale. Results revealed that the ketoprofen group had lower post-operative pain scores and required less frequent analgesic therapy in the early postoperative period compared to the pethidine and placebo groups. In contrast, there were no differences in pain scores or analgesic requirements between the pethidine and the placebo groups. It is concluded that the preoperative administration of intramuscular ketoprofen, but not pethidine, provided better postoperative pain control than placebo in children undergoing ophthalmic surgery.     

Wartime determinants of arteriographically confirmed coronary artery disease in Beirut

This study investigates the association of wartime stress variables and coronary artery disease as determined by coronary angiography in Lebanon in 1986, a country with an ongoing civil war for ever a decade. A total of 127 patients who underwent coronary angiography at the American University of Beirut Medical Center were individually matched on age and sex with visitor controls free from any evidence of clinical coronary artery disease. Arteriographic cases (greater than or equal to 70% maximal stenosis) were compared with two control groups: arteriographic controls (entirely normal coronaries) and visitor controls. Findings suggest that there is a relation between exposure to both acute and chronic war events and coronary artery disease in this patient population. The reporting of exposure to acute war events was significantly higher in cases compared with both visitor controls (odds ratio (OR) = 2.4, 95% confidence interval (CI) 1.17-4.90) and arteriographic controls (OR = 2.8, 95% CI 0.93-8.47). Crossing the "green-lines" that separate two belligerent sides, considered as an attribute of war-related chronic stress, was more frequent in cases compared with visitor controls (OR = 3.25, 95% CI 1.54-6.89) and arteriographic controls (OR = 5.38, 95% CI 1.65-17.6). The relation observed between wartime stress and coronary artery disease could not be explained by possible overreporting of stressful events in patients with suspected coronary artery disease or by an increase in clinical awareness for the disease for those under continuous stress. Adjusting for the effect of the well-established coronary artery disease risk factors did not alter the above findings.     

Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma.

PURPOSE: To evaluate the safety and efficacy of fludarabine plus rituximab in treatment-naive or relapsed patients with low-grade and/or follicular non-Hodgkin's lymphoma. PATIENTS AND METHODS: This was an open-label, single-arm, single-center phase II study enrolling 40 patients. During the first week of the study, patients received two infusions of rituximab 375 mg/m2 administered 4 days apart. Seventy-two hours after the second infusion of rituximab, patients received the first of six cycles of fludarabine chemotherapy (25 mg/m2/d for 5 days on a 28-day cycle). Single infusions of rituximab were administered 72 hours before the second, fourth, and sixth cycles of fludarabine, and two infusions of rituximab were given 4 weeks after the last cycle of fludarabine. Treatment duration was 26 weeks. RESULTS: An overall response rate of 90% (80% complete response rate) was achieved in the intent-to-treat population. Similar response rates were seen in treatment-naive and previously treated patients. The median duration of response has not been reached at 40+ months. The median follow-up time in this study is 44 months (range, 15 to 66 months). In patients positive for the 14;18 translocation in blood and/or marrow at enrollment, molecular remission was achieved in 88% of cases, with patients remaining negative for up to 4 years to date. Hematologic toxicity was manageable, and except for a 15% incidence of herpes simplex/zoster infections, infectious complications were rare. Nonhematologic toxicities were minimal. CONCLUSION: Rituximab plus fludarabine was well tolerated and associated with an excellent complete response rate, including molecular remissions, in patients with low-grade or follicular lymphoma.     

Clinical and histopathological profile of primary caruncular lesions

Purpose:To provide a retrospective analysis of lesions of the caruncle which have been very rarely reported in the literature.Methods:A retrospective review of all the caruncular lesions between January 2000 and January 2020 was done at a single tertiary eye care hospital. The lesions were classified as benign and malignant lesions. Clinicopathological correlation was done for the excised lesions.Results:A total of 87 caruncular lesions were included in the study. Males (59%) were affected more than females (41%). The mean age at presentation was 44 ± 20 years. The mean duration of complaint was 36 ± 62 months. A total of 36 patients underwent surgical excision whereas the rest opted for conservative management. Recurrence was noted in five patients. Fifteen different types of lesions were identified histopathologically. Benign lesions (78%) were far more common than malignant ones (22%). Epithelial inclusion cyst was the most common benign lesion and sebaceous gland carcinoma was the most common malignant lesion. Correct clinicopathological correlation was seen in 52.7% of the cases. Caruncular tuberculosis, oncocytoma, and basosquamous cell carcinoma were some of the rare lesions.Conclusion:Caruncular lesions are uncommon and very diverse, which makes clinical diagnosis challenging. Epithelial inclusion cyst and sebaceous gland carcinoma were the most common benign and malignant lesions respectively. Correct clinicopathological correlation was seen in more than half of the cases.     

COVID-19-associated mucormycosis and treatments

In the current pandemic, COVID-19 patients with predisposing factors are at an increased risk of mucormycosis, an uncommon angioinvasive infection that is caused by fungi with Mucor genus which is mainly found in plants and soil. Mucormycosis development in COVID-19 patient is related to various factors, such as diabetes, immunocompromise and neutropenia. Excessive use of glucocorticoids for the treatment of critically ill COVID-19 patients also leads to opportunistic infections, such as pulmonary aspergillosis. COVID-19 patients with mucormycosis have a very high mortality rate. This review describes the pathogenesis and various treatment approaches for mucormycosis in COVID-19 patients, including medicinal plants, conventional therapies, adjunct and combination therapies.     

Investigation of antioxidant compounds in commercial pomegranate molasses products using matrix-solid phase dispersion extraction coupled with HPLC

Pomegranate is a well known fruit for its unique flavor, taste and health benefits. The medicinal properties of this fruits directly associated with the phenolic content present, with great anti-oxidant potential. The research is intended to develop matrix solid phase dispersion method (MSPD) and HPLC quantification of four major anti-oxidant marker constituents (vitamin C, gallic acid, rutin & ellagic acid) in pomegranate molasses samples. The effects of several important experimental parameters like type of dispersant, sample-dispersant ratio, solvents and its volume, time of extraction were investigated. A C₁₈ column with the specification (5?µm, 250?×?4.0?mm) was used for the separation. A gradient flow of mobile phase was selected after many trials containing 0.1%, v/v solution of orthophosphoric acid and acetonitrile. The flow rate was 1.0?mL/min; and the chromatograms were recorded at 254?nm. The validation parameters, like linearity (r²?=?0.9985, 0.9965, 0.9925 & 0.9986), accuracy (100.3, 99.5, 100.9 & 101.9%), intra-day precision (%RSD?=?1.09, 1.02, 1.26 & 0.97), inter-day precision (%RSD?=?1.32, 0.83, 1.07, & 1.15) LOD (0.07, 4.50, 0.45 & 0.40?µg/mL), LOQ (0.095, 9.50, 0.85 & 9.5?µg/mL) and robustness (% RSD?=?0.92, 0.76, 0.81 & 0.83) respectively for vitamin C, gallic acid, rutin & ellagic acid, were found satisfactory as per ICH guidelines.     

Gadolinium for hysterosalpingography

OBJECTIVE: To evaluate the use of gadolinium as an alternative to iodinated contrast medium for hysterosalpingography in patients with an increased risk for iodinated contrast hypersensitivity. STUDY DESIGN: Between March 2003 and March 2006, 3,616 hysterosalpingography examinations were performed. Hysterosalpingography was routinely performed using water-soluble, nonionic, iodinated contrast medium. Hysterosalpingography was performed with gadolinium in patients at risk for contrast hypersensitivity. We retrospectively reviewed the diagnostic quality, safety and clinical outcome in patients who underwent gadolinium hysterosalpingography. RESULTS: Hysterosalpingograms of diagnostic quality were successfully performed without adverse reactions in 11 patients. The density of gadolinium contrast opacification was diminished as compared with a conventional hysterosalpingogram with iodinated contrast. Two of the 8 patients who were not on oral contraceptives and had patent fallopian tubes became pregnant within 6 months of the hysterosalpingogram procedure. CONCLUSION: Gadolinium hysterosalpingography is of diagnostic value and is a safe alternative to iodinated contrast medium for hysterosalpingography in patients at increased risk for iodinated contrast hypersensitivity.     

Design optimization and efficiency enhancement of axial junction nanowire solar cells utilizing a forward scattering mechanism

We report the design, optimization, and performance analysis of three axial junction nanowire solar cells (NW SCs) based on cadmium telluride (CdTe), copper indium gallium selenide (CIGS), and copper zinc tin sulfide (CZTS) with significant improvement in their optical and electrical characteristics compared to their planar counterparts. It is shown that the performance of these NW SCs can be further improved by incorporating a hemispherical indium doped tin oxide (ITO) forward scatterer on top of the ITO front contact of the solar cells. We also compare forward scatterer incorporated NW SCs with forward scatterer incorporated planar solar cells (PSCs) and observe that forward scatterers significantly enhance the absorption in both cases. We further study the optimum size and arrangement of ITO hemispheres that result in improved photocurrent. In optimum cases, the incorporation of forward scatterers leads to absorption enhancement of 7.8%, 5.36%, and 8.8% in PSCs, and 21.4%, 7.36%, and 6.02% in NW SCs, respectively, for CdTe, CIGS, and CZTS absorbers in the same order. From the absorption profile at various wavelengths, it is found that forward scatterers enhance absorption in the 450–600 nm wavelength range, while nanowires improve absorption in the 600–800 nm range, and their combination results in an improved absorption profile for the entire visible wavelength range. We also observe increased electron–hole-pair (EHP) generation rate due to increased field-scattering and light concentration at the center of the nanowire below forward scattering hemispheres, leading to 46%, 32%, and 82.5% improvement in power conversion efficiency (PCE) for the three absorber layers, respectively. The effects of Al₂O₃ and SiO₂ passivation layers surrounding the nanowires of the optimized cells are observed, and we conclude that the CIGS absorber benefits the most when the SiO₂ passivation layer is used, increasing its PCE from 29.72% to 32.43%, while the PCEs of CdTe and CZTS are unaffected by the passivation layer due to competing effects of reduced absorption and reduced surface recombination.

We report the design and performance analysis of forward scatterer incorporated axial junction nanowire solar cells based on CdTe, CIGS, and CZTS with significant improvement in their optoelectronic properties compared to their planar counterparts.