Potent antimicrobial action of triclosan–lysozyme complex against skin pathogens mediated through drug-targeted delivery mechanism

Triclosan (TCS), an antimicrobial agent that inhibits bacterial fatty acid synthesis by blocking the active site of enoyl-ACP reductase (FabI), is a water-insoluble agent that limits its therapeutic candidacy. We have recently shown that the water solubility and antimicrobial activity of TCS were greatly enhanced when complexed to lysozyme (LZ). This study is to examine the therapeutic potential of triclosan–lysozyme (T–LZ) complex against common skin pathogens expressing different levels of FabI, and to delineate the drug-targeting mechanism by lysozyme. The T–LZ exhibited superior antimicrobial activity against two bacterial skin pathogens, Propionibacterium acnes and Corynebacterium minutissimum, while yeast pathogens, Candida albicans and Malassezia furfur lacking FabI enzyme were insensitive to the complex. Unlike free TCS or LZ, the T–LZ complex exhibited a potent antibacterial activity under a wide range of pH condition and salt concentration. Interestingly, P. acnes expressing greater amount of FabI was more susceptible to the T–LZ complex than C. minutissimum that produces lesser amount of the enzyme. A sensitive assay of FabI activity revealed that P. acnes and C. minutissimum treated with the complex exhibited significant inhibition of the intracellular FabI activity than cells treated with free TCS, indicating the efficiency of lysozyme to specifically deliver TCS to its target (FabI) in the cytoplasm of bacterial cells. These results demonstrate, for the first time, that lysozyme is a potential drug carrier that allows specific targeting to the microbial cells of the water-insoluble triclosan and highlights the potency of the complex for the treatment of skin bacterial infections.     

Preparation of a novel floating ring capsule-type dosage form for stomach specific delivery

Study objectives were to develop a unique floating ring capsule dosage form which combines gastric soluble and insoluble portions, and to evaluate its suitability for stomach specific drug delivery. New floating ring capsules were developed using different polymers and were compared for various parameters. The formulation with HPMC and sodium CMC has better floating properties. The effects of polymers concentration on drug release were studies by in vitro release studies. The interaction studies of combined drug with polymers were determined using FT-IR spectroscopy. The entrapped air within the gel barrier and lower densities of HPMC and sodium CMC resulted in better floating behavior. Steady slow gel formations showed prolonged drug release. The in vitro release rates were generally found to be faster with low concentration of carbopol showing release within 2 h, while formulations containing high amount of HPMC showed release in 8 h. In particular, the higher concentration of HPMC formulation shows the best drug release performance. A very low change in peak shift was observed only with sodium alginate formulations. Further, FT-IR measurements confirmed the absence of any chemical interactions. Results indicate that new floating ring capsule is a promise dosage form for stomach specific delivery.     

p53 and P-glycoprotein expression do not correlate with survival in nonsmall cell lung cancer: a long-term study and literature review.

This long-term study includes up to 13 years of follow-up on 56 patients who underwent surgical resection of nonsmall cell lung cancers (NSCLC) at the University of Texas Medical Branch. The purpose of this study was to investigate whether p53 and P-glycoprotein expression in the tumor correlates with survival. The study included 35 men and 21 women with mean age at diagnosis of 63.6 years and 58.0 years, respectively. Follow-up ranged from four to 156 months (mean, 52 mo). Actual five-year survival was 50% and 10-year survival was 22%. There were 25 patients who survived more than 60 months. Commercially available antibodies, DO-7 monoclonal antibody to p53 protein, and NCL-PGLyp polyclonal antibody to P-glycoprotein were used. p53 expression was seen in 45%, and P-glycoprotein expression was seen in 61% of the tumors, using standard immunohistochemical techniques. Expression of p53 showed correlation with Caucasian race and a better, although nonsignificant, five-year survival. P-glycoprotein expression showed a highly significant association with squamous cell carcinoma. No association was found between P-glycoprotein expression and survival. A negative association was seen between p53 and P-glycoprotein expression. Using nonparametric analysis, significant correlations were found between female sex and younger age at diagnosis of lung cancer compared with males, adenocarcinoma, and Caucasian race. Using Kaplan-Meier survival tables, significantly better five-year survival was seen with stage I tumors, negative lymph nodes at surgery, Caucasian race, and well-differentiated tumors. Stage I and negative lymph nodes at surgery showed an independent significant association with long-term (>5-yr) survival. This study indicates that p53 and P-glycoprotein may not be useful as immunohistochemical markers for guiding therapy and predicting survival in NSCLC.     

Measuring hypomania in the postpartum: a comparison of the Highs Scale and the Altman Mania Rating Scale

We examine the prevalence of hypomania on day 3 postpartum using two self-report mania scales: The Highs Scale and Altman Mania Rating Scale (AMRS). 279 women were recruited from postnatal wards and completed the questionnaires on day 3 postpartum. The scales show good correlation, however, 11% of women meet the suggested threshold for caseness on the Highs Scale and 44% on the AMRS. Hypomanic symptoms are commonly experienced in the early postpartum. Although there is some evidence that the Highs Scale might be conservative, the AMRS likely overestimates hypomania in the postpartum. The definition of what constitutes ‘a case’ of postnatal hypomania requires further validation against clinical interview and ability to predict variables of clinical importance. Mania scales developed in bipolar disorder populations must be specifically validated for postpartum use.     

Miller Fisher syndrome after COVID-19 vaccination: Case report and review of literature

Rationale:Miller Fisher syndrome (MFS) is a rare variant of Guillain-Barre syndrome, classically diagnosed based on the clinical triad of ataxia, areflexia, and ophthalmoplegia. MFS is usually preceded by viral infections and febrile illness; however, only a few cases have been reported after vaccinations.Patient concerns:A 53-year-old hypertensive male presented with a 2-day history of progressive ascending paralysis of the lower limbs along with diplopia and ataxia, 8 days after the first dose of the Sinovac–Coronavac coronavirus disease 2019 (COVID-19) vaccination, with no prior history of any predisposing infections or triggers.Diagnoses:Physical examination showed moderate motor and sensory loss with areflexia in the lower limbs bilaterally. Routine blood investigations and radiological investigations were unremarkable. Cerebrospinal fluid analysis showed albuminocytologic dissociation and nerve conduction studies revealed prolonged latencies with reduced conduction velocities. The diagnosis of MFS was established based on the findings of physical examination, cerebrospinal fluid analysis, and nerve conduction studies.Interventions:A management plan was devised based on intravenous immunoglobulins, pregabalin, and physiotherapy. However, due to certain socioeconomic factors, the patient was managed conservatively with regular physiotherapy sessions.Outcomes:Follow-up after 6 weeks showed remarkable improvement, with complete resolution of symptoms 10 weeks after the discharge.Lessons:This case suggests that MFS is a rare adverse effect after COVID-19 vaccination and additional research is required to substantiate a temporal association. Further studies are needed to understand the pathophysiology behind such complications to enhance the safety of COVID-19 vaccinations in the future.     

Electric-Field-Coupled Resonator Antenna for 5G Applications

In this paper, a compact wideband patch antenna comprising a modified electric-field-coupled resonator with parasitic elements is presented. The resonance at low frequency is achieved due to the electric field polarization along the split of the conventional LC (inductive-capacitive) structure. However, this antenna gives low bandwidth as well as low gain. Some evolutionary techniques are adopted to get a compact wideband antenna at 3GPP bands of 5G. The split width and the ground plane are modified to achieve enhanced bandwidth with good impedance matching, whereas the addition of the parasitic elements on both sides of the microstrip feed line enhances the gain with a slight reduction of bandwidth. The compact dimension of the proposed antenna is 0.26 λ_L × 0.26 λ_L × 0.017 λ_L, where λ_L is the free space wavelength at the lowest frequency. A prototype of the presented design is fabricated and measured. Measurement shows that the antenna has an operating bandwidth of 19.74% for |S11| < −10 dB where the gain of 1.15 dBi is realized. In addition, the radiation pattern is omnidirectional in the horizontal plane and dumbbell shaped in the elevation plane. The cross-polarization levels in both planes are less than −12 dB.     

Extraction of Natural Dye from Aerial Parts of Argy Wormwood Based on Optimized Taguchi Approach and Functional Finishing of Cotton Fabric

The aerial parts of the Argy Worm Wood (AWW) plant have been used in different Chinese foods as a colorant and a taste enhancer for a long time. Despite its application as a food colorant, it has rarely been considered for the coloration of textiles. Keeping in mind the variation in color strength due to the change in phytochemical contents by seasonal change and other variables, the extraction of AWW aerial parts was optimized using the Taguchi method. Optimization was performed on the basis of total phytochemical contents (phenols, flavonoids, and tannins) in the extracted solutions. For this purpose, two different solvent systems, namely sodium hydroxide/water (NaOH/water) and ethanol/water (EtOH/water), were applied through a simple aqueous extraction method at varying levels of solvent concentration, and extraction temperature and duration. Maximum phytochemicals yield of 21.96% was obtained using NaOH/water system with 9 g/L NaOH/water at 85 °C for 20 min and 25.5% with 75% aqueous ethanol at 85 °C for 40 min. Optimized extracts were characterized by UV-Vis and FTIR spectrophotometry, which showed the presence of multiple phytochemicals in the extracts. The dyeing temperature and time were also optimized. Dyed cotton fabrics showed medium to high colorfastness to washing and excellent antibacterial and UV radiation absorption properties. The effect of pre-mordanting with salts of iron and copper was also studied on the color fastness properties. Cotton fabrics dyed with two different solvent system extracts displayed various shades of brown with NaOH/water, and green with aqueous ethanol with and without pre-mordanting. The present study provides the textile industry with a promising source of functional bio-colorant and a value-adding approach for the AWW plant industry.     

Corticospinal function in severe brain injury assessed using magnetic stimulation of the motor cortex in man.

We have assessed corticospinal function in 19 post-coma patients severely brain-injured by anoxia or physical trauma. Eleven patients were unresponsive (Category 1) and eight demonstrated minimal, non-verbal responses to simple commands (Category 2). Motor evoked potentials (MEPs) could be elicited in hand and leg muscles in nine Category 1 and all eight Category 2 patients in response to transcranial magnetic stimulation (TMS). In comparison with normal subjects, threshold to TMS was significantly elevated in Category 1 but not in Category 2. Central conduction times were within the normal range except for two patients (one in each category) in whom they were prolonged. The variability in MEP amplitude to constant TMS was not significantly different from normal in either category. The size of MEPs recorded simultaneously in different hand muscles were correlated in all three groups. The presence of H-reflexes in hand muscles was associated with an absence of MEPs or a high threshold to TMS. Variability of MEPs was substantially greater than that of H-reflexes. We conclude that brain injury of a severity that may preclude consciousness and voluntary movement does not invariably predicate a non-functional motor cortex and corticospinal system.