Diagnostic accuracy of tongue swab testing on two automated tuberculosis diagnostic platforms, Cepheid Xpert MTB/RIF Ultra and Molbio Truenat MTB Ultima.

Tongue dorsum swabbing is a potential alternative to sputum collection for tuberculosis (TB) testing. Previous studies showed that Cepheid Xpert MTB/RIF Ultra (Xpert Ultra) can detect Mycobacterium tuberculosis DNA on tongue swabs stored in buffer, with 72% sensitivity and 100% specificity relative to a sputum microbiological reference standard (sputum MRS). The present study evaluated a more convenient sample collection protocol (dry swab storage), combined with streamlined sample processing protocols, for evaluating two commercial TB diagnostic tests: Xpert Ultra and Molbio Truenat MTB Ultima (MTB Ultima). Copan FLOQSwabs were self-collected or collected by study workers from 321 participants in Western Cape, South Africa. All participants had symptoms suggestive of TB, and 245 of them had sputum MRS-confirmed TB (by sputum MGIT culture and/or Xpert Ultra). One tongue swab per participant was tested on Xpert Ultra, and another tongue swab was tested with MTB Ultima. Xpert Ultra was 75.5% sensitive and 100% specific relative to sputum MRS, similar to previous methods that used swabs stored in buffer. MTB Ultima was 71.6% sensitive and 96.9% specific relative to sputum MRS. When sample lysates that were false-negative or invalid by MTB Ultima were frozen, thawed, and re-tested, MTB Ultima sensitivity rose to 79.1%. Both tests were more sensitive with swabs from participants with higher sputum Xpert Ultra semi-quantitative results. Although additional development could improve diagnostic accuracy, these results further support tongue swabs as easy-to-collect samples for TB testing. IMPORTANCE: Tongue dorsum swabbing is a promising alternative to sputum collection for tuberculosis (TB) testing. Our results lend further support for tongue swabs as exceptionally easy-to-collect samples for high-throughput TB testing.

Tongue swab testing on two automated tuberculosis diagnostic platforms, Cepheid Xpert® MTB/RIF Ultra and Molbio Truenat® MTB Ultima.

Tongue dorsum swabbing is a potential alternative to sputum collection for tuberculosis (TB) testing. Previous studies showed that Cepheid Xpert® MTB/RIF Ultra (Xpert Ultra) can detect Mycobacterium tuberculosis (MTB) DNA in tongue swabs stored in buffer, with 72% sensitivity and 100% specificity relative to a sputum microbiological reference standard (sputum MRS). The present study evaluated a more convenient sample collection protocol (dry swab storage), combined with streamlined sample processing protocols, for side-by-side analysis using two commercial TB diagnostic tests: Xpert Ultra and Molbio Truenat® MTB Ultima (MTB Ultima). Copan FLOQSwabs were self-collected, or collected by study workers, from 321 participants in Western Cape, South Africa. All participants had symptoms suggestive of TB, and 245 of them had sputum MRS-confirmed TB (by sputum culture and/or Xpert Ultra). One tongue swab per participant was tested on Xpert Ultra and another tongue swab was tested with MTB Ultima. Xpert Ultra was 75.4% sensitive and 100% specific, and MTB Ultima was 71.6% sensitive and 96.9% specific, relative to sputum MRS. When sample lysates that were false-negative by MTB Ultima were frozen, thawed, and re-tested, MTB Ultima sensitivity rose to 79.1%. Both tests were more sensitive with swabs from participants with higher sputum Xpert semi-quantitative results. The protocol for Xpert Ultra enabled fast and easy testing of dry-stored swabs with no loss of accuracy relative to previous methods. MTB Ultima testing of dry-stored swabs exhibited comparable performance to Xpert Ultra. These results further support tongue swabs as easy-to-collect samples for high-throughput TB testing.

Prevention of chemotherapy toxicity by agents that neutralize or degrade cell-free chromatin.

BACKGROUND: Toxicity associated with chemotherapy is a major therapeutic challenge and is caused by chemotherapy-induced DNA damage and inflammation. We have recently reported that cell-free chromatin (cfCh) fragments released from dying cells can readily enter into healthy cells of the body to integrate into their genomes and induce DNA double-strand breaks, apoptosis and inflammation in them. We hypothesized that much of the toxicity of chemotherapy might be due to release of large quantities of cfCh from dying cells that could trigger an exaggerated DNA damage, apoptotic and inflammatory response in healthy cells over and above that caused by the drugs themselves. METHODS: We tested this hypothesis by administering cfCh neutralizing/degrading agents namely, anti-histone antibody complexed nanoparticles, DNase I and a novel DNA degrading agent-Resveratrol-Cu concurrently with five different chemotherapeutic agents to examine if chemotherapy-induced toxicity could be minimized. RESULTS: We observed (i) significant reduction in chemotherapy-induced surge of cfCh in blood; (ii) significant reduction in chemotherapy-induced surge of inflammatory cytokines CRP, IL-6, IFNγ and TNFα in blood; (iii) abolition of chemotherapy-induced tissue DNA damage (γH2AX), apoptosis (active caspase-3) and inflammation (NFκB and IL-6) in multiple organs and peripheral blood mononuclear cells; (iv) prevention of prolonged neutropenia following a single injection of adriamycin and (v) significant reduction in death following a lethal dose of adriamycin. CONCLUSION: Our results suggest that toxicity of chemotherapy is caused to a large extent by cfCh released from dying cells and can be prevented by concurrent treatment with cfCh neutralizing/degrading agents.

Biodegradable anionic acrylic resin based hollow microspheres of moderately water soluble drug rosiglitazone maleate: preparation and in vitro characterization.

BACKGROUND: Most of floating systems have an inbuilt limitation of high variability in the gastric retention time, invariably affecting the bioavailability of drug. An oral sustained release system is formulated to increase gastric residence time by a different way like floating. AIM: The objective of present investigation was to prepare hollow microspheres of Rosiglitazone Maleate in order to increase its bioavailability and reduce the dose frequency. METHOD: Hollow microspheres of Rosiglitazone Maleate were prepared by O/W emulsion-solvent diffusion technique using biodegradable anionic acrylic resin as a polymer. A mixture of dichloromethane and ethanol (1:1) used as solvent system for drug and polymer with water containing polyvinyl alcohol and salt as external aqueous phase. RESULT: Entrapment efficiency of drug was increased upto 89.71% as a result of salting out effect. The morphology of Eudragit S100 based microspheres in comparison to Ethyl cellulose and hydroxy propyl methyl cellulose (HPMC) was found to be hollow, spherical, and porous which was analysed by scanning electron microscopy. Microspheres were evaluated for micromeritic profile and found satisfactory. The FT-IR spectra confirmed the absence of drug-polymer interaction. The Eudragit S100 based formulation demonstrated favorable in vitro floating and sustained release profile for longer period of time with increased bioavailability. The anionic acrylic resin based microspheres confirmed to have high floating ability >12 h. CONCLUSION: Entrapment efficiency and bioavailability of Rosiglitazone Maleate loaded microspheres were increased significantly after modification of method. The release mechanism for formulation was diffusion controlled and had followed first order kinetics, as well as physically and chemically stable as per ICH guidelines.

A multi-centre comparative study of diclofenac sodium and a dipyrone/spasmolytic combination, and a single-centre comparative study of diclofenac sodium and pethidine in renal colic patients in India.

A single-blind, randomized clinical trial was carried out to compare the analgesic effectiveness in patients with renal colic of single intramuscular doses of diclofenac sodium (75 mg) versus a dipyrone (1 g)/spasmolytics combination, and diclofenac sodium (75 mg) versus pethidine (75 mg). The first study involved three centres, the second study one centre. In total, 107 patients were treated with diclofenac sodium, 85 with dipyrone/spasmolytics, and 25 with pethidine. Assessments were made during the first hour after drug administration of the degree of pain relief, the severity of pain using a visual analogue scale, and the duration of analgesia. A global assessment of treatment efficacy was made by the participating physicians at the end of the study period. Patients treated with diclofenac sodium showed an earlier onset of analgesia and a higher incidence of total pain relief compared to those treated with dipyrone/spasmolytics or pethidine. Although the mean duration of analgesia was only slightly greater in the diclofenac sodium group than in the dipyrone/spasmolytics group, a significantly longer effect was seen when diclofenac sodium was compared with pethidine (p less than 0.01). Pain severity assessments revealed that diclofenac sodium caused a significantly greater improvement in pain after 60 minutes compared to dipyrone/spasmolytics (p less than 0.05) and after 30 minutes compared to pethidine (p less than 0.05). Global efficacy assessments by the physician rated diclofenac sodium as significantly superior to dipyrone/spasmolytics (p less than 0.01) and pethidine (p less than 0.001). Moreover, diclofenac sodium was better tolerated than either of the comparative treatments. The results indicate that intramuscular diclofenac sodium is a useful alternative to the drugs commonly used in India in the treatment of renal colic.