Evaluation of the Influence of Zhenwu Tang on the Pharmacokinetics of Digoxin in Rats Using HPLC-MS/MS

Digoxin (DIG) is a positive inotropic drug with a narrow therapeutic window that is used in the clinic for heart failure. The active efflux transporter of DIG, P-glycoprotein (P-gp), mediates DIG absorption and excretion in rats and humans. Up to date, several studies have shown that the ginger and Poria extracts in Zhenwu Tang (ZWT) affect P-gp transport activity. This study aimed to explore the effects of ZWT on the tissue distribution and pharmacokinetics of DIG in rats. The deionized water or ZWT (18.75 g/kg) was orally administered to male Sprague–Dawley rats once a day for 14 days as a pretreatment. On day 15, 1 hour after receiving deionized water or ZWT, the rats were given the solution of DIG at 0.045 mg/kg dose, and the collection of blood samples was carried out from the fundus vein or excised tissues at various time points. HPLC-MS/MS was used for the determination of the DIG concentrations in the plasma and the tissues under investigation. The pharmacokinetic interactions between DIG and ZWT after oral coadministration in rats revealed significant reductions in DIG Cmax and AUC0-∞, as well as significant increases in T1/2 and MRT0-∞. When coadministered with ZWT, the DIG concentration in four of the investigated tissues statistically decreased at different time points except for the stomach. This study found that combining DIG with ZWT reduced not only DIG plasma exposure but also DIG accumulation in tissues (heart, liver, lungs, and kidneys). The findings of our study could help to improve the drug's validity and safety in clinical applications and provide a pharmacological basis for the combined use of DIG and ZWT.

Case Report: Osteomyelitis of the Proximal Phalanx of the Finger in Patient With Ollier Disease

Ollier disease is a rare congenital pathology characterized by the growth of enchondromas in bones, accompanied with their deformities, fractures, and the risk of malignancy. A 39-year-old patient with Ollier disease (acroform with lesions of hands and feet) suffered a rapid development of osteomyelitis of the proximal phalanx of the ring finger after a mosquito bite. The condition localized in the area of enchondroma. Surgical treatment included osteonecrectomy in the phalanx and enchondroma with excision of non-viable surrounding soft tissues, drainage of the surgical wound and the imposition of primary sutures. Morphological analysis confirmed the presence of ectopic embryonic cartilage specific for Ollier disease and the bone destruction. The excised tissues were infiltrated with immune cells and had signs of periosteal chronic inflammation including fibrosis and hyalinosis. These changes, which occurred long before the mosquito bite, became a favorable background for the development of a purulent infection.

Evaluation of the Factors Affecting the Cure Rate of Cervical Intra-Epithelial Neoplasia Recurrence Using Defective Models

Background: Treatment of cervical intraepithelial neoplasia is very important since if it remains untreated, it may progress to cervical cancer. It is usually treated with excisional surgery. This study aimed to find the factors affecting the cure rate of cervical intraepithelial neoplasia recurrence after surgery using defective models. Study design: A retrospective cohort study. Methods: Excisional surgery was performed on 307 patients with high-grade cervical intraepithelial neoplasia, from 2009 to 2017. The patients were followed up until recurrence based on histopathology report. Hematologic factors were measured before surgery. The cure rates were estimated using defective models with a Gamma frailty term and the results were compared. Results: Neutrophil-to-lymphocyte ratio (NLR) (P<0.001) and excised mass size (P<0.001) had significant impacts on cure rates, and their cut-off values were 1.9 (P<0.001) and 15 mm2 (P<0.001), respectively. Patients with lower neutrophil-to-lymphocyte ratios and larger excised tissues had higher cure rates. Defective 3-parameter Gompertz distribution with gamma frailty term had the best fit to the data, and its estimated cure rates were 98% among patients with an excised mass size of >15 mm2 and NLR of <1.9, 84% among patients with an excised mass size of >15 mm2 and NLR of >1.9, 79% among patients with an excised mass size of <15 mm2 and NLR of <1.9, and 30% among patients with an excised mass size of <15 mm2 and NLR of >1.9. Conclusion: Cervical intraepithelial neoplasia must be identified and treated before its progress. Excision of more tissues during excisional surgery, especially when the NLR of the patient is high, can help to prevent cervical intraepithelial neoplasia recurrence.

Multi-modal nonlinear optical and thermal imaging platform for label-free characterization of biological tissue

The ability to characterize the combined structural, functional, and thermal properties of biophysically dynamic samples is needed to address critical questions related to tissue structure, physiological dynamics, and disease progression. Towards this, we have developed an imaging platform that enables multiple nonlinear imaging modalities to be combined with thermal imaging on a common sample. Here we demonstrate label-free multimodal imaging of live cells, excised tissues, and live rodent brain models. While potential applications of this technology are wide-ranging, we expect it to be especially useful in addressing biomedical research questions aimed at the biomolecular and biophysical properties of tissue and their physiology.

How Do Marine Mammals Manage and Usually Avoid Gas Emboli Formation and Gas Embolic Pathology? Critical Clues From Studies of Wild Dolphins

Decompression theory has been mainly based on studies on terrestrial mammals, and may not translate well to marine mammals. However, evidence that marine mammals experience gas bubbles during diving is growing, causing concern that these bubbles may cause gas emboli pathology (GEP) under unusual circumstances. Marine mammal management, and usual avoidance, of gas emboli and GEP, or the bends, became a topic of intense scientific interest after sonar-exposed, mass-stranded deep-diving whales were observed with gas bubbles. Theoretical models, based on our current understanding of diving physiology in cetaceans, predict that the tissue and blood N2 levels in the bottlenose dolphin (Tursiops truncatus) are at levels that would result in severe DCS symptoms in similar sized terrestrial mammals. However, the dolphins appear to have physiological or behavioral mechanisms to avoid excessive blood N2 levels, or may be more resistant to circulating bubbles through immunological/biochemical adaptations. Studies on behavior, anatomy and physiology of marine mammals have enhanced our understanding of the mechanisms that are thought to prevent excessive uptake of N2. This has led to the selective gas exchange hypothesis, which provides a mechanism how stress-induced behavioral change may cause failure of the normal physiology, which results in excessive uptake of N2, and in extreme cases may cause formation of symptomatic gas emboli. Studies on cardiorespiratory function have been integral to the development of this hypothesis, with work initially being conducted on excised tissues and cadavers, followed by studies on anesthetized animals or trained animals under human care. These studies enabled research on free-ranging common bottlenose dolphins in Sarasota Bay, FL, and off Bermuda, and have included work on the metabolic and cardiorespiratory physiology of both shallow- and deep-diving dolphins and have been integral to better understand how cetaceans can dive to extreme depths, for long durations.

Plasticity of body axis polarity in Hydra regeneration under constraints

One of the major events in animal morphogenesis is the emergence of a polar body axis. Here, we combine classic grafting techniques with live imaging to study the emergence of body axis polarity during whole body regeneration in Hydra. Composite tissues are made by fusing two rings, excised from separate animals, in different configurations that vary in the relative polarity and original position of the rings along the body axis of the parent animals. We find that under frustrating initial configurations, body axis polarity that is otherwise stably inherited from the parent animal, can become labile and even be reversed. The site of head regeneration exhibits a bias for the edges of the fused doublets, even when this involves polarity reversal in the tissue, emphasizing the importance of structural factors in head formation. The doublets’ edges invariably contain defects in the organization of the supra-cellular actin fibers, which form as the tissue ring seals on each side. We suggest that the presence of a defect can act as an “attractor” for head formation at the edge, even though a defect is neither required nor sufficient for head formation. The observation of head formation at an originally distal edge of the tissue upon polarity reversal, is not compatible with models of Hydra regeneration based solely on preexisting morphogen gradients. Rather, our results suggest that body axis determination is a dynamic process that involves mechanical feedback and signaling processes that are sensitive to the original polarity and position of the excised tissues.Significance statementThe formation of a polar body axis is one of the most basic steps in defining the body plan of a developing animal. Here we study the emergence of polarity in Hydra regenerating from composite tissue segments under constraints. We show that these frustrating conditions expose non-trivial dynamics, reflecting the integration of the memory of the tissue’s original polarity and position in the parent animal with dynamic biochemical and mechanical processes. In particular, we demonstrate that the organization of the cytoskeleton participates together with biochemical signaling processes in feedback loops that eventually result in the formation and stabilization of the animal’s body axis. We conclude that preexisting biochemical gradients in the tissue cannot by themselves explain axis determination.

Direct Molecular Analysis of In Vivo and Freshly Excised Tissues in Human Surgeries with the MasSpec Pen Technology

Intraoperative tissue analysis is critical to guide surgical procedures and improve patient outcomes. Here, we describe the clinical translation and intraoperative use of the MasSpec Pen technology for direct molecular analysis of in vivo and freshly excised tissues in the operating room. In this study, the MasSpec Pen was used by surgeons and surgical staff during 100 surgeries over a 12-month period, allowing rapid detection of rich mass spectral profiles from 715 in vivo and ex vivo analyses performed on thyroid, parathyroid, lymph node, breast, pancreatic, and bile duct tissues during parathyroidectomies, thyroidectomies, breast, and pancreatic neoplasia surgeries. The MasSpec Pen enabled gentle extraction and sensitive detection of various molecular species including small metabolites and lipids using a droplet of sterile water without causing apparent tissue damage. Notably, effective molecular analysis was achieved while no limitations to sequential histologic tissue analysis were identified and no device-related complications were reported for any of the patients. Collectively, this study shows that the MasSpec Pen system can be successfully incorporated into the operating room, allowing direct detection of rich molecular profiles from tissues with a seconds-long turnaround time that could be inform surgical and clinical decisions without disrupting tissue analysis workflows.

On the issue of tangential necrectomy in burn surgery (literature review)

Relevance. Treatment of choice for patients with deep burns is early surgery, i.e. necrectomy with simultaneous plastic closure of the postoperative defect. However, technical implementation of necrectomy is still under debate.Intention. To assess current scientific views on the use of tangential necrectomy in the surgical treatment of burn victims.Methodology. A literature survey was carried out using PubMed database, the Google Academy search engine, and also resources of the Scientific electronic library (eLIBRARY.ru).Results and Discussion. The analysis allows us to conclude that at present tangential necrectomy for burn injuries is not generally approved. There is no convincing data on its indications, acceptable areas of simultaneously excised tissues and ex cision depth are not determined, the technique for performing tangential necrectomy using an electrodermatome has not been developed. There is no information on effective methods for closing postoperative defects using tangential excision of a scab.Conclusion. Thus, tangential necrectomy indications as well as acceptable areas of simultaneously dissected tissues and the depth of excision, tangential necrectomy technique via electrodermatome for closing postoperative wound defects need evidence-based justification.

Multi-modal Nonlinear Optical and Thermal Imaging Platform for Label-Free Characterization of Biological Tissue

The ability to characterize the combined structural, functional, and thermal properties of biophysically dynamic samples is needed to address critical questions related to tissue structure, physiological dynamics, and disease progression. Towards this, we have developed an imaging platform that enables multiple nonlinear imaging modalities to be combined with thermal imaging on a common sample. Here we demonstrate label-free multimodal imaging of live cells, excised tissues, and live rodent brain models. While potential applications of this technology are wide-ranging, we expect it to be especially useful in addressing biomedical research questions aimed at the biomolecular and biophysical properties of tissue and their physiology.