Quantitative whole body biodistribution of fluorescent-labeled agents by non-invasive tomographic imaging

When small molecules or proteins are injected into live animals, their physical and chemical properties will significantly affect pharmacokinetics, tissue penetration, and the ultimate routes of metabolism and clearance. Fluorescence molecular tomography (FMT) offers the ability to non-invasively image and quantify temporal changes in fluorescence throughout the major organ systems of living animals, in a manner analogous to traditional approaches with radiolabeled agents. This approach is best used with biotherapeutics (therapeutic antibodies, or other large proteins) or large-scaffold drug-delivery vectors, that are minimally affected by low-level fluorophore conjugation. Application to small molecule drugs should take into account the significant impact of fluorophore labeling on size and physicochemical properties, however, the presents studies show that this technique is readily applied to small molecule agents developed for far-red (FR) or near infrared (NIR) imaging. Quantification by non-invasive FMT correlated well with both fluorescence from tissue homogenates as well as with planar (2D) fluorescence reflectance imaging of excised intact organs (r2 = 0.996 and 0.969, respectively). Dynamic FMT imaging (multiple times from 0 to 24 h) performed in live mice after the injection of four different FR/NIR-labeled agents, including immunoglobulin, 20-50 nm nanoparticles, a large vascular imaging agent, and a small molecule integrin antagonist, showed clear differences in the percentage of injected dose per gram of tissue (%ID/g) in liver, kidney, and bladder signal. Nanoparticles and IgG1 favored liver over kidney signal, the small molecule integrin-binding agent favored rapid kidney and bladder clearance, and the vascular agent, showed both liver and kidney clearance. Further assessment of the volume of distribution of these agents by fluorescent volume added information regarding their biodistribution and highlighted the relatively poor extravasation into tissue by IgG1. These studies demonstrate the ability of quantitative FMT imaging of FR/NIR agents to non-invasively visualize and quantify the biodistribution of different agents over time.     

The use of thermal imaging in assessing skin temperature following cryotherapy: a review

Background

Cryotherapy is used in various clinical and sporting settings to reduce odema, decrease nerve conduction velocity, decrease tissue metabolism and to facilitate recovery after exercise induced muscle damage. The basic premise of cryotherapy is to cool tissue temperature and various modalities of cryotherapy such as whole body cryotherapy, cold spray, cryotherapy cuffs, frozen peas, cold water immersion, ice, and cold packs are currently being used to achieve this. However, despite its widespread use, little is known regarding the effectiveness of different cryotherapy modalities to reduce skin temperature.

Objectives

To provide a synopsis of the use of thermal imaging as a method of assessing skin temperature following cryotherapy and to report the magnitude of skin temperature reductions associated with various modalities of cooling.

Design

Structured narrative review.

Methods

Three electronic databases were searched using keywords and MESH headings related to the use of thermal imaging in the assessment of skin temperature following cryotherapy. A hand-search of reference lists and relevant journals and text books complemented the electronic search.

Summary

Nineteen studies met the inclusion criteria. A skin temperature reduction of 5–15 °C, in accordance with the recent PRICE (Protection, Rest, Ice, Compression and Elevation) guidelines, were achieved using cold air, ice massage, crushed ice, cryotherapy cuffs, ice pack, and cold water immersion. There is evidence supporting the use and effectiveness of thermal imaging in order to access skin temperature following the application of cryotherapy.

Conclusions

Thermal imaging is a safe and non-invasive method of collecting skin temperature. Although further research is required, in terms of structuring specific guidelines and protocols, thermal imaging appears to be an accurate and reliable method of collecting skin temperature data following cryotherapy. Currently there is ambiguity regarding the optimal skin temperature reductions in a medical or sporting setting. However, this review highlights the ability of several different modalities of cryotherapy to reduce skin temperature.     

Effect of whole body cryotherapy on the levels of some hormones in professional soccer players

INTRODUCTION: The study was undertaken to determine blood serum concentrations of selected steroid hormones (estradiol--E(2), testosterone--T, dehydroepiandrosterone sulfate--DHEA-S) and luteinizing hormone (LH) in professional footballers subjected to whole body cryotherapy. MATERIAL AND METHODS: Twenty-two clinically healthy males, mean age 26.7 years, were studied. The subjects underwent ten sessions of whole body cryotherapy in Wroclaw-type chamber, with kinesitherapy following each session. Blood samples were collected before and two days after the treatment and the results were analyzed statistically. RESULTS: After the treatment there was a significant decrease in the concentrations of T (6.01 vs. 4.80 ng/mL, p < 0.01) and E(2) (102.3 vs. 47.5 pg/mL, p < 0.00001), but no DHEA-S and LH. The T/E(2) ratio showed a significant increase form 72.2 to 136.5 (p < 0.01). CONCLUSIONS: Whole body cryotherapy leads to a significant decrease in serum T and E(2), with no effect on LH and DHEAS levels. As a results of cryotherapy, the T/E(2) ratio was significant increased. The changes observed are probably due to cryotherapy-induced alternation in the blood supply to the skin and subcutaneous tissue, as well as to modulation of the activity of aromatase which is responsible for conversion of testosterone and androstenedione to estrogens.     

Human whole body imaging and detection of breast tumours by n.m.r

A brief review of recent developments in line scan imaging of large objects is given, together with some representative images showing anatomical detail and a discussion of some spin-lattice relaxation time mapping results. Current progress in high speed imaging by means of the echo planar technique is reported and some preliminary results obtained at both 15.0 and 4.0 MHz are discussed.     

Probing whole cell currents in high-frequency electrical fields: identification of thermal effects

An open-end coaxial probe is combined with a planar patch-clamp system to apply electric fields with GHz frequencies during conventional patch-clamp measurements. The combination of pulsed microwave irradiation and lock-in detection allows for the separation of fast and slow effects and hence facilitates the identification of thermal effects. The setup and the influence of radiation on the patch-clamp current are thoroughly characterized. For the independent optical verification of heating effects, a temperature microscopy technique is applied with high spatial, temporal and temperature resolution. It is shown that the effect of radiation at GHz frequencies on whole cell currents is predominantly thermal in nature in the case of RBL cells with an endogenous K(ir) 2.1 channel.     

Early biological effects of whole body irradiation on rat lungs

Summary The influence of whole-body irradiation (WBI) with 4, 8 and 15 Gyionizing radiation upon some biochemical indices in the brochoalveolar lavage fluid (BALF) of rat lungs was studied. It was established that lactate dehydrogenase (LDH), alkaline phosphatase, (APH) and acid phosphatase (AcPH) activities show a dose-dependent decrease on the day 1 and day 5 after the irradiation. A similar trend was observed in the total protein content on the day 1. Angiotensin converting enzyme (ACE) activity was increased on the day 1 in the groups irradiated with 8 Gy and 15 Gy in comparison with the controls (190,2% and 187,5%, respectively). It was concluded that WBI decreass LDH, APH and AcPH levels in the lung cells, which secrete them into bronchoalveolar spaces. An irradiation with 8 Gy and 15 Gy WBI provokes an early damage on cytoplasmic membranes of the endothelial cells in lung capillars. It was considered that the bronchoalveolar lavage can find a more wide application for evaluation of the biological effect of ionizing radiation in lungs.     

Normalizing the thermal effects of radiofrequency radiation: body mass versus total body surface area

The current guideline for exposure to radiofrequency radiation (RFR) was developed through assessment of the biological effects data collected primarily from the rat. The consensus that a lack of hazardous biological effects occurred below a whole-body-averaged specific absorption rate (SAR) of 4.0 W/kg led to the proposition of a 0.4 W/kg guideline with a built-in safety factor of 10. This paper demonstrates that if the RFR absorption rate in the rat had been normalized with respect to total body surface area rather than body mass, the exposure guideline would be 2.3 W/m2, which translates to an SAR of approximately 0.06 W/kg for an adult human. It is further shown that a given RFR absorption rate, normalized as a fraction of a species' heat loss per unit of surface area, is independent of body mass over a range of 0.03-100 kg; however, a normalization of the RFR absorption rate to heat loss per unit of body mass is highly dependent on the species' mass. Normalizing the rate of RFR absorption to the surface area of the rat indicates that the current RFR exposure guideline of 0.4 W/kg may be too high.     

Regulation of immune activity by mild (fever-range) whole body hyperthermia: effects on epidermal Langerhans cells

Inflammation of the skin and systemic fever, both of which occur with injury or infection, include a hyperthermic component that many believe constitutes a physiological stress. Such increases in local or systemic body temperature may also have a regulatory effect on immune function. Langerhans cells (LCs), the dendritic cells of the skin, continuously monitor the extracellular matrix of the skin by taking up particles and microbes that they then carry to draining lymph nodes for presentation to T lymphocytes. We hypothesize that the thermal element of inflammation and/or fever may help regulate the activation and migration of LCs out of the epidermis. To test this hypothesis, Balb/ c mice were exposed to a mild (39.8 degrees C +/- 0.2 degrees C), long-duration (6 hours) whole body hyperthermia (WBH) treatment, which mimics the thermal component of fever. The number of LCs and their morphology were analyzed at various time points up to 7 days after the initiation of WBH. The LCs of the ear epidermis were visualized using a fluorescein isothiocyanate-conjugated antibody specific for the major histocompatibility complex (MHC) class II molecule and confocal microscopy. Although MHC class II staining was diffuse on the surface of the LC body and dendritic extensions of both WBH and control samples, the WBH-treated LCs exhibited a more punctate morphology with fewer dendritic processes compared with control LCs. A significant decrease in the number of LCs was also observed 1 to 5 days after WBH treatment. Furthermore, in vitro heating of Balb/c ear skin cultures at 40 degrees C for 6 to 8 hours enhanced the numbers of viable LCs that migrated into the culture wells. These results suggest that WBH treatment stimulates epidermal LCs in the absence of foreign antigen.     

全脊柱MR成像9例失败原因分析

目的:探讨全脊柱MR成像中因体位设计、参数设置、病人配合等因素造成全眷柱MR成像失败的原因及其解决方法.方法:采用GE SIGNA双梯度HDx 1.5-T磁共振成像系统,专用8通道全脊柱相控阵线圈,GE AW4.3图像后处理工作站,拼接处理软件pasting 1.1.利用自动移床技术一次定位分两段扫描,即颈胸段和胸腰骶段;将矢状位、冠状位扫描图像传至后处理工作站,通过pasting 1.1软件将上下两段同一序列图像分别进行自动的无缝隙拼接生成全脊柱图像.结果:79例中全脊柱MR成像失败9例;其中4例因体位设计不当或在两序列扫描间歇期由于患者左右移动,使得脊髓正中面不能拼接在一幅图像中;有3例因上下两段的层数、扫描起始位置不一致或扫描定位时定位线偏转了一定角度,使得全脊柱图像序列中有几幅只有上段或只有下段原始扫描图像;有1例因下段扫描野过小使得全脊柱图像序列中胸12椎体层面信息缺失;还有1例因扫描下段T2W1像时患者向上移动了一段距离,使得全脊柱图像T2WI序列中颈1-腰5只有22个椎体显示.其余70例均获得准确、直观的全椎管内脊髓及椎体结构的影像.结论:要获得高质量的全脊柱MR成像,必须选择正确的扫描参数,体位设计时要求操作者有足够的细心和耐心一次性摆好体位,还要和患者有良好的沟通以便取得患者最好的配合.     

Radioprotection by whole body hyperthermia: possible mechanism(s)

Studies were carried out to gain an insight into the mechanisms underlying WBH induced radioprotection. The plasma levels of IL-1α, IL-6, TNF-α and GM-CSF, were elevated in WBH treated mice between 2 and 6 h after treatment. The total nucleated cell count of hemopoietic tissues such as spleen, thymus, bone marrow and peripheral blood showed drastic reduction without recovery until death in mice treated with TBI. However, the nucleated cell count in the above tissues showed significant recovery after initial drop in WBH and WBH+TBI treated groups and reached to a normal level by day 7 and day 28, respectively. The total WBC and RBC count in peripheral blood recovered to a control level by day 28 after treatment. Significant number of endogenous spleen colonies were detected, 14 days after TBI in WBH pre-treated mice whereas no such spleen colonies could be detected in TBI treated group. The transplantation of bone marrow derived from control, WBH, TBI and WBH+TBI treated groups of mice to lethally irradiated mice (8 Gy) showed formation of spleen colonies only in mice which received bone marrow from control, WBH and WBH+TBI treated groups. Transplantation of the bone marrow from these groups of mice resulted in prolonged survival of lethally irradiated mice as compared to mice receiving bone marrow from TBI treated mice. These results seem to suggest that WBH induced radioprotection of mice could be due to immunomodulation manifested through induction of cytokines responsible for protection and proliferative response, leading to accelerated recovery from hemopoietic damage-a major cause of radiation induced death.     

Lower strontium in two different body matrices in neurodevelopmental disorders: A preliminary report

BackgroundEnvironmental factors, including elemental homeostasis, have not been studied sufficiently in neurodevelopmental disorders (NDD). This study aims to compare the status of 13 elements in blood and deciduous teeth dentine of children having an autism spectrum disorder or attention deficit hyperactivity disorder with typically developing controls.MethodsElements including calcium, phosphorus, magnesium, iron, zinc, copper, chromium, manganese, mercury, lead, cadmium, molybdenum, and strontium in both deciduous teeth and blood were analyzed by inductively coupled plasma mass spectrometry.ResultsStrontium levels in both blood and teeth samples were found to be significantly lower in the NDD group. Additionally, blood cadmium and mercury levels, and copper/zinc ratio were higher in the NDD group.ConclusionsOur results warrant further investigation in a large series of NDD examining symptom levels and genetic variations associated with elemental homeostasis.     

Pressure changes induced by whole body acceleration shocks

In the present paper pressure changes induced by sudden body acceleration are studied "in vivo" on the dog and compared to the results obtainable with a recently developed mathematical model. A dog was fixed to a movable table, which was accelerated by a compressed air piston for less than 1 s. Acceleration was varied by changing the air pressure in the piston. Pressure was measured during the experiment at different points along the vascular bed. However, only data obtained in the carotid artery and abdominal aorta are presented here. The results demonstrated that impulse body accelerations cause significant pressure peaks in the vessel examined (about + 25 mmHg in the carotid artery with body acceleration of g/2). Moreover, pressure changes are rapidly damped, with a time constant of about 0.1s. From the present results it may be concluded that, according to the prediction of the mathematical model, body accelerations such as those occurring in normal life can induce pressure changes well beyond the normal pressure value.     

A preliminary biomechanical study of cyclic preconditioning effects on canine cadaveric whole femurs

Biomechanical preconditioning of biological specimens by cyclic loading is routinely done presumably to stabilize properties prior to the main phase of a study. However, no prior studies have actually measured these effects for whole bone of any kind. The aim of this study, therefore, was to quantify these effects for whole bones. Fourteen matched pairs of fresh-frozen intact cadaveric canine femurs were sinusoidally loaded in 4-point bending from 50?N to 300?N at 1?Hz for 25 cycles. All femurs were tested in both anteroposterior (AP) and mediolateral (ML) bending planes. Bending stiffness (i.e., slope of the force-vs-displacement curve) and linearity R(2) (i.e., coefficient of determination) of each loading cycle were measured and compared statistically to determine the effect of limb side, cycle number, and bending plane. Stiffnesses rose from 809.7 to 867.7?N/mm (AP, left), 847.3 to 915.6?N/mm (AP, right), 829.2 to 892.5?N/mm (AP, combined), 538.7 to 580.4?N/mm (ML, left), 568.9 to 613.8?N/mm (ML, right), and 553.8 to 597.1?N/mm (ML, combined). Linearity R(2) rose from 0.96 to 0.99 (AP, left), 0.97 to 0.99 (AP, right), 0.96 to 0.99 (AP, combined), 0.95 to 0.98 (ML, left), 0.94 to 0.98 (ML, right), and 0.95 to 0.98 (ML, combined). Stiffness and linearity R(2) versus cycle number were well-described by exponential curves whose values leveled off, respectively, starting at 12 and 5 cycles. For stiffness, there were no statistical differences for left versus right femurs (p?=?0.166), but there were effects due to cycle number (p?相似文献   

The effects of hyperbaric oxygen treatment on vigility of spermatozoids: preliminary report

The aim of this study was to evaluate the effect of hyperbaric oxygen treatment (HBO) to the vigilance of spermatozoids. The sperm samples were obtained from the patients (n=10) with diagnosed oligospermia. The motility of spermatozoids in tested samples was not lower than 30% but it did not exceed the critical proportion of 50%. Three groups of samples were formed, with respectively 10 samples in each group. All of them were exposed to HBO conditions of 2.5 ATA for 90 minutes. Group I was exposed to HBO conditions without any addition of medium. Group II was added 5 ml of EBSS solution. Tyrode's solution in volume of 5 ml was added to group III. The evaluation of functional characteristics of sperm was carried out 30 minutes after completion of HBO treatment. Statistically significant increased in motor activity was registered in three all groups (p<0.05). The biggest increased in vigilance of spermatozoids was found in the samples of the group III (p<0.01), exceeding the critical proportion of 50% in all of the samples. The obtained results suggest that the acute exposure of the sperm samples to HBO has favorable impact to functional capacity of spermatozoids in view of their better motility.