Preliminary Clinical Testing Research Articles

Rapid tear screening of diabetic retinopathy by a detachable surface acoustic wave enabled immunosensor

BackgroundDiabetic retinopathy (DR), a chronic and progressive microvascular complication of diabetes mellitus, substantially threatens vision and is a leading cause of blindness among working-age individuals worldwide. Traditional diagnostic methods, such as ophthalmoscopy and fluorescein angiography are nonquantitative, invasive, and time consuming. Analysis of protein biomarkers in tear fluid offers noninvasive insights into ocular and systemic health, aiding in early DR detection. This study introduces a surface acoustic wave (SAW) microchip that rapidly enhances fluorescence in bead-based immunoassays for the sensitive and noninvasive DR detection from human tear samples. ResultsThe device facilitated particle mixing for immunoassay formation and particle concentration in the droplet, resulting in an enhanced immunofluorescence signal. This detachable SAW microchip allows the disposal of the cover glass after every use, thereby improving the reusability of the interdigital transducer and minimizing potential cross-contamination. A preliminary clinical test was conducted on a cohort of 10 volunteers, including DR patients and healthy individuals. The results demonstrated strong agreement with ELISA studies, validating the high accuracy rate of the SAW microchip. SignificanceThis comprehensive study offers significant insights into the potential application of a novel SAW microchip for the early detection of DR in individuals with diabetes. By utilizing protein biomarkers found in tear fluid, the device facilitates noninvasive, rapid, and sensitive detection, potentially revolutionizing DR diagnostics and improving patient outcomes through timely intervention and management of this vision-threatening condition.

A Wireless and Wearable Body-Pressure-Monitoring System for the Prevention of Pressure-Induced Skin Injuries.

This article presents a wireless and wearable body-pressure-monitoring system for the on-site, real-time prevention of pressure injuries for immobilized patients. For the prevention of pressure-induced skin injuries, a wearable pressure sensor system is designed to monitor the pressure at multiple sites on the skin and to alert the danger of prolonged application of pressure on the skin with a pressure-time integral (PTI) algorithm. The wearable sensor unit is developed using a pressure sensor based on a liquid metal microchannel and integrated with a flexible printed circuit board that includes a thermistor-type temperature sensor. The wearable sensor unit array is connected to the readout system board for the transmission of measured signals to a mobile device or PC via Bluetooth communication. We evaluate the pressure-sensing performances of the sensor unit and the feasibility of the wireless and wearable body-pressure-monitoring system through an indoor test and a preliminary clinical test at the hospital. It is shown that the presented pressure sensor has high-quality performance with excellent sensitivity to detect both high and low pressure. The proposed system measures the pressure at bony sites on the skin for about six hours continuously without any disconnection or failure, and the PTI-based alarming system operates successfully in the clinical setup. The system measures the pressure applied to the patient and provides meaningful information from the measured data for early diagnosis and prevention of bedsores to doctors, nurses, and healthcare workers.

Fabrication of three-dimensional orthodontic force detecting brackets and preliminary clinical test for tooth movement simulation

This study aimed to develop an ultraminiature pressure sensor array to measure the force exerted on teeth. Orthodontic force plays an important role in effective, rapid, and safe tooth movement. However, owing to the lack of an adequate tool to measure the orthodontic force in vivo, it remains challenging to determine the best orthodontic loading in clinical and basic research. In this study, a three-dimensional (3D) orthodontic force detection system based on piezoresistive absolute pressure sensors was designed. The 3D force sensing array was constructed using five pressure sensors on a single chip. The size of the sensor array was only 4.1 × 2.6 mm, which can be placed within the bracket base area. Based on the barometric calibration, conversion formulas for the output voltage and pressure of the five channels were constructed. Subsequently, a 3D linear mechanical simulation model of the voltage and stress distribution was established using 312 tests of the applied force in 13 operating modes. Finally, the output voltage was first converted to pressure and then to the resultant force. The 3D force-detection chip was then tested to verify the accuracy of force measurement on the teeth. Based on the test results, the average output force error was only 0.0025 N (0.7169%) (p = 0.958), and the average spatial positioning error was only 0.058 mm (p = 0.872) on the X-axis and 0.050 mm (p = 0.837) on the Y-axis. The simulation results were highly consistent with the actual force applied (intraclass correlation efficient (ICC): 0.997–1.000; p < 0.001). Furthermore, through in vivo measurements and a finite element analysis, the movement trends generated when the measured orthodontic forces that acted on the teeth were simulated. The results revealed that the device can accurately measure the orthodontic force, representing the first clinical test of an orthodontic-force monitoring system. Our study provides a hardware basis for clinical research on efficient, safe, and optimal orthodontic forces, and has considerable potential for application in monitoring the biomechanics of tooth movement.

Preliminary clinical testing to inform development of the Critical Care Pain Observation Tool for Families (CPOT-Fam)

ABSTRACT Introduction Many patients in the intensive care unit (ICU) cannot communicate. For these patients, family caregivers (family members/close friends) could assist in pain assessment. We previously adapted the Critical Care Pain Observation Tool (CPOT) for family caregiver use (CPOT-Fam). In this study, we conducted preliminary clinical evaluation of the CPOT-Fam to inform further tool development. Methods For preliminary testing, we collected (1) pain assessments of patients in the ICU from family caregivers (CPOT-Fam) and nurses (CPOT) and determined the degree of agreement (kappa coefficient, κ) and (2) collected openended feedback on the CPOT-Fam from family caregivers. For refinement, we used preliminary testing data to refine the CPOT-Fam with a multidisciplinary working group. Results We assessed agreement between family caregiver and nurse pain scores for 29 patients. Binary agreement (κ) between CPOT-Fam and CPOT item scores (scores ≥2 considered indicative of significant pain) was fair, κ = 0.43 (95% confidence interval [CI] 0.18–0.69). Agreement was highest for the CPOT-Fam items ventilator compliance/vocalization (weighted κ = 0.48, 95% CI 0.15–0.80) and lowest for muscle tension (weighted κ = 0.10, 95% [CI] −0.17 to 0.20). Most participants (n = 19; 69.0%) reported a very positive experience using the CPOT-Fam, describing it as “good” and “easy-to-use/clear/straightforward.” We iteratively refined the CPOT-Fam over five cycles using the data collected until no further revisions were suggested. Conclusion Our preliminary clinical testing suggests that family involvement in pain assessment in the ICU is well perceived. The CPOT-Fam has been further refined and is now ready for clinical pilot testing to determine its feasibility and acceptability.

Electronic Nose Development and Preliminary Human Breath Testing for Rapid, Non-Invasive COVID-19 Detection.

We adapted an existing, spaceflight-proven, robust "electronic nose" (E-Nose) that uses an array of electrical resistivity-based nanosensors mimicking aspects of mammalian olfaction to conduct on-site, rapid screening for COVID-19 infection by measuring the pattern of sensor responses to volatile organic compounds (VOCs) in exhaled human breath. We built and tested multiple copies of a hand-held prototype E-Nose sensor system, composed of 64 chemically sensitive nanomaterial sensing elements tailored to COVID-19 VOC detection; data acquisition electronics; a smart tablet with software (App) for sensor control, data acquisition and display; and a sampling fixture to capture exhaled breath samples and deliver them to the sensor array inside the E-Nose. The sensing elements detect the combination of VOCs typical in breath at parts-per-billion (ppb) levels, with repeatability of 0.02% and reproducibility of 1.2%; the measurement electronics in the E-Nose provide measurement accuracy and signal-to-noise ratios comparable to benchtop instrumentation. Preliminary clinical testing at Stanford Medicine with 63 participants, their COVID-19-positive or COVID-19-negative status determined by concomitant RT-PCR, discriminated between these two categories of human breath with a 79% correct identification rate using "leave-one-out" training-and-analysis methods. Analyzing the E-Nose response in conjunction with body temperature and other non-invasive symptom screening using advanced machine learning methods, with a much larger database of responses from a wider swath of the population, is expected to provide more accurate on-the-spot answers. Additional clinical testing, design refinement, and a mass manufacturing approach are the main steps toward deploying this technology to rapidly screen for active infection in clinics and hospitals, public and commercial venues, or at home.

Design of a Multi-Sensor System for Exploring the Relation between Finger Spasticity and Voluntary Movement in Patients with Stroke.

A novel wearable multi-sensor data glove system is developed to explore the relation between finger spasticity and voluntary movement in patients with stroke. Many stroke patients suffer from finger spasticity, which is detrimental to their manual dexterity. Diagnosing and assessing the degrees of spasticity require neurological testing performed by trained professionals to estimate finger spasticity scores via the modified Ashworth scale (MAS). The proposed system offers an objective, quantitative solution to assess the finger spasticity of patients with stroke and complements the manual neurological test. In this work, the hardware and software components of this system are described. By requiring patients to perform five designated tasks, biomechanical measurements including linear and angular speed, acceleration, and pressure at every finger joint and upper limb are recorded, making up more than 1000 features for each task. We conducted a preliminary clinical test with 14 subjects using this system. Statistical analysis is performed on the acquired measurements to identify a small subset of features that are most likely to discriminate a healthy patient from patients suffering from finger spasticity. This encouraging result validates the feasibility of this proposed system to quantitatively and objectively assess finger spasticity.

Preliminary Clinical Validation Results of a Deep Learning Approach for Ankle Brachial Index Prediction in Noncompressible Tibial Vessels

The ankle brachial index (ABI) is limited by its inability to derive accurate values for noncompressible tibial vessels owing to falsely elevated readings. We have presented the preliminary clinical testing results of a deep learning approach to predict the ABI ranges directly from Doppler sounds for patients with noncompressible tibial vessels with high accuracy and the goal of alleviating the current limitations in ABI measurements.

Acute Toxicity Evaluation of a new Benzimidazole derivative on the wistar rat

3-[2-(1H-Benzimidazol-2-ylsulfanyl)-ethyl]-1,3-oxazolidin-2-one (OXB1) is a new Benzimidazole derivative which was synthesized in our laboratory then characterized with several physicochemical techniques. However, its related toxic effect remains unknown. The present work aims to study its acute toxicity in normal Wistar rats. Six groups of rats received an intrapéritonéale (i.p.) injection of different doses of OXB1 (500, 700, 900, 1000 and 1200mg/kg) and were daily monitored for 14 days. Mortalities, changes in food and water uptake, behavioral changes and weight were monitored. The OXB1 Lethal Dose 50 (LD50) was 1084mg/kg. The administration of the studied molecule at a dose of 900mg/kg did not affect animal viability and body weight (bw). In addition, food and water intake are unchanged. Furthermore, at the this dose, the levels of hematological and biochemical values and organ’s weights were not affected which confirm that the No-Observed-Adverse-Effect Level (NOAEL) dose of OXB1 is 900 mg/kg in normal Wistar rats and could possibly be tested after further analysis in a preliminary clinical test.

Endocannabinoid signaling in glioma.

High-grade gliomas constitute the most frequent and aggressive form of primary brain cancer in adults. These tumors express cannabinoid CB1 and CB2 receptors, as well as other elements of the endocannabinoid system. Accruing preclinical evidence supports that pharmacological activation of cannabinoid receptors located on glioma cells exerts overt anti-tumoral effects by modulating key intracellular signaling pathways. The mechanism of this cannabinoid receptor-evoked anti-tumoral activity in experimental models of glioma is intricate and may involve an inhibition not only of cancer cell survival/proliferation, but also of invasiveness, angiogenesis, and the stem cell-like properties of cancer cells, thereby affecting the complex tumor microenvironment. However, the precise biological role of the endocannabinoid system in the generation and progression of glioma seems very context-dependent and remains largely unknown. Increasing our basic knowledge on how (endo)cannabinoids act on glioma cells could help to optimize experimental cannabinoid-based anti-tumoral therapies, as well as the preliminary clinical testing that is currently underway.

Novel Three-Dimensional Knitted Fabric for Pressure Ulcer Prevention: Preliminary Clinical Application and Testing in a Diabetic Mouse Model of Pressure Ulcers.

Background Population aging has led to an increased incidence of pressure ulcers, resulting in a social burden and economic costs. We developed a three-dimensional knitted fabric (3-DKF) with a pressure-reducing function that can be applied topically in the early stages of pressure ulcers to prevent progression. Methods We evaluated the effects of the 3-DKF in a streptozotocin-induced diabetes mellitus pressure ulcer mouse model, and the fabric was preliminarily applied to patients. Twelve-week-old male C57BL/6 mice were used for the animal experiments. In the pressure ulcer mouse model, an ischemia-reperfusion injury was created using a magnet on the dorsa of the mice. Pressure was measured with BodiTrak before and after applying the 3-DKF to 14 patients at risk of sacral pressure ulcers. Results In the 3-DKF-applied mice group, the ulcers were shallower and smaller than those in the control group. Compared with the mice in the control group, the 3-DKF group had lower platelet-derived growth factor-α and neutrophil elastase expression, as parameters related to inflammation, and increased levels of transforming growth factor (TGF)-β1, TGF-β3, proliferating cell nuclear antigen, and α-smooth muscle actin, which are related to growth factors and proliferation. Additionally, typical normal tissue staining patterns were observed in the 3-DKF group. In the preliminary clinical analysis, the average skin pressure was 26.2 mm Hg before applying the 3-DKF, but it decreased to an average of 23.4 mm Hg after 3-DKF application. Conclusion This study demonstrated that the newly developed 3-DKF was effective in preventing pressure ulcers through testing in a pressure ulcer animal model and preliminary clinical application.

Design and Evaluation of pH-Dependent Nanosystems Based on Cellulose Acetate Phthalate, Nanoparticles Loaded with Chlorhexidine for Periodontal Treatment.

This work aimed to develop and evaluate pH-dependent systems based on nanospheres (NSphs) and nanocapsules (NCs) loaded with chlorhexidine (CHX) base as a novel formulation for the treatment of periodontal disease. Cellulose acetate phthalate (CAP) was employed as a pH-dependent polymeric material. The NSphs and NCs were prepared using the emulsion-diffusion technique and then characterized according to encapsulation efficiency (EE), size, zeta-potential, morphology, thermal properties, release profiles and a preliminary clinical panel test. The formulations showed 77% and 61% EE and 57% and 84% process efficiency (PE), respectively. Both systems were spherical with an average size of 250–300 nm. Differential scanning calorimetry (DSC) studies showed that the drug has the potential to be dispersed molecularly in the NSph matrix or dissolved in the oily center of the NCs. The CHX release test revealed that the release of NSphs-CHX follows Fickian diffusion involving diffusion-erosion processes. The NCs showed a slower release than the NSphs, following non-Fickian diffusion, which is indicative of anomalous transport. These nanosystems may, therefore, be employed as novel formulations for treating periodontal disease, due to (1) their coverage of a large surface area, (2) the controlled release of active substances at different pH, and (3) potential gingival tissue infiltration.

Abdominal radiograph preliminary clinical evaluation image test bank project

IntroductionLiterature documenting preliminary clinical evaluation (PCE) commonly focuses on the evaluation of musculoskeletal radiographs. Despite this, the professional body suggest that a diagnostic radiographer should be able to provide a PCE for any radiograph. MethodsAn image bank of 30 abdominal radiographs was designed comprising of 17 abnormal cases with a range of pathologies which one could expect to encounter in the emergency department (ED). Participants' were asked to select one of four taxonomies to represent their PCE for each radiograph. Participants' answers were compared to a gold standard PCE taxonomy based on the radiological report. Inferential statistics were applied to assess for any significant different in accuracy between NHS pay bands of the participants. ResultsOn average participants selected an abdominal radiograph PCE taxonomy with a sensitivity of 75.2% and a specificity of 75.7%. Whilst band 7 radiographers selected the most accurate abdominal radiograph PCE and had the highest area under curve (AUC), no significant difference was found in the PCE categorisation of abdominal radiographs by radiographers of all pay bands. ConclusionParticipants' have shown good sensitivity in recognising prominent findings on abdominal radiographs. This sensitivity is however reduced when assessing less obvious radiographic appearances, illustrating areas where additional training would be beneficial. The study provides evidence towards the consideration of an expansion of current practice regarding the implementation of a scheme of abdominal radiograph PCE. Further research with a larger cohort of participants' and a lower abnormal case prevalence would be beneficial to the limited research base.

Radiographic capsule-based system for non-cathartic colorectal cancer screening.

Many patients are reluctant to undergo optical colonoscopy for colorectal cancer screening. The Check-Cap colon imaging system is a non-invasive test that comprises an ingestible imaging capsule that emits and detects ultra-low-dose radiation. The capsule generates a 3D reconstruction of the colonic lumen for detection of polyps and cancer. Preliminary preclinical and clinical testing has demonstrated safety and feasibility. Mean radiation dose is estimated at 0.04mSv. In conclusion, we describe a novel capsule-based, patient-friendly colorectal test that holds potential for non-invasive screening.

In vivo acute toxicity assessment of a novel quinoxalinone (6-nitro-2 (1H)-quinoxalinone) in Wistar rats

The quinoxaline derivatives are an important class of heterocyclic compounds, obtained from chemical azote replacement of carbone atom. Fusion of quinoxaline production is relatively easy as they are obviously synthesized by the fusion of two aromatic rings, benzene and pyrazine. The new quinoxalinique derivative, 6-nitro-2 (1H)-quinoxalinone (NQX), has been synthesized in our laboratory. However, the related toxic effect on rat remains unknown. The present work aims to study the acute toxicity of NQX in normal Wistar rats. Seven groups of female rats received an intraperitoneal (i.p.) injection of 0 (control), 20, 40, 60, 120, 200 and 300 mg/kg of the NQX and followed for 14 days. Mortalities, behavioural changes, weight, changes in food and water uptake, urine output and weight of faeces were monitored. At the end of the experiment, the rats receiving the no-observed-adverse-effect level (NOAEL) are sacrificed, blood and organs were collected and haematological and biochemical parameters were analysed in sera sample. The results showed that the NQX Lethal Dose 50 (LD50) was 161.16 mg/kg. The administration of NQX at a dose of 40 mg/kg (NOAEL dose) did not affect animal viability and body weight. In addition, food intake, water intake and urine output remain unchanged. Furthermore, at the NOAEL dose, the levels of blood cells (erythrocytes and leukocytes), haemoglobin, biochemical parameters (glucose, cholesterol, triglycerides, urea, creatinine, bilirubin, total protein and transaminase) and organ’s weights (liver, kidney, spleen, pancreas, heart and brain) were not affected. NQX seems to be relatively saved at the dose of 40 mg/kg in normal Wistar rats and could possibly be tested after further analysis in a preliminary clinical test.

OC24.02: Automated image analysis to estimate gestational age between 18 and 34 weeks using a single 3D brain volume dataset

Ultrasound (US) estimates gestational age (GA) accurately up to ∼24 weeks, but women in low-income settings often present later in pregnancy and with uncertain dates. We hypothesized that GA can be estimated after 24 weeks by analysing the developing fetal brain using an automated algorithm requiring a single 3D US volume dataset. Standardized 3D volumes of the fetal brain were acquired in the axial plane as part of the INTERGROWTH-21st Project. A supervised machine-learning algorithm was developed with data from 18 - 33 + 6 weeks. Random regression forest analyses were applied on a training set of 150 volumes to provide a representation of the brain to ‘learn’ which features were best able to discriminate GA. Testing was performed on a prospectively acquired independent validation sample (n = 150). Model performance was assessed by comparing the modelled (GA: model) with the actual (GA: truth) GA, which was based on the last menstrual period and corroborated by measuring the first trimester crown–rump length. Systematic differences (SD) and 95% limits of agreement (LOA) were evaluated and heat-maps generated to illustrate GA discriminating regions of the brain. The model successfully analysed 138/150 validation volumes to predict GA: model. The SD for GA: model compared to GA:truth was +0.8 days; the 95% LOA were -10.92 to 10.52 days respectively. The thalamus and Sylvian fissure were regions with good GA discriminating features. Obtaining GA estimates using automated analysis of single 3D fetal brain volumes is feasible. Preliminary clinical testing suggests the model is stable. Estimates of model error at 34 weeks are consistent with conventional parameters at ∼22 weeks. Further testing using a range of clinical phenotypes is underway.

SU‐E‐J‐211: Design and Study of In‐House Software Based Respiratory Motion Monitoring, Controlling and Breath‐Hold Device for Gated Radiotherapy

Purpose:The purpose of this present work was to fabricate an in‐house software based respiratory monitoring, controlling and breath‐hold device using computer software programme which guides the patient to have uniform breath hold in response to request during the gated radiotherapy.Methods:The respiratory controlling device consists of a computer, inhouse software, video goggles, a highly sensitive sensor for measurement of distance, mounting systems, a camera, a respiratory signal device, a speaker and a visual indicator. The computer is used to display the respiratory movements of the patient with digital as well as analogue respiration indicators during the respiration cycle, to control, breath‐hold and analyze the respiratory movement using indigenously developed software.Results:Studies were conducted with anthropomophic phantoms by simulating the respiratory motion on phantoms and recording the respective movements using the respiratory monitoring device. The results show good agreement between the simulated and measured movements. Further studies were conducted for 60 cancer patients with several types of cancers in the thoracic region. The respiratory movement cycles for each fraction of radiotherapy treatment were recorded and compared. Alarm indications are provided in the system to indicate when the patient breathing movement exceeds the threshold level. This will help the patient to maintain uniform breath hold during the radiotherapy treatment. Our preliminary clinical test results indicate that our device is highly reliable and able to maintain the uniform respiratory motion and breathe hold during the entire course of gated radiotherapy treatment.Conclusion:An indigenous respiratory monitoring device to guide the patient to have uniform breath hold device was fabricated. The alarm feature and the visual waveform indicator in the system guide the patient to have normal respiration. The signal from the device can be connected to the radiation unit in near future to carry out the gated radiotherapy treatment.

Degradation profile and preliminary clinical testing of a resorbable device for ligation of blood vessels

A resorbable device for ligation of blood vessels was developed and tested in vitro to reveal the degradation profile of the device and to predict the clinical performance in terms of adequate mechanical support during a healing period of 1week. In addition, preliminary clinical testing was performed that showed complete hemostasis and good tissue grip of renal arteries in five pigs. The device was made by injection molding of poly(glycolide-co-trimethylene carbonate) triblock copolymer, and it consisted of a case with a locking mechanism connected to a partly perforated flexible band. A hydrolytic degradation study was carried out for 7, 30 and 60days in water and buffer medium, following the changes in mass, water absorption, pH and mechanical properties. A new rapid matrix-free laser desorption ionization-mass spectrometry (LDI-MS) method was developed for direct screening of degradation products released into the degradation medium. The combination of LDI-MS and electrospray ionization-mass spectrometry analyses enabled the comparison of the degradation product patterns in water and buffer medium. The identified degradation products were rich in trimethylene carbonate units, indicating preferential hydrolysis of amorphous regions where trimethylene units are located. The crystallinity of the material was doubled after 60days of hydrolysis, additionally confirming the preferential hydrolysis of trimethylene carbonate units and the enrichment of glycolide units in the remaining solid matrix. The mechanical performance of the perforated band was followed for the first week of hydrolysis and the results suggest that sufficient strength is retained during the healing time of the blood vessels.

Computational identification and quantification of trabecular microarchitecture classes by 3-D texture analysis-based clustering

High resolution peripheral quantitative computed tomography (HR-pQCT) permits the non-invasive assessment of cortical and trabecular bone density, geometry, and microarchitecture. Although researchers have developed various post-processing algorithms to quantify HR-pQCT image properties, few of these techniques capture image features beyond global structure-based metrics. While 3D-texture analysis is a key approach in computer vision, it has been utilized only infrequently in HR-pQCT research. Motivated by high isotropic spatial resolution and the information density provided by HR-pQCT scans, we have developed and evaluated a post-processing algorithm that quantifies microarchitecture characteristics via texture features in HR-pQCT scans. During a training phase in which clustering was applied to texture features extracted from each voxel of trabecular bone, three distinct clusters, or trabecular microarchitecture classes (TMACs) were identified. These TMACs represent trabecular bone regions with common texture characteristics. The TMACs were then used to automatically segment the voxels of new data into three regions corresponding to the trained cluster features. Regional trabecular bone texture was described by the histogram of relative trabecular bone volume covered by each cluster. We evaluated the intra-scanner and inter-scanner reproducibility by assessing the precision errors (PE), intra class correlation coefficients (ICC) and Dice coefficients (DC) of the method on 14 ultradistal radius samples scanned on two HR-pQCT systems. DC showed good reproducibility in intra-scanner set-up with a mean of 0.870±0.027 (no unit). Even in the inter-scanner set-up the ICC showed high reproducibility, ranging from 0.814 to 0.964. In a preliminary clinical test application, the TMAC histograms appear to be a good indicator, when differentiating between postmenopausal women with (n=18) and without (n=18) prevalent fragility fractures. In conclusion, we could demonstrate that 3D-texture analysis and feature clustering seems to be a promising new HR-pQCT post-processing tool with good reproducibility, even between two different scanners.

Towards the use of cannabinoids as antitumour agents

Various reports have shown that cannabinoids (the active components of marijuana and their derivatives) can reduce tumour growth and progression in animal models of cancer, in addition to their well-known palliative effects on some cancer-associated symptoms. This Opinion article discusses our current understanding of cannabinoids as antitumour agents, focusing on recent insights into the molecular mechanisms of action, including emerging resistance mechanisms and opportunities for combination therapy approaches. Such knowledge is required for the optimization of preclinical cannabinoid-based therapies and for the preliminary clinical testing that is currently underway.

In vitro and in vivo Equivalence Studies of Alendronate Monosodium Tablets

The aim of this study was to test the bioequivalence of two alendronate tablets (CAS 121268-17-5; Marvil 10 and Marvil 70 as test formulations, in short "test"; reference formulation, in short "reference") in vitro and in vivo in healthy adult male subjects and to describe a mode for researching the bisphosphonate oral formulation pharmaceutical quality. Two dissolution tests with 10-mg and 70-mg alendronate tablets, a preliminary clinical test with 10-mg tablets (n = 10) and a bioequivalence study with 70-mg tablets (n = 23) were performed. Clinical studies were single-dose, open, cross-over, randomized, including a four-week wash-out period. Alendronate was assessed by HPLC in urine after 6 (UE6) and 24 (UE24) h post-intake. In all the experiments the reference was the one that had proved efficacy and safety in international regulatory clinical trials. The dissolution test showed a comparable release profile between reference and test, of both, the 10-mg and 70-mg tablet, the difference (f1) and similarity (f2) factors being within the acceptance values. The clinical trials showed great variability in urinary recovery, from one third the average figure up to 2-3 fold. The amount recovered with the 70-mg tablet was 11-15 fold higher than with the 10-mg tablets, suggesting higher (test/reference) was found to be 72-122% for UE24, and when analyzed in individuals with apparent steady bone metabolism during the wash-out period (n = 19), it was 86-137%. Both margins are considered acceptable in view of the particular kinetic and dynamic features of bisphosphonates, their very high inter- and intra-individual variability, extremely low absorption, time-changeable bone compartment, high margin of safety and long-term achievable therapeutic benefits. Test is bioequivalent to reference.