A macroscopic anatomical study of the appropriate palpation zone of the gluteus medius muscle.

[Purpose] Few previous studies have delimitated the palpation zone of the gluteus medius muscle with a focus on its fiber bundles. The purpose of this study was to clarify the morphological characteristics of the gluteus medius muscle using an anatomical approach, and to define its proper palpation zone. [Participants and Methods] In this study, we evaluated thirteen halves of the pelvic region in seven formalin-fixed cadavers.

Prediction of Human Pharmacokinetic Profiles of the Antituberculosis Drug Delamanid from Nonclinical Data: Potential Therapeutic Value against Extrapulmonary Tuberculosis.

Delamanid has been studied extensively and approved for the treatment of pulmonary multidrug-resistant tuberculosis; however, its potential in the treatment of extrapulmonary tuberculosis remains unknown. We previously reported that, in rats, delamanid was broadly distributed to various tissues in addition to the lungs. In this study, we simulated human plasma concentration-time courses (pharmacokinetic profile) of delamanid, which has a unique property of metabolism by albumin, using two different approaches (steady-state concentration of plasma-mean residence time [-MRT] and physiologically based pharmacokinetic [PBPK] modeling).

Feature importance of machine learning prediction models shows structurally active part and important physicochemical features in drug design.

The objective of this study was to obtain the indicators of physicochemical parameters and structurally active sites to design new chemical entities with desirable pharmacokinetic profiles by investigating the process by which machine learning prediction models arrive at their decisions, which are called explainable artificial intelligence. First, we developed the prediction models for metabolic stability, CYP inhibition, and P-gp and BCRP substrate recognition using 265 physicochemical parameters for designing the molecular structures. Four important parameters, including the well-known indicator h_logD, are common in some in vitro studies; as such, these can be used to optimize compounds simultaneously to address multiple pharmacokinetic concerns.

Predicting drug metabolism and pharmacokinetics features of in-house compounds by a hybrid machine-learning model.

We constructed machine learning-based pharmacokinetic prediction models with very high performance. The models were trained on 26138 and 16613 compounds involved in metabolic stability and cytochrome P450 inhibition, respectively. Because the compound features largely differed between the publicly available and in-house compounds, the models learned on the public data could not predict the in-house compounds, suggesting that outside of a certain applicability domain (AD), the prediction results are unreliable and can mislead the design of novel compounds.

Absorption, distribution and excretion of the anti-tuberculosis drug delamanid in rats: Extensive tissue distribution suggests potential therapeutic value for extrapulmonary tuberculosis.

Delamanid (OPC-67683, Deltyba™, nitro-dihydro-imidazooxazoles derivative) is approved for the treatment of adult pulmonary multidrug-resistant tuberculosis. The absorption, distribution and excretion of delamanid-derived radioactivity were investigated after a single oral administration of C-delamanid at 3 mg/kg to rats. In both male and female rats, radioactivity in blood and all tissues reached peak levels by 8 or 24 h post-dose, and thereafter decreased slowly.

Antitubercular Agent Delamanid and Metabolites as Substrates and Inhibitors of ABC and Solute Carrier Transporters.

Delamanid (Deltyba, OPC-67683) is the first approved drug in a novel class of nitro-dihydro-imidazooxazoles developed for the treatment of multidrug-resistant tuberculosis. Patients with tuberculosis require treatment with multiple drugs, several of which have known drug-drug interactions. Transporters regulate drug absorption, distribution, and excretion; therefore, the inhibition of transport by one agent may alter the pharmacokinetics of another, leading to unexpected adverse events.

Anatomical structure of the subcutaneous tissue on the anterior surface of human thigh.

The anterior thighs of 16 limbs from eight donated cadavers were observed using ultrasonic imaging and gross dissection with a specific focus on the subcutaneous tissue, which is considered an auxiliary element of locomotion. On ultrasonic imaging, the subcutaneous tissue was found to comprise multiple layers. The number of layers gradually decreased on progressing distally in the thigh.

Metabolic Mechanism of Delamanid, a New Anti-Tuberculosis Drug, in Human Plasma.

The metabolism of delamanid (OPC-67683, Deltyba), a novel treatment of multidrug-resistant tuberculosis, was investigated in vitro using plasma and purified protein preparations from humans and animals. Delamanid was rapidly degraded by incubation in the plasma of all species tested at 37°C, with half-life values (hours) of 0.64 (human), 0.

Pharmacokinetics and Metabolism of Delamanid, a Novel Anti-Tuberculosis Drug, in Animals and Humans: Importance of Albumin Metabolism In Vivo.

Delamanid, a new anti-tuberculosis drug, is metabolized to M1, a unique metabolite formed by cleavage of the 6-nitro-2,3-dihydroimidazo[2,1-b] oxazole moiety, in plasma albumin in vitro. The metabolic activities in dogs and humans are higher than those in rodents. In this study, we characterized the pharmacokinetics and metabolism of delamanid in animals and humans.

Morphological observation of the horseshoe kidney with circumaortic venous ring.

In a student course of gross anatomy dissection at Knagawa Dental College in 2010, we found an extremely rare case of the horseshoe kidney with circumaortic venous ring in a 43-year-old Japanese male cadaver. In this case, the kidney consisted of three parts: the original kidneys on both sides and an isthmus between them. The location of each kidney was lower than that of the normal kidney.

Expression levels of multidrug resistance-associated protein 4 (MRP4) in human leukemia and lymphoma cell lines, and the inhibitory effects of the MRP-specific inhibitor MK-571 on methotrexate distribution in rats.

In the development of anti-blood cancer drugs, the chronic myelocytic leukemia (KU812), acute myelocytic leukemia (KG-1) and lymphoma (U937) cell lines are commonly used in preclinical pharmacology studies as human cancer xenograft models in mice. In the present study, mRNA expression levels of typical human ATP-binding cassette (ABC) transporters in these human blood cancer cell lines were analyzed by real-time polymerase chain reaction (RT-PCR). Based on the results, the expression level of multidrug resistance-associated protein 4 (MRP4) was found to be extremely high in KU812 cells compared with those of other transporters.

Evaluation of the spinal cord white matter.

Morphological findings or evaluations of the nervous system have traditionally concentrated on cell somata; evaluations of the white matter have not been put forward up to now. This study was conducted to evaluate the white matter in the spinal cord with the LPH discriminative staining method which was proposed by Goto. Thanks to the minimum shrinkage ratio (10 ± 0% in length) which this technique allows, it is possible to evaluate the sizes of nerve axons, and to compare the arrangement of nerve fibers in various parts of the spinal white matter.

Nuclei of the human raphe.

Along the raphe of the brain stem, a series of small neuronal groups can be observed in the medulla oblongata, the pons and the mesencephalon. The neurons located in and adjacent to the raphe are considered to produce mainly serotonin (5-HT). The groups of nuclei containing 5-HT were first reported in experimental animals in the early 1960s.

Decrease in brain distribution of fluvoxamine in experimental hyperlipidemic rats.

Purpose: Many clinical reports and trials have suggested that fluvoxamine (FLV) reduces plasma lipoprotein levels. However, few studies have reported the effect of plasma lipoproteins on FLV pharmacokinetics. The aim of the present study was to investigate the affinities of FLV to plasma lipoproteins and the effect of plasma lipoproteins on the biodistribution of FLV using an experimental hyperlipidemic (HL) rat model.

Double superior vena cava and anomaly of cardiovascular system with a review of the literature.

In a student course of gross anatomy dissection at Kanagawa Dental College in 2008, we found an extremely rare case of the double superior vena cava that has a shunt between the right and left atria of a 81-year-old Japanese male cadaver. The left superior vena cava passed through the space between the left cardiac auricle and the left pulmonary vein and entered the coronary sulcus. Then it opened near the opening of the inferior vena cava as the coronary venous sinus to the right atrium.

Pharmacokinetics of clomipramine, an antidepressant, in poloxamer 407-induced hyperlipidaemic model rats.

Objective: This study was undertaken to investigate the effects of hyperlipidaemia on the pharmacokinetics of clomipramine, an antidepressant, particularly addressing the change of clomipramine distribution to plasma components in poloxamer 407-induced hyperlipidaemia model rats.

Methods: Clomipramine pharmacokinetic studies in hyperlipidaemic rats were performed with clomipramine continuous infusion. Furthermore, clomipramine protein binding and distribution to the brain and plasma components such as lipoproteins were investigated.

Creation of cross-linked electrospun isotypic-elastin fibers controlled cell-differentiation with new cross-linker.

Effective application of elastin materials for vascular grafts in tissue engineering requires these materials to retain the elastic and biological properties of native elastin. To clarify the influence of soluble elastin isotypes on vascular smooth muscle cells (VSMCs), soluble elastin was prepared from insoluble elastin by hydrolysis with oxalic acid. Its fractions were separated and classified into three isotypes.

Morphometric and functional correlation of human neuronal somata: pyramidal motor, special sensory and general sensory systems.

Using an ideal tissue preparation method, we found a definite correlation between various human neuronal somata from the view point of accurate morphometry and functional evaluations. We believe this study may be of value, or even indispensable in the correct understanding of neurological symptomatology and phenomenology.

Effect of serum lipids on the pharmacokinetics of atazanavir in hyperlipidemic rats.

Atazanavir (ATV) has been successfully used in HIV patients with severe hyperlipidemia (HL); however, little is known about the pharmacokinetics of ATV in HL. The aim of this study was to investigate the pharmacokinetics of ATV in HL. With the increase of serum lipids, the protein binding rate in HL rats (approximately 97%) was significantly higher than that in control (approximately 87%).

Morphometric evaluation of the aging process in various human nerve fibers.

We carried out a morphometric comparison of tissue sections from the human spinal cord, medulla oblongata, cranial nerves, autonomic nerves and spinal nerves with the help of a very accurate method that includes two-step fixation, nitrocellulose embedding and discriminative staining. We conducted morphometric evaluations to compare various axonal areas between different individuals using a combination of an image analyzer and a high power microscope. Our study showed a negative correlation between age and axonal area in all nerves except the greater splanchnic nerve.

An anomalous case of the hepatic artery arising from the superior mesenteric artery.

In a stdudenet course of gross anatomy dissection at Kanagawa Dental College in 2006, we found an extremely rare case of the hepatic artery arising from the superior mesenteric artery of a 78-year-old Japanese male cadaver. This case belonged to type V in Adachi's classification of the celiac trunk and the superior mesenteric artery (1928). The gastro-splenic trunk and hepato-mesenteric trunk both arose from the abdominal aorta and the left gastric artery arose from the gastro-splenic trunk.

Morphometric development of the posterior funicular nucleus in the human medulla oblongata.

Using serial sections of 11 human brains of fetuses 18-40 weeks of gestation (WG), 2-month-old infant and 63-year-old adult, we conducted the quantitative analysis of the development of the posterior funicular nucleus (PFN) in the medulla oblongata. The results suggest the following: (1) The cells of the human cuneatus lateralis nucleus are easily distinguished from those of the gracilis nucleus and cuneatus medialis nucleus because the neuronal somatic areas are the largest; the smallest neuronal areas are in the cuneatus medialis nucleus. (2) The development of the PFN occurs at least in four stages characterized by the degree of maturation of the neurons: (a) immature neuronal stage before 20 WG, (b) preparatory stage between (a) and (c), (c) accelerated development stage from 30 to 40 WG, and (d) postnatal stage.

Morphometric comparison of human spinal cord anterior horn cells between the cervical and lumbar levels.

Morphometric comparisons of anterior horn cells (AHCs) were conducted between cervical and lumbar spinal cords in 29 cadavers. The sizes of the AHCs were always larger at the lumbar level than at cervical level irrespective of the age of the spicemens, but a decrease in size with age was observed at both levels. The correlation coefficient shows a larger decrease in numbers and volumes at lumbar level than at cervical level.

Morphological characteristics of nerve cells in the human general sensory system.

We conducted a study to compare morphological characteristics of various nerve cells in the sensory system. This sort of evaluation is indispensable for a better understanding of the nervous system in relation to clinical physiology and neurology.