The three layered structure of orbicularis oris and buccinator complex with partial connection at the modiolus and partial direct continuation.

PURPOSE: This study aimed to clarify the structural arrangement of the orbicularis oris (OOr), the buccinator, and the other perioral muscles around the modiolus. METHODS: The perioral muscles in seventeen cadavers fixed with formalin were dissected in situ and/or in isolated muscle specimens, and their layers were reconstructed schematically upon pantomographic view of the skeleton to evaluate their actions. RESULTS: The buccinator was composed of three parts including upper and lower oblique parts in its superficial layer and a middle transverse part in its deep layer. The superior and inferior OOr were composed of an inner marginal part (IM) and an outer labial part (OL) in each. The perioral muscles as a whole were arranged in three layers. The first layer consisted of the depressor anguli oris and the OL of superior OOr connected at the modiolus in a vertical direction. The second layer consisted of the upper and inner oblique part of buccinator and a part of the OL of inferior OOr connected at the modiolus in a horizontal direction. The third layer contained the middle transverse part of buccinator continuous with the IM of both OOr and a part of the OL of inferior OOr without connection to the modiolus. CONCLUSIONS: The different arrangement of the three layers of perioral muscles around the modiolus could serve as a good basis to predict the actions of the individual perioral muscles on the movement of lips in open/close of the oral fissure and widening/narrowing of the lip width.

Unique morphological architecture of the hamstring muscles and its functional relevance revealed by analysis of isolated muscle specimens and quantification of structural parameters.

The structural and functional differences of individual hamstrings have not been sufficiently evaluated. This study aimed to clarify the morphological architecture of the hamstrings including the superficial tendons in detail using isolated muscle specimens, together with quantification of structural parameters of the muscle. Sixteen lower limbs of human cadavers were used in this study. The semimembranosus (SM), semitendinosus (ST), biceps femoris long head (BFlh), and biceps femoris short head (BFsh) were dissected from cadavers to prepare isolated muscle specimens. Structural parameters, including muscle volume, muscle length, fiber length, sarcomere length, pennation angle, and physiological cross-sectional area (PCSA) were measured. In addition, the proximal and distal attachment areas of the muscle fibers were measured, and the proximal/distal area ratio was calculated. The SM, ST, and BFlh were spindle-shaped with the superficial origin and insertion tendons on the muscle surface, and the BFsh was quadrate with direct attachment to the skeleton and BFlh tendon. The muscle architecture was pennate in the four muscles. The four hamstrings possessed either of two types of structural parameters, one with shorter fiber length and larger PCSA, as in the SM and BFlh, and the other with longer fiber length and smaller PCSA, as in the ST and BFsh. Sarcomere length was unique in each of the four hamstrings, and thus the fiber length was suitably normalized using the average sarcomere length for each, instead of uniform length of 2.7 µm. The proximal/distal area ratio was even in the SM, large in the ST, and small in the BFsh and BFlh. This study clarified that the superficial origin and insertion tendons are critical determinants of the unique internal structure and structural parameters representing the functional properties of the hamstring muscles.

Pharmacokinetics and Safety of Single and Multiple Doses of Peficitinib (ASP015K) in Healthy Chinese Subjects.

Objective: To investigate the pharmacokinetics and safety of peficitinib (Janus kinase inhibitor for the treatment of rheumatoid arthritis) in healthy Chinese subjects following single and multiple doses. Methods: This open-label, randomized study was conducted at one site in China. Subjects received peficitinib 50, 100 or 150 mg as a single dose on Day 1 (fasted) and once daily from Days 8 to 13 in the multiple-dose period (fed). Blood samples were collected before administration each day, and up to 72h post administration. Pharmacokinetic assessments included area under the concentration curve (AUC), half-life (t1/2), maximum concentration (Cmax), and time to maximum concentration (tmax) of peficitinib and its metabolites (H1, H2 and H4). Treatment-emergent adverse events (TEAEs) were evaluated. Results: Thirty-six subjects were enrolled (12 per dose group). After a single dose of peficitinib, median tmax was 1.0-1.5h and mean t1/2 was 7.4-13.0h for all doses. In the multiple-dose period, median tmax was 1.5-2.0h. Dose-proportional increases in Cmax and AUC24h were observed for peficitinib and its metabolites following single and multiple doses, with minimal drug accumulation. The major metabolite was H2, with a systemic exposure of >150% of the parent AUC. Drug-related TEAEs were experienced by 5 (13.9%) and 12 (33.3%) subjects in the single- and multiple-dose periods, respectively. Following multiple doses of peficitinib, TEAEs were more frequent in higher than lower dose groups but were mild in severity with no related discontinuation or death. Conclusion: Following single and multiple doses of peficitinib in healthy Chinese subjects, peficitinib demonstrated rapid absorption and was well tolerated at all doses. Clinicaltrialsgov Identifier: NCT04143477.

Intralobular distribution of ovarian-like stroma in pancreatic mucinous cystic neoplasms: a discussion on its tumorigenesis.

Pancreatic mucinous cystic neoplasm (MCN) has two histological components: tumor epithelia and ovarian-like stroma (OLS). To examine the progression and changes in pancreatic MCNs, we analyzed the distribution, amount, immunohistochemical phenotype, presence of theca cells of OLS, and tumor epithelium in 45 surgically resected MCN cases, comparing them with tumor sizes. The OLS data of female MCN cases were also compared between those who were ≤ 51 years old and those > 51 years old to see the effect of menopause on MCN histology. Non-mucinous type epithelium was present in all low-grade MCNs, but its ratio decreased with tumor size (p < 0.001), suggesting that epithelial mucinous changes are a progression phenomenon. The intralobular distribution of OLS was observed in 28.8% of MCN cases and was related to smaller tumor size (p < 0.0001), suggesting intralobular involvement of early MCNs. The nuclear expression of ß-catenin and the cytoplasmic expression of α-smooth muscle actin (SMA) was observed in almost all OLS. OLS tended to be lesser among female cases aged > 51 years than those ≤ 51 years old, however it did not reach statistical significance. This is the first study to show the intralobular distribution of OLS.

Effect of Roxadustat on the Pharmacokinetics of Simvastatin, Rosuvastatin, and Atorvastatin in Healthy Subjects: Results From 3 Phase 1, Open-Label, 1-Sequence, Crossover Studies.

Roxadustat inhibits breast cancer resistance protein and organic anion transporting polypeptide 1B1, which can affect coadministered statin concentrations. Three open-label, 1-sequence crossover phase 1 studies in healthy subjects were conducted to assess effects from steady-state 200-mg roxadustat on pharmacokinetics and tolerability of 40-mg simvastatin (CL-0537 and CL-0541), 40-mg atorvastatin (CL-0538), or 10-mg rosuvastatin (CL-0537). Statins were dosed concomitantly with roxadustat in 28 (CL-0537) and 24 (CL-0538) healthy subjects, resulting in increases of maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve from the time of dosing extrapolated to infinity (AUCinf ) 1.87- and 1.75-fold for simvastatin, 2.76- and 1.85-fold for simvastatin acid, 4.47- and 2.93-fold for rosuvastatin, and 1.34- and 1.96-fold for atorvastatin, respectively. Additionally, simvastatin dosed 2 hours before, and 4 and 10 hours after roxadustat in 28 (CL-0541) healthy subjects, resulted in increases of Cmax and AUCinf 2.32- to 3.10-fold and 1.56- to 1.74-fold for simvastatin and 2.34- to 5.98-fold and 1.89- to 3.42-fold for simvastatin acid, respectively. These increases were not attenuated by time-separated statin dosing. No clinically relevant differences were observed for terminal elimination half-life. Concomitant 200-mg roxadustat and a statin was generally well tolerated during the study period. Roxadustat effects on statin Cmax and AUCinf were statin and administration time dependent. When coadministered with roxadustat, statin-associated adverse reactions and the need for statin dose reduction should be evaluated.

Potential differences in chitin synthesis ability cause different sensitivities to diflubenzuron among three strains of Daphnia magna.

Ecotoxicity testing of crustaceans using Daphnia magna has been implemented in the chemical management systems of various countries. While the chemical sensitivity of D. magna varies depending on genetically different clonal lineages, the strain used in ecotoxicity tests, including the acute immobilization test (OECD TG202), has not been specified. We hypothesized that comprehensive gene expression profiles could provide useful information on phenotypic differences among strains, including chemical sensitivity. To test this hypothesis, we performed mRNA sequencing on three different strains (NIES, England, and Clone 5) of D. magna under culture conditions. The resulting expression profile of the NIES strain was clearly different compared to the profiles of the other two strains. Gene ontology (GO) enrichment analysis suggested that chitin metabolism was significantly enriched in the NIES strain compared to that in the England strain. Consistent with the GO analysis, evidence of high levels of chitin metabolism in the NIES strain were observed across multiple levels of biological organization, such as expression of chitin synthase genes, chitin content, and chitinase activity, which suggested that the different strains would exhibit different sensitivities to chemicals used to inhibit chitin synthesis. We found that among all strains, the NIES strain was more tolerant to diflubenzuron, a chitin synthesis inhibitor, with a 14-fold difference in the 48 h-EC50 value for the acute immobilization test compared to the England strain. The present study demonstrates that the differences among strains in chitin metabolism may lead to sensitivity difference to diflubenzuron, and serves as a case study of the usefulness of comprehensive gene expression profiles in finding sensitivity differences.

Anatomic characterization of the tibial and fibular nutrient arteries in humans.

The location of nutrient foramina has been extensively studied in long bones; however, accurate information on the origin and extra-osseous course of the nutrient artery remains clearly defined in some long bones, although it is crucial to protect the nutrient arteries during operative procedures. In this study, we elucidated the origin and extra-osseous course of tibial and fibular nutrient arteries based on the 54 cadaveric legs. The tibial nutrient artery typically arose from the posterior tibial artery. Some of the tibial nutrient arteries arose from the anterior tibial, popliteal, and fibular arteries. The tibial nutrient artery arose from these parent arteries as a long descending branch. It penetrated the most proximal portion of the tibialis posterior or flexor digitorum longus to enter the tibial nutrient foramen. The fibular nutrient artery arose from the fibular artery as a short descending branch in all the cases. The fibular nutrient artery penetrated the flexor hallucis longus to enter the fibular nutrient foramen. Our present and previous findings provide new insight into the anatomical characteristics for the nutrient arteries in the long bones of upper and lower extremities. Namely, the nutrient arteries of the long bones go away from the elbow or knee to enter the nutrient foramina.

Anatomical study of the soleus: Application to improved imaging diagnoses.

INTRODUCTION: Strains of the soleus are widely found both in amateur and professional athletes. For their accurate regional diagnoses, understanding the anatomy of the spatial relationship between muscular fibers and tendinous structures is important because their interfaces are susceptible sites to muscle strains. Therefore, this study evaluated the precise architecture of the soleus. MATERIALS AND METHODS: We evaluated the precise anatomical architecture of the soleus in 87 formaldehyde-fixed soleus muscles. To calculate mean relative physiological cross-sectional area of each muscular fiber compartment, we measured the fiber length, volume, and pennation angle in isolated compartments. RESULTS: The posterior soleus surface was covered by a broad aponeurotic posterior insertion tendon (PIT), which continued inferiorly to the insertion tendon. The anterior surface had three aponeurotic origin tendons, lateral origin tendon (LOT), medial origin tendon (MOT), and tendinous arch, which were arranged along the soleus margins. The anterior bipennate muscle portion (ABP), surrounded by the three origin structures, terminated as the sagittal insertion tendon (SIT), which continued inferiorly to PIT. The posterior main muscle portion behind LOT and MOT was separated into lateral and medial portions by the SIT. The soleus thus possessed a broad musculotendinous junction. Furthermore, ABP exhibited wide structural diversity in shape and size: in extreme cases, it was duplicated or absent. CONCLUSION: Systematic anatomical descriptions of the soleus will be useful for accurate regional diagnosis of its strains with magnetic resonance imaging and ultrasonography.

Pancreaticoduodenectomy with reconstructing blood flow of the gastric conduit after esophagectomy with concomitant celiac axis stenosis: a case report.

BACKGROUND: Pancreaticoduodenectomy after esophageal resection is technically difficult, because blood flow of the gastric conduit should be preserved. Celiac axis stenosis (CAS) is also a problem for pancreaticoduodenectomy, because arterial blood supply for the liver comes mainly through the collateral route from the superior mesenteric artery (SMA) via the gastroduodenal artery (GDA). Herein, we report the case of a patient with pancreatic head cancer who underwent a pancreaticoduodenectomy after esophagectomy with concomitant CAS. CASE PRESENTATION: A 76-year-old man with pancreatic head cancer was referred to our department. He had a history of esophagectomy with retrosternal gastric conduit reconstruction for esophageal cancer. Computed tomography showed severe CAS and a dilated collateral route between the SMA and the splenic artery (SPA). We prepared several surgical options depending on the intraoperative findings, and performed radical pancreaticoduodenectomy with concomitant resection of the distal gastric conduit. The right gastroepiploic artery (RGEA) of the remnant gastric conduit was fed from the left middle colic artery (MCA) with microvascular anastomosis. Despite CAS, when the GDA was dissected and clamped, good blood flow was confirmed, and the proper hepatic artery did not require reconstruction. The patient was discharged on postoperative day 90. CONCLUSIONS: We successfully performed radical pancreaticoduodenectomy after esophagectomy with concomitant CAS, having prepared multiple surgical options depending upon the intraoperative findings.

Manipulation of phase slips in carbon-nanotube-templated niobium-nitride superconducting nanowires under microwave radiation.

We study the manipulation of thermal/quantum phase slips (tPSs/qPSs) in ultra-thin niobium-nitride superconducting nanowires (scNW) grown on carbon-nanotube templates. These NWs exhibit resistive steps in current-voltage (I-V) characteristics, and the number of phase slip centers (PSCs) in an NW can be tuned by the NW length. Under microwave (MW) radiation, emergence of each single PSC can be precisely controlled by varying the MW power. For thin and short scNW, a dip structure between the qPS-dominated low-temperature region and the tPS-dominated high-temperature region were observed owing to anti-proximity effect by electrodes.

The influence of trunk muscle strength on walking velocity in elderly people with sarcopenia.

[Purpose] Sarcopenia increases the risk of falls and fractures. However, its relationship with walking, which is the generation mechanism of falls, has not been clarified. The purpose of this study was to clarify the trunk muscle strength and the characteristics of walking, in elderly people with sarcopenia. [Participants and Methods] The participants were 40 elderly people aged 65 years and over. The participants were able to walk without assistance and were attending outpatient rehabilitation or community day-care centers. The assessment and measurement items included: the presence or absence of sarcopenia (using the diagnostic criteria of the Asian Working Group for Sarcopenia), lower limb and trunk muscle strength, and characteristics of walking. The participants were divided into two groups depending on the presence or absence of sarcopenia, and a comparison was made between the two groups. [Results] The participants in the sarcopenia group had significantly lower trunk extension muscle strength as compared to the participants in the non-sarcopenia group. In addition, the hip joint maximum flexion moment, ankle joint maximum plantar flexion moment, and walking velocity of participants in the sarcopenia group were significantly lower than those in the non-sarcopenia group. [Conclusion] This study revealed that weakness of the trunk muscle strength causes a decrease in walking velocity in elderly people with sarcopenia.

Clinical and Prognostic Values of ALBI Score in Patients With Acute Heart Failure.

BACKGROUND: Although liver dysfunction is one of the common complications in patients with acute heart failure (AHF), no integrated marker has been defined. The albumin-bilirubin (ALBI) score has recently been proposed as a novel, clinically-applicable scoring system for liver dysfunction. We investigated the utility of the ALBI score in patients with AHF compared to that for a preexisting liver dysfunction score, the Model of End-Stage Liver Disease Excluding prothrombin time (MELD XI) score. METHODS: We evaluated ALBI and MELD XI scores in 1,190 AHF patients enrolled in the prospective, multicentre Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure study. The associations between the two scores and the clinical profile and prognostic predictive ability for 1-year mortality were evaluated. RESULTS: The mean MELD XI and ALBI scores were 13.4±4.8 and -2.25±0.48, respectively. A higher ALBI score, but not higher MELD XI score, was associated with findings of fluid overload. After adjusting for pre-existing prognostic factors, the ALBI score (HR 2.11, 95% CI: 1.60-2.79, p<0.001), but not the MELD XI score (HR 1.02, 95% CI: 0.99-1.06, p=0.242), was associated with 1-year mortality. Likewise, area under the receiver-operator-characteristic curves for 1-year mortality significantly increased when the ALBI score (0.71 vs. 0.74, p=0.020), but not the MELD XI score (0.71 vs. 0.72, p=0.448), was added to the pre-existing risk factors. CONCLUSIONS: The ALBI score is potentially a suitable liver dysfunction marker that incorporates information on fluid overload and prognosis in patients with AHF. These results provide new insights into heart-liver interactions in AHF patients.

Relationship between the Induced Iron Overload Model and Hepatic Erythropoiesis in Xenopus laevis.

Iron is an essential element for hemoglobin synthesis during erythropoiesis. Iron overload, in contrast, adversely affects erythropoiesis and causes organ dysfunction. Research using various animal models may help to elucidate pathophysiological mechanisms induced by excess iron. In the present study, we evaluated the relationship between iron metabolism and erythropoietic activity in the African clawed frog, Xenopus laevis. In X. laevis, both erythropoiesis and iron metabolism occur in the liver. First, we developed a method to quantify iron levels in the liver and plasma using 2-nitroso-5-[N-n-propyl-N-(3-sulfopropyl) amino] phenol (Nitroso-PSAP). We then measured iron levels and analyzed hematopoietic parameters in frogs that were orally administered sodium ferrous citrate (SFC). The hepatic iron level increased in the SFC group, but the number of erythrocytes, hematocrit, and hemoglobin concentration did not change, suggesting that the regulation of the production and release of mature erythrocytes in the liver was not directly affected by dietary iron. At four days after administration of 2 mg/kg SFC, the number of immature erythrocytes decreased in the liver. Interestingly, atypical blood cells with hyper-segmented nuclei were observed, identified by acridine orange cell staining; these atypical blood cells were hardly detectable under the steady state. Compared with previously reported results in mice, the increase in the hepatic iron levels was small, but our results indicate that SFC affects hematopoietic activity. These results establish a novel model for iron metabolism and provide new insights into the relationship between iron metabolism and erythropoiesis in vertebrates.

Anatomic characterization of the femoral nutrient artery: Application to fracture and surgery of the femur.

The localization of nutrient foramina and direction of nutrient canals have been studied. However, information about the origin and extraosseous course of nutrient arteries is lacking in some types of long tubular and irregular bones. Thus, we aimed to reexamine the origin and course of the femoral nutrient artery (FNA) through cadaveric dissection to clarify its anatomic characteristics. Sixty thighs were collected from 57 cadavers. To fix the cadavers and visualize the small arterial branches, 10% formalin was injected from the femoral artery, followed by an injection of acrylic ink. The arterial tree in the posterior part of the thigh was recorded by line drawings. The femur received single or double FNAs via the femoral nutrient foramina, which were on and along the linea aspera. In cases with single FNA (41 of the 60 thighs), it typically arose from the four parts of the profunda femoris system: profunda femoris artery between the origins of the third and fourth perforating arteries; second perforating artery; third perforating artery; and terminal branch. In cases with double FNAs (remaining 19 thighs), the superior FNA typically arose from the second perforating artery, and the inferior FNA arose from the terminal branch of the profunda femoris artery and popliteal system. FNAs are described as branches of the perforating arteries in Terminologia Anatomica and anatomy textbooks. However, we found that FNAs also frequently arose from the profunda femoris artery and popliteal system, in addition to the perforating arteries. Clin. Anat. 33:479-487, 2020. © 2019 Wiley Periodicals, Inc.

An Open-Label, Single-Dose, Human Mass Balance Study of Amenamevir in Healthy Male Adults.

Amenamevir is an inhibitor of the helicase-primase enzyme complex developed for the treatment of varicella zoster virus. This mass balance study investigated the absorption, metabolism, and excretion of a single dose (200 mg) of 14 C-labeled amenamevir in healthy male volunteers. Blood, urine, and feces samples were collected for up to 8 days after the dose. Safety and tolerability were assessed through voluntary reporting of adverse events, physical examination, and clinical laboratory testing. Amenamevir was rapidly absorbed, with a median time to peak drug concentration of 1.0 to 1.5 hours and a plasma half-life of 8 to 9 hours. Overall, 95.3% of the administered dose was recovered, with the majority of radiolabeled drug excreted in feces (74.6%) followed by urine (20.6%). The major route of elimination was fecal, with around 70% of the dose excreted as metabolites and <0.1% as the unchanged drug. Metabolic profiling revealed that predominantly radiolabeled amenamevir (80%) and its hydroxyl metabolite R5 (up to 7.1%) were present in plasma. Single-dose amenamevir was well tolerated; 3 transient and mild adverse events were reported in 3 subjects. Overall, >95% of a single 200-mg dose of amenamevir was eliminated by 168 hours after the dose, with the major route of elimination being fecal.

Specialty-Related Differences in the Acute-Phase Treatment and Prognosis in Patients With Acute Heart Failure　- Insights From REALITY-AHF.

BACKGROUND: The aim of this study was to assess specialty-related differences in the treatment for patients with acute heart failure (AHF) in the acute phase and subsequent prognostic differences. Methods and Results: We analyzed hospitalizations for AHF in REALITY-AHF, a multicenter prospective registry focused on very early presentation and treatment in patients with AHF. All patients were classified according to the medical specialty of the physicians responsible for contributed most to decisions regarding the initial diagnosis and treatment after the emergency department (ED) arrival. Patients initially managed by emergency physicians (n=614) or cardiologists (n=911) were analyzed. After propensity-score matching, vasodilators were used less often by emergency physicians than by cardiologists at 90 min after ED arrival (29.8% vs. 46.1%, P<0.001); this difference was also observed at 6, 24, and 48 h. Cardiologists administered furosemide earlier than emergency physicians (67 vs. 102 min, P<0.001). However, the use of inotropes, noninvasive ventilation, and endotracheal intubation were similar between groups. In-hospital mortality did not differ between patients managed by emergency physicians and those managed by cardiologists (4.1% vs. 3.8%, odds ratio 1.12; 95% confidence interval 0.58-2.14). CONCLUSIONS: Despite differences in initial management, no prognostic difference was observed between emergency physicians and cardiologists who performed the initial management of patients with AHF.

A phase I, open-label, single-dose micro tracer mass balance study of 14C-labeled ASP7991 in healthy Japanese male subjects using accelerator mass spectrometry.

ASP7991 is a calcimimetic that acts on the calcium-sensing receptor on parathyroid cell membranes and suppresses parathyroid hormone (PTH) secretion in the treatment of secondary hyperparathyroidism. The mass balance and metabolite profile of [14C]ASP7991 were investigated in six healthy male subjects after a single oral dose of [14C]ASP7991 [1 mg, 18.5 kBq (500 nCi)] in solution. [14C] radioactivity in plasma, urine and feces was analyzed using Accelerator mass spectrometry. ASP7991 was rapidly absorbed, metabolized and excreted. Mean recovery of [14C] radioactivity in urine and feces was 30.08% and 49.31%, respectively, and mean total recovery of [14C] radioactivity was 79.39%. The majority of [14C] radioactivity in urine and feces was excreted within the first 72 h following administration. Seven metabolites were detected in plasma, urine and feces samples, and their structures were determined by mass spectrometry. The main metabolic pathways of ASP7991 in humans were predicted to be N-dealkylation, followed by N-acetylation and taurine conjugation to a carboxylic acid moiety. Our findings show that a mass balance study using micro radioactivity doses is suitable for elucidating the pharmacokinetics of the absorption, metabolism and excretion of administered drugs.

Reevaluation of the superior radial collateral artery in the human upper arm.

The superior radial collateral artery (SRCA) was described in well-established anatomy textbooks published in the 1800s. According to those textbooks, the SRCA originates from the brachial artery, passes transversely between the coracobrachialis and the humerus, and distributes to the most distal portion of the deltoid. The SRCA is not listed in the international standard on anatomical terminology, Terminologia Anatomica, or in modern anatomy textbooks. In the present study, we reevaluated the anatomical features of the SRCA by cadaveric dissection. We found that two kinds of SRCAs were consistently present in the upper arm. One was similar to the previous descriptions of the SRCA in terms of origin and course, but the distribution was somewhat different. The other was similar to the previous descriptions in terms of the distribution, although it differed in origin and course. The discrepancy between the description of the SRCA in classical textbooks and the actual morphologies of the SRCA presumably prompted previous anatomists to question the existence of the SRCA, resulting in its absence from anatomical textbooks after a particular time point.

Anatomic characterization of the radial and ulnar nutrient arteries in humans.

BACKGROUND: The localization of nutrient foramens has been extensively studied in humans and other vertebrate animals. However, accurate information on the origin and extraosseous course of the nutrient arteries in some types of long tubular bones is lacking. Terminologia Anatomica, the international standard on human anatomic terminology, lists the radial nutrient artery (RNA) and the ulnar nutrient artery (UNA) as branches of the radial and ulnar arteries, respectively. Anatomy textbooks published in both German- and English-speaking countries regard both the RNA and UNA as branches of the anterior interosseous artery. METHODS: To clarify the anatomic characteristics of the RNA and UNA in humans, we reexamined the origin and course of these arteries by cadaveric dissection. RESULTS: Almost all RNAs and UNAs branched from the ulnar artery or its tributaries. In typical cases, the RNA branched from the anterior interosseous artery and the UNA branched from the proximal part of the ulnar artery or the anterior interosseous artery. These findings are reasonable from the perspective of regional anatomy, since the ulnar artery passes more deeply than the radial artery in the proximal forearm and thus the proximal part of the ulnar artery and its major branches are situated more closely to the radial and ulnar nutrient foramens. CONCLUSIONS: Based on our findings, it is necessary to correct the position of the RNA and UNA in the arterial hierarchy of T. Anatomica for accurate morphological description.

Two Phase 1, Open-Label, Mass Balance Studies to Determine the Pharmacokinetics of 14 C-Labeled Isavuconazonium Sulfate in Healthy Male Volunteers.

Isavuconazonium sulfate is the water-soluble prodrug of the active triazole isavuconazole. Two phase 1 studies were conducted to identify the metabolic profile and mass balance of isavuconazole and BAL8728 (inactive cleavage product). Seven subjects in study 1 (isavuconazole mass balance) received a single oral dose of [cyano-14 C]isavuconazonium sulfate corresponding to 200 mg isavuconazole. Six subjects in study 2 (BAL8728 mass balance) received a single intravenous dose of [pyridinylmethyl-14 C]isavuconazonium sulfate corresponding to 75 mg BAL8728. Pharmacokinetic parameters of radioactivity in whole blood and plasma and of isavuconazole and BAL8728 in plasma were assessed. Radioactivity ratio of blood/plasma, percentage of dose, and cumulative percentage of radioactive dose recovered in urine and feces for isavuconazole and BAL8728 were assessed. Metabolic profiling was carried out by high-performance liquid chromatography and mass spectrometry. Mean plasma isavuconazole pharmacokinetic parameters included apparent clearance (2.3 ± 0.7 L/h), apparent volume of distribution (301.8 ± 105.7 L), and terminal elimination half-life (99.9 ± 44.6 hours). In study 1, isavuconazole-derived radioactivity was recovered approximately equally in urine and feces (46.1% and 45.5%, respectively). In study 2, BAL8728-derived radioactivity was predominantly recovered in urine (96.0%). Isavuconazole (study 1) and M4 (cleavage metabolite of BAL8728; study 2) were the predominant circulating components of radioactivity in plasma.