Does a common pathophysiological basis exist in the association of ulcerative colitis and Takayasu's aortitis? Report of a case.

A case of a young Japanese woman with long-standing ulcerative colitis complicated by preinfarction angina due to Takayasu's aortitis is presented. Successful emergency aorto-coronary bypass operation was performed. Whether the association of these two diseases can be explained by a common mechanism is discussed.     

Flat adenoma and flat mucosal carcinoma (IIb type)— A new precursor of colorectal carcinoma?

Two flat adenomas and a flat mucosal carcinoma of the colon were reported in patients with synchronous and metachronous colonic carcinomas. These lesions were almost flat and were not detected by preoperative endoscopic examinations. Colonoscopists should be aware of the presence of flat adenomas, which can be easily missed, and recognize them as lesions that play an important role in the "adenoma-carcinoma sequence."     

Growth and Production of Steroid Saponin in Solanum aculeatissimum During One Vegetation Period

SOLANUM ACULEATISSIMUM (Solanaceae) plants, which were cultivated in the open field, were harvested once a month from June 1985 to January 1986. The growth matter and content of steroid saponins, aculeatiside A and B which are precursors of steroid hormones in root, were then measured in order to examine their seasonal variations during one vegetation period. The aerial parts of the plants died of chill and frost in January. In November the dry weight of root reached the maximum, and the content of steroid saponins was more than 10% and showed a maximum. The yield of steroid saponins per plant was greatest in November. These results suggest that November is the appropriate time for harvest, and that S. ACULEATISSIMUM can be more useful than the DIOSCOREA species which is now used as a source plant of steroid hormones.     

Increased levels of serum tissue inhibitor of metalloproteinase-1 but not metalloproteinase-3 in atopic dermatitis

Matrix metalloproteinases and their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs), contribute to inflammation-induced tissue destruction and subsequent remodeling for maintenance of tissue homeostasis. Since the production of these enzymes and their inhibitors is regulated by mediators such as proinflammatory cytokines and growth factors, elevated levels of serum TIMPs and/or MMPs have been documented in patients with several inflammatory disorders. In this study, we examined the role of TIMPs and MMPs in the pathogenesis of atopic dermatitis (AD) by evaluating the serum levels of TIMP-1 and MMP-3 in 40 patients with AD and 20 control subjects by ELISA. The serum TIMP-1 levels were significantly higher in AD patients in exacerbation status than in nonatopic subjects, whereas serum MMP-3 levels were not significantly different between them. As a result, AD patients revealed significantly elevated TIMP-1/MMP-3 ratios. The levels of serum TIMP-1 were significantly reduced in AD patients following conventional treatments. Significantly higher values of peripheral eosinophil counts, serum levels of IgE and lactate dehydrogenase, eruption score, and eruption area were noted in the AD patients with elevated TIMP-1 levels when compared with those with normal values. Moreover, the points of chronic eruptions such as lichenification and prurigo were significantly higher in the patients with elevated TIMP-1 levels than those with normal TIMP-1, while those of acute lesions such as oozy/microvesicles and oedema were not different between these groups. Serum TIMP-1 level may be a useful marker to estimate the long-term disease activity of AD.     

Usefulness of Intraprocedural Pulmonary Venous Flow for Predicting Recurrent Mitral Regurgitation and Clinical Outcomes After Percutaneous Mitral Valve Repair With the MitraClip

Objectives

The aim of this study was to determine the prognostic value of pulmonary venous (PV) flow during MitraClip implantation.

Prediction of human pharmacokinetics for low‐clearance compounds using pharmacokinetic data from chimeric mice with humanized livers

Development of low‐clearance (CL) compounds that are slowly metabolized is a major goal in the pharmaceutical industry. However, the pursuit of low intrinsic CL (CL_int) often leads to significant challenges in evaluating the pharmacokinetics of such compounds. Although in vitro–in vivo extrapolation is widely used to predict human CL, its application has been limited for low‐CL_int compounds because of the low turnover of parent compounds in metabolic stability assays. To address this issue, we focused on chimeric mice with humanized livers (PXB‐mice), which have been increasingly reported to accurately predict human CL in recent years. The predictive accuracy for nine low‐CL_int compounds with no significant turnover in a human hepatocyte assay was investigated using PXB‐mouse methods, such as single‐species allometric scaling (PXB‐SSS) approach and a novel physiologically based scaling (PXB‐PBS) approach that assumes that the CL_int per hepatocyte is equal between humans and PXB‐mice. The percentages of compounds with predicted CL within 2‐ and 3‐fold ranges of the observed CL for low‐CL_int compounds were 89% and 100%, respectively, for both PXB‐SSS and PXB‐PBS approaches. Moreover, the predicted CL was mostly consistent among the methods. Conversely, the percentages of compounds with predicted CL within 2‐ and 3‐fold ranges of the observed CL for low‐CL_int compounds were 50% and 63%, respectively, for multispecies allometric (MA) scaling. Overall, these PXB‐mouse methods were much more accurate than conventional MA scaling approaches, suggesting that PXB‐mice are useful tools for predicting the human CL of low‐CL_int compounds that are slowly metabolized.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

It is important to identify low‐clearance (CL) compounds that are slowly metabolized during the drug discovery process, but the ability of in vitro–in vivo extrapolation to predict human CL decreases as the value of intrinsic CL (CL_int) decreases. Although chimeric mice with humanized livers (PXB‐mice) have been reported to be useful for predicting human CL, their applicability to low‐CL_int compounds with no significant turnover in human hepatocyte assays has not been clarified.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study examined the predictive accuracy of PXB‐mouse methods for low‐CL_int compounds.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

In addition to the previously reported single‐species allometric scaling approach, we proposed a novel physiologically based scaling approach. Both methods displayed much greater predictive accuracy for low‐CL_int compounds than conventional multispecies allometric scaling approaches.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

The findings should improve the accuracy of human pharmacokinetic prediction and enable efficient and safe first‐in‐human studies.     

Diffusion tensor imaging in chronic subdural hematoma: correlation between clinical signs and fractional anisotropy in the pyramidal tract

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) was introduced as a good technique to evaluate structural abnormalities in the white matter. In this study, we used DTI to examine anisotropic changes of the pyramidal tracts displaced by chronic subdural hematoma (CSDH).MATERIALS AND METHODS: Twenty-six patients with unilateral CSDH underwent DTI before and after surgery. We measured fractional anisotropy (FA) values in pyramidal tracts of bilateral cerebral peduncles and calculated the ratio of the FA value on the lesion side to that on the contralateral side (FA ratio) and compared the ratios with motor weakness. Moreover, the relationships between FA ratios and clinical factors such as age, sex, midline shift, interval from trauma, and hematoma attenuation on CT were evaluated.RESULTS: FA values of pyramidal tracts on the lesion side were significantly lower than those on the contralateral side (0.66 ± 0.07 versus 0.74 ± 0.05, P < .0001). The FA ratio was correlated to the severity of motor weakness (r² = 0.32, P = .002). FA ratios after surgery improved significantly compared with those before surgery (0.96 ± 0.08 versus 0.89 ± 0.07, P = .0004). Intervals from trauma and the midline shift were significantly associated with decreased FA ratios (P = .0008 and P = .037).CONCLUSIONS: In patients with CSDH, a reversible decrease of FA in the affected pyramidal tract on DTI was correlated to motor weakness. These anisotropic changes were considered to be caused by a reversible distortion of neuron fibers and vasogenic edema due to the hematoma.

Chronic subdural hematoma (CSDH) is a progressive space-occupying lesion, which may lead to reversible reduction in cerebral function due to brain compression or brain displacement. The causes, clinical characteristics, and therapeutic management of CSDH are well established; however, the detailed physiology, including the mechanisms of appearance with motor dysfunction in patients, is still controversial.^1–4Diffusion tensor imaging (DTI) reveals the tissue microstructure and architecture of white matter tracts, including pyramidal tracts, and extracts the principal diffusivities, mean diffusivities (MD), and fractional anisotropy (FA). Previously, it was reported that decreased FA in the pyramidal tracts on DTI was associated with secondary degeneration and could be a reliable measure of motor weakness.^5–8 The purpose of this study was to investigate changes of DTI in affected pyramidal tracts of patients with CSDH and to evaluate the association between changes of FA and clinical factors such as age, sex, hematoma thickness, midline shift, interval from the trauma, and attenuation on CT.