Investigation of a contributing factor for cervical vertebral stenotic myelopathy using computed tomography for measuring the cervical vertebral volume.

Thoroughbred horses appear to be particularly predisposed to cervical vertebral stenotic myelopathy (CVSM), also known as wobbler syndrome. We hypothesized that variations in the cervical vertebral volumes can affect the dynamic instability of the cervical vertebrae. This observational study aimed to clarify whether cervical vertebral volume could be considered as a contributing factor in CVSM in Thoroughbred horses. Computed tomography (CT) was used to investigate a total of 21 male Thoroughbred horses (age range, 217-1,002 days; mean, 542.3 days). The study population comprised 17 CVSM horses (age range, 217-1,002 days; mean, 549.8 days) and 4 non-CVSM horses (age range, 244-682 days; mean, 510.5 days). The cervical vertebral volumes of three-dimensional CT were measured using the image-processing software. A significant difference in the variation of cervical vertebral volumes among C2 to C4 and C3 to C5 was identified in the CVSM group (P<0.05). While no significant differences were found in the variation in cervical vertebral volumes among C4 to C6. C3 demonstrated a significantly smaller cervical vertebral volume than C2 and C4 (P<0.05). In the non-CVSM group, no significant differences were found in the variation of cervical vertebral volume among C2 to C4, C3 to C5, and C4 to C6. Our findings suggest that variations in cranial cervical vertebral volume in CVSM male horses can be considered as an important contributing factor in CVSM development.

Guillain-Barré syndrome after SARS-CoV-2 infection.

We herein report a case of Guillain-Barré syndrome (GBS) after SARS-CoV-2 infection. The patient was a close contact with a SARS-CoV-2 patient. Initially, she did not have any symptoms and quarantined at a hotel. Dysgeusia and olfactory abnormality appeared at day 6 after testing positive for infection and disappeared by day 9. Subsequently, the patient developed numbness of the arms and legs, difficulty walking, and dyspnea and was referred to our hospital. Her clinical examination showed generalized weakness and hyporeflexia. A cerebrospinal fluid analysis showed albuminocytological dissociation. Her nerve conduction studies were consistent with demyelinating polyneuropathy. Intravenous immunoglobulin was administered based on a diagnosis of GBS.

Optimizing Hemodynamics with Transcatheter Arterial Embolization in Adrenal Pheochromocytoma Rupture.

Pheochromocytoma rupture is rare, and emergent adrenalectomy is associated with a high mortality. We herein report a patient with pheochromocytoma rupture who was stabilized by transcatheter arterial embolization (TAE) and subsequently underwent elective surgery. A 45-year-old man presented with the sudden onset of left lateral abdominal pain, headache, chest discomfort, high blood pressure, and adrenal hemorrhaging on enhanced abdominal computed tomography. TAE was performed under a provisional diagnosis of pheochromocytoma rupture. Following oral doxazosin, he underwent elective left adrenalectomy four and a half months after TAE. Stabilizing the hemodynamic status by TAE before adrenalectomy is a viable option for treating pheochromocytoma rupture.

Ultrasound findings of diffuse metastasis of gastric signet-ring-cell carcinoma to the thyroid gland.

It has been shown that metastases to the thyroid from extrathyroidal malignancies occur as solitary or multiple nodules, or may involve the whole thyroid gland diffusely. However, diffuse metastasis of gastric cancer to the thyroid is extremely rare. Here, we report a case of a 74-year-old woman with diffuse infiltration of gastric adenocarcinoma (signet-ring-cell carcinoma/poorly differentiated adenocarcinoma) cells in the thyroid. The pathological diagnosis was made based on upper gastrointestinal endoscopy with biopsy and fine-needle aspiration cytology of the thyroid. An 18F-FDG PET/CT revealed multiple lesions with increased uptake, including the bilateral thyroid gland. On thyroid ultrasound examination, diffuse enlargement with internal heterogeneity and hypoechoic reticular lines was observed. On color Doppler imaging, a blood-flow signal was not detected in these hypoechoic lines. These findings were similar to those of diffuse metastases caused by other primary cancers, such as lung cancer, as reported earlier. Therefore, the presence of hypoechoic reticular lines without blood-flow signals is probably common to diffuse thyroid metastasis from any origin and an important diagnostic finding. This is the first report to show detailed ultrasound findings of diffuse gastric cancer metastasis to the thyroid gland using color Doppler.

[Glucagon-like peptide-1 receptor agonists].

Recently, the number of diabetic patients with obesity has increased by changes in life-style including food and physical exercise. Appearance of incretin-related drugs has given us more options for treating type 2 diabetes, and they are evaluated in regard to realizing appropriately controlled glycemic status. One of incretin-related drugs, glucagon-like peptide-1 receptor agonist (GLP-1RA), possesses pleiotropic actions to pancreatic ß/α cells and other targets, and is highly expected from the clinical aspect. Specifically, the long-acting GLP-1RAs lower fasting glucose levels, and the short-acting GLP-1RAs lower post-prandial glucose levels. By optimally employing these drugs, better glycemic management should be enabled.

One-year real-life efficacy of sitagliptin revealed importance of concomitant pioglitazone use in Japanese patients with type 2 diabetes mellitus.

AIMS: Dipeptidyl-peptidase 4 inhibitors have become one of the most popular antidiabetic drugs. However, what kind of combinations with other drugs were advantageous was not known. Here, we tried to elucidate it in a real-life clinical setting. METHODS: We retrospectively studied efficacies of sitagliptin in 87 Japanese patients with type 2 diabetes mellitus for 52 weeks. We divided subjects into excellent, effective and unresponsive subgroups according to glycemic responses to sitagliptin. RESULTS: In the excellent and effective groups the minimum HbA1c values were attained at 16 weeks while HbA1c levels in the unresponsive group kept increasing during the study period. There was a significant difference in the baseline HbA1c values between the excellent and unresponsive groups (p=0.02). Interestingly, the mean doses of pioglitazone were highest in the excellent group and lowest in the unresponsive group (p=0.02). When we compared the effective and unresponsive groups, the mean doses of sulfonylureas were constantly higher in the effective group than in the unresponsive group (p=0.05). CONCLUSIONS: These data suggest that the baseline HbA1c value can be a factor that predicts the extent of HbA1c reduction and reveal a possibility that the concomitant use of pioglitazone augments glycemic responsiveness to sitagliptin.

Critical promoter region for statin-induced human endothelial nitric oxide synthase (eNOS) transcription in EA.hy926 cells.

AIM: Statins have many anti-atherogenic effects apart from reducing the serum level of low density lipoprotein cholesterol (LDL-C). For instance, statins can enhance the expression of endothelial nitric oxide synthase (eNOS), at least partly by upregulating its transcription. Although it has been reported that -786 T/C polymorphism of the promoter region has an important influence on statininduced transcription of the human eNOS gene, much remains unclear about statin-induced eNOS transcription. We tried to identify other statin-responsive promoter regions. METHODS: A human endothelial cell line (EA.hy926 cells) was treated with pitavastatin, atorvastatin, or fluvastatin, after which eNOS mRNA levels were assessed by quantitative real-time RT-PCR. EA.hy926 cells were also transiently transfected with luciferase reporter genes driven by various lengths of the human eNOS promoter and were treated with statins before luciferase activity was measured. RESULTS: Statin treatment increased eNOS mRNA levels in EA.hy926 cells. In addition, cells transfected with the reporter gene driven by the eNOS promoter fragment starting from position -740 exhibited a pitavastatin-induced increase of luciferase activity, which was not observed in cells transfected with the reporter gene driven by the fragment starting from -727. Similar results were also obtained with atorvastatin and fluvastatin. CONCLUSIONS: Statins enhanced eNOS expression in EA.hy926 cells, at least partly by inducing its transcription. Although a statin-responsive sequence that could function even in a heterologous promoter was not precisely identified, the region of the human eNOS promoter around position -730 seems to be critical for statin-induced transcriptional activation.

Serum from methimazole-treated patients induces activation of aryl hydrocarbon receptor, a transcription factor that binds to dioxin-response elements.

BACKGROUND: The aryl hydrocarbon receptor (AhR) is a transcription factor that is activated by xenobiotic substances such as dioxin. After activation, it binds to dioxin response elements of DNA, thereby inducing transcription of a variety of xenobiotic metabolizing enzymes. To investigate whether AhR-activating substances accumulate in patients with endocrine disorders, we tested serum samples for AhR-stimulating activity. METHODS: Serum AhR-stimulating activity was evaluated by exposing the HepG2 cells transiently transfected with an AhR-responsive reporter plasmid to serum samples. On the basis of preliminary findings that implicated methimazole (MMI), wild-type and AhR-null mice were treated with MMI, and their plasma AhR-stimulating activities and thyroxine levels were quantified. RESULTS: In 28 randomly chosen patients, 7 out of 10 Graves' disease patients exhibited increased serum AhR-stimulating activity. The increased activity did not correlate with thyroid hormone status. However, we hypothesized that it might be caused by MMI. Subsequent analyses revealed that in 25 of 26 MMI-treated Graves' patients, serum samples collected after the MMI treatment had significantly higher AhR-stimulating activity compared to samples obtained when the same patients were not on MMI. By contrast, serum AhR-stimulating activity was unchanged in samples from the seven patients on propylthiouracil (PTU) compared to serum taken before the PTU treatment. In vitro experiments demonstrated that an MMI metabolite 3-methyl-2-thiohydantoin, but not MMI, activated AhR. MMI increased plasma AhR-stimulating activities and reduced plasma thyroxine concentrations, in both wild-type and AhR-deficient mice. CONCLUSIONS: Graves' patients taking MMI have increased serum AhR-stimulating activity, which is unrelated to thyroid hormone status, but correlates with MMI treatment. The AhR activation is likely caused by 3-methyl-2-thiohydantoin. Further studies are required to determine the potency of 3-methyl-2-thiohydantoin as an AhR activator and the significance of the differences between MMI and PTU observed in this study.

[Dyslipidemia].

Low-density lipoprotein (LDL) cholesterol is the most established risk factor for atherosclerotic disease such as coronary artery disease and cerebrovascular disease. High-density lipoprotein (HDL) cholesterol and nonHDL-C as well as small dense LDL, Remnant like particles cholesterol (RLP-C) and oxidized LDL are the secondary risk factors for atherosclerosis. It is important to integrate and control these risk factors for the prevention of atherosclerosis as a real endpoint of diagnosis and treatment of dyslipidemia.

Determination of immuno-reactive rabbit apolipoprotein B-48 in serum by ELISA.

Apolipoprotein B-48 (apoB-48) is produced by the small intestine, is associated with chylomicrons, and appears to be a suitable marker for clinical studies of postprandial dynamics of lipoproteins. It is also associated with cardiovascular risk factors. We have developed an assay system to quantify immuno-reactive apoB-48 in rabbit serum or plasma. A microtiter-plate was coated with monoclonal antibody raised against human apoB-48 C-terminal specific decapeptide that has high homology to the rabbit C-terminal sequence. Appropriate ELISA standard curves were obtained using apoB-48 extracted from rabbit serum by immuno-affinity chromatography. No cross-reactivity was found with apoB-100 in western blot analyses. Intra- and inter-assay CVs were less than 3%. Recovery of rabbit apoB-48 spiked in serum was within 93.4-105%. ApoB-48 levels in healthy controls rabbits fed a normal diet were within the range of 0.903-1.09 microg/ml (mean +/- SD: 1.03 +/- 0.084 microg/ml). In healthy animals, the blood apoB-48 level was markedly increased by a high fat diet and in the postprandial state in parallel with serum triglyceride. Ezetimibe, cholesterol absorption inhibitor, given orally to rabbits fed on a high fat diet blocked further increase of blood levels of apoB-48 and triglyceride. This method for measuring apoB-48 using the monoclonal antibody is simple, reliable, and suitable for routine analyses.

A SNP of NPC1L1 affects cholesterol absorption in Japanese.

AIM: Ezetimibe is known to target Niemann-Pick Type C1 Like1 (NPC1L1), a key protein in intestinal cholesterol absorption, and thus to decrease serum LDL-cholesterol (LDL-C) levels. The response of serum LDL-C levels to ezetimibe was reported to differe among NPC1L1 haplotypes.We analyzed NPC1L1 genotypes in Japanese and investigated differences in markers of cholesterol synthesis/absorption among the genotypes. METHODS: Blood samples were collected from 42 adult volunteers to measure markers of cholesterol synthesis (lathosterol) and absorption (sitosterol and campesterol) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Based on a study by Hegele RA et al. in Canada, we selected three SNPs (1735 C>G, 25342 A>C and 27677 T>C (numbers relative to the transcription start site)) and analyzed them using PCR-RFLP. RESULTS: The frequencies of genotypes were as follows: 1735 C/G (46%)>C/C (35%)>G/G (19%), 25342 A/A (97%)>A/C (3%)>C/C (0%) and 27677 T/T (97%)>T/C (3%)>C/C (0%). Serum campesterol levels were significantly higher in the 1735 G/G group than 1735 C/G+C/C group, but lathosterol levels showed no significant differences between the genotypes. CONCLUSION: Our results revealed differences in the frequency of the NPC1L1 polymorphism between Japanese and Canadians. In Japanese, the 1735 G/G group showed enhanced cholesterol absorption from the intestine, as compared to the 1735 C/G+C/C group.

Increased serum apolipoprotein B48 concentration in patients with metabolic syndrome.

AIM: Postprandial hyperlipidemia is characterized by an increase of chylomicron remnants (CM-R), and is a risk factor for atherosclerosis. Apolipoprotein (apo) B48 exists exclusively in chylomicroms and CM-R, and fasting plasma levels of apo B48 may reflect high postprandial levels of chylomicrons and/or CM-R. We hypothesized that fasting apo B48 levels may be increased in metabolic syndrome. METHODS: We investigated 1,349 inhabitants (528 men and 821 women aged 62.4+/-12.8 y; mean+/-S.D.) of two towns in rural Hokkaido, who underwent health checks in 2005. RESULTS: The fasting apo B48 level was significantly higher in males than females (geometric mean 1.92; 95% CI 1.802.04 microg/mL, vs. 1.69; 95% CI 1.611.76 microg/mL; p< 0.001). Ln (apo B48) showed a significant positive correlation with total cholesterol and ln (triglycerides), and a negative correlation with HDL-cholesterol. The correlation between ln (apo B48) and ln (triglycerides) was strong. Apo B48 was significantly higher in men and women with than without metabolic syndrome. Regression analysis revealed that ln (apo B48) was significantly associated with age, BMI, total cholesterol, HDL cholesterol, LDL cholesterol, and ln (triglyceride). CONCLUSION: Fasting apo B48 levels are raised in individuals with metabolic syndrome.