Acquired Thrombotic Thrombocytopenic Purpura Following BNT162b2 mRNA Coronavirus Disease Vaccination in a Japanese Patient

A 57-year-old man without underlying diseases presented with fatigue, loss of appetite, and jaundice 1 week after receiving the first dose of the BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine and showed hemolytic anemia with fragmented erythrocytes and severe thrombocytopenia 2 weeks after receiving the vaccine. An a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) activity level of <10% and ADAMTS13 inhibitor positivity confirmed the diagnosis of acquired thrombotic thrombocytopenic purpura (TTP). Combination therapy with plasma exchange, corticosteroid, and rituximab improved the clinical outcome. We herein report the first Japanese case of TTP possibly associated with vaccination. Physicians should be alert for this rare but life-threatening hematological complication following COVID-19 vaccination.     

Preparation of a platinum nanoparticle catalyst located near photocatalyst titanium oxide and its catalytic activity to convert benzyl alcohols to the corresponding ethers

A novel platinum nanoparticle catalyst closely located near the surface of titanium oxide, PtNP/TiO₂, has been prepared. This catalyst has both the properties of a photocatalyst and a metal nanoparticle catalyst, and acquired environmentally friendly catalytic activity, which cannot be achieved by just one of these catalysts, to afford ethers from benzyl alcohols under the wavelength of 420 nm.

A novel platinum nanoparticle catalyst closely located near the surface of titanium oxide, PtNP/TiO₂, has been prepared. It has catalytic activity to afford ethers from benzyl alcohols under the wavelength of 420 nm.

The electrolysis of water by a heterogeneous metal oxide semiconductor (MOS) photocatalyst, called the Honda–Fujishima effect,¹ received considerable attention because it enables the conversion of solar energy. As a result, photoreactions by heterogeneous photocatalysts based on MOS have been reported until now, including numerous practical applications such as carbon dioxide reduction² and pollutant removal.³Research on photocatalytic reactions using visible light is progressing steadily. Among them, TiO₂ has been extensively studied due to its high catalytic activity, low cost, non-toxicity, and long-term stability.^4,5Titanium oxide has a very strong oxidizing power, but it does not have a strong reducing power.⁶ By using a transition metal such as platinum on titanium oxide as a support, its reducing power can be increased, and the amount of hydrogen generated in the electrolysis of water can be improved eight times compared to the case of titanium oxide alone.⁷Furthermore, when MOS contacts the metal, a potential barrier called Schottky barrier is formed at the interface. The basic characteristic of this Schottky barrier lies in the Schottky barrier height (Φ), which represents the difference between the CB of the MOS distorted by the contact with a metal and the Fermi level (E_F) of the metal. Although it has been studied for almost half a century, how to determine the barrier is still not well understood. Due to the formation of the Schottky barrier height, the energy required to move the electrons from the valence band of MOS to the conductor changes from E_g to Φ, and the energy becomes smaller and it changes to a longer wavelength. As a result, a photoreaction with titanium oxide using light with a wavelength longer than 387 nm has also been reported (Scheme 1)⁸Open in a separate windowScheme 1Effect of sunlight exposure on aerobic oxidation of alcohols with the Pt/TiO₂ catalysts.On the other hand, we have recently developed a sulfur-modified Au-supported Pd NP catalyst (SAPd) that is applicable in Suzuki–Miyaura coupling^9a,9b and C–H functionalization^9c (Scheme 2a). It was constructed by approximately 10 layers of self-assembled Pd(0) NPs (mean size: <5 nm) supported on a sulfur-modified Au surface. We speculated that the self-assembled Pd NPs, which were encapsulated in a sulfated p-xylene polymer matrix,^9d were formed using in situ metal NP and nanospace simultaneous organization (PSSO), as illustrated in Scheme 2b: (i) the reduction of a high-valence metal source, (ii) growth of transition metal NPs, (iii) growth of a matrix with appropriately sized nanopores, and (iv) encapsulation of the metal NPs in these nanopores. To prepare SARu,¹⁰ SANi,¹¹ SAFe(ii),¹² and SAFe(0)¹³ (Scheme 2a), the PSSO method involves the in situ reduction of a noble metal precursor to produce in situ metal NPs.Open in a separate windowScheme 2(a) Preparation of SAPd, SARu, SANi, SAFe(II) and SAFe(0) by combining in situ PSSO with an organic reductant, (b) in situ metal nanoparticle and nanospace simultaneous organization (PSSO) method and the image of the SAPd structure and (c) the preparation of PtNP/TiO₂.In this research project, we decided to create a novel metal NP catalyst having metal NPs near the surface of TiO₂ by substituting the gold-supported SAPd for gold with a titanium oxide (TiO₂) photocatalyst. Alternatively, by substituting the solid gold support for a photocatalyst, we thought that we could create a novel metal NPs catalyst with an unprecedented reactivity by combining the properties of both photocatalyst and metal nanoparticle catalyst (Scheme 2c).     

Parallel enlargement of Marinesco bodies and nuclei and progressive deposition of p62 in pigmented neurons of the substantia nigra

Marinesco bodies (MBs) are spherical nuclear inclusions found in pigmented neurons of the substantia nigra. Although MBs are abundant in senescent brains, how they are related to aging processes remains unclear. Here, we performed a morphometric analysis of midbrain pigmented neurons to identify the possible influence of MBs on nuclear size. The transected area of the nucleus (nuclear area) was larger in the presence of MBs and was correlated with the area of MB (MB area) in all tested brains. The MB-associated nuclear enlargement was significant even after MB areas were subtracted from nuclear areas. Moreover, higher MB immunoreactivity of p62 was detected in the nucleoplasm of the enlarged MB-associated nuclei. This study on human brains is the first quantitative approach demonstrating MB-associated nuclear enlargement and progressive accumulation of small nucleoplasmic materials. Although cellular hypertrophy is usually considered to be an indication of the upregulation of cellular function, this might not always be the case. These findings suggest that an age-related decline of ubiquitin-proteasome and autophagy system activity and stagnation of undegradable materials are one of the candidate mechanisms to explain the age-related decline of neural activity in the substantia nigra.     

Definite familial multiple system atrophy with unknown genetics

Multiple system atrophy (MSA) is an oligodendrogliopathy of presumably sporadic origin, characterized by prominent α‐synuclein inclusions with neuronal multisystem degeneration, although a few Mendelian pedigrees have been reported. Here we report two familial cases of MSA of unknown genetic background. One patient was diagnosed as a possible MSA‐C (cerebellar dysfuntion) case, and the other as clinically possible MSA‐P (parkinsonism), which turned out to be definite MSA, based on a detailed autopsy. The neuropathology showed extensive deposition of α‐synuclein in the glia as well as in the neurons located in the cerebral cortices and hippocampal systems, although neither multiplication of the SNCA gene or mutations in COQ2 gene were identified in the family concerned.     

Specific Detection of Pathological Three‐repeat Tau after Pretreatment with Potassium Permanganate and Oxalic Acid in PSP/CBD Brains

Immunohistochemisty with RD3, a monoclonal antibody specific for three‐repeat (3R) tau, is sometimes hampered by diffuse neuronal staining on formalin‐fixed, paraffin‐embedded sections pretreated with formic acid and heating. Additional pretreatment with potassium permanganate followed by oxalic acid completely eliminated this diffuse RD3‐immunoreactivity (IR) in neurons. Furthermore, this additional pretreatment uniformly enhanced RD3‐IR, as well as RD4‐IR, a monoclonal antibody specific for four‐repeat (4R) tau, on pathological deposits with tau IR. This enhanced sensitivity and specificity may allow more reliable identification of 3R and 4R tau in pathological deposits, which may be variable dependent on disease and regions. Cerebral cortex and midbrain from 8 patients [5 progressive supranuclear palsy (PSP) and 3 corticobasal degeneration (CBD)] were screened for RD3‐ and RD4‐IR with this improved procedure. In addition to RD4‐positive structures found both in cerebral cortex and brainstem, RD3‐positive neurofibrillary tangles (NFTs) were also found in midbrain in 7 of these 8 cases but not in the cortex. Multi‐labeling study demonstrated that most of RD3‐negative neurons were positive for RD4. This reliable demonstration of pathological 3R tau deposits in the brainstem of PSP/CBD, so far presumably characterized by deposition of 4R tau, is useful to map tau‐positive lesions according to their biochemical composition.     

Anti-ageing effects of dentifrices containing anti-oxidative,anti-inflammatory,and anti-bacterial agents (Tomarina) on gingival collagen degradation in rats

Objective

Previous studies have demonstrated the relationship between ageing and oxidative stress. In this study, we examined the effects of topical application of a dentifrice containing anti-oxidative, anti-inflammatory, and anti-bacterial agents (Tomarina^®) to the gingival surface on gingival collagen degradation in rats.

Design

Fischer 344 male rats (4 or 8 months old) were divided into two groups: experimental group and control group. Tomarina^® (the experimental group) or control dentifrice (the control group) was applied 5 days per week for 2 months.

Results

In the control group, gingival collagen density decreased with ageing. In the experimental group, the collagen density did not change with ageing, and was greater than that in the control group at 10 months of age (p < 0.0083). In addition, the control group showed an increase in serum oxidative stress with ageing. The experimental group also showed increased serum oxidative stress, but the value was lower than the control group at 10 months of age (p < 0.0083). Furthermore, low expressions of protein oxidative damage in the periodontal tissue were observed in the experimental group, compared to the control group at 6 months and 10 months.

Conclusion

These findings indicate that Tomarina^® might suppress the effects of ageing on gingival collagen degradation, by decreasing oxidative stress in the rat model.     

Comparison of valsartan and amlodipine on ambulatory blood pressure variability in hypertensive patients

We tested the hypothesis that calcium channel blockers (CCBs: amlodipine group, n = 38)) are superior to angiotensin receptor blockers (ARBs: valsartan group, n = 38) against ambulatory blood pressure variability (BPV) in untreated Japanese hypertensive patients. Both drugs significantly reduced ambulatory systolic and diastolic BP values. With regard to BPV, standard deviation (SD) in SBP did not change with the administration of either drug, but the ARB significantly increased SD in awake DBP (12 ± 4–14 ± 4 mmHg). The ARB also significantly increased the coefficients of variation (CVs)in awake and 24-h SBP/DBP (all P < 0.05), but amlodipine did not change the CV. CCB significantly reduced the maximum values of awake SBP (193 ± 24–182 ± 27 mmHg, P = 0.02), sleep SBP (156 ± 18–139 ± 14 mmHg, P < 0 .001), and awake and sleep DBP (P < 0.01 in both cases), but the ARB did not change the maximum BP values. In conclusion, a once-daily morning dose of CCB amlodipine was more effective at controlling ambulatory BPV than ARB valsartan, especially in reducing maximum BP levels.     

Comparison of Local Recurrence in Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma with Or Without Accumulation of Iodized Oil Beyond Corona Enhancement Area: Short-term Results

BackgroundLocal tumor recurrence of hepatocellular carcinoma (HCC) often occurs in blood drainage areas. Corona enhancement is determined by computed tomography during hepatic arteriography (CTHA) and is considered to represent the blood drainage area. This study aimed to investigate the relationship between embolization of corona enhancement area and local tumor recurrence of patients with HCC who underwent transcatheter arterial chemoembolization (TACE).Patients and methodsThe study retrospectively selected 53 patients with 60 HCC nodules that showed corona enhancement area on late-phase CTHA and showed homogenous accumulation of iodized oil throughout the nodule on non-contrast-enhanced CT performed immediately after TACE. We divided the nodules into two groups, according to whether the accumulation of iodized oil covered the entire corona enhancement area (group A) or not (group B). Local tumor recurrence was compared between the two groups.ResultsThe cumulative local tumor recurrence rates for group A (n = 36) were 2.8%, 2.8%, 8.3% at 3, 6, and 12 months, respectively, whereas the recurrence rates for group B (n = 24) were 20.8%, 45.8%, 75% at 3, 6, and 12 months, respectively. The cumulative local tumor recurrence rates for group A were significantly lower than those for group B (hazard ratio, 0.079; 95% confidence interval, 0.026–0.24; p < 0.001).ConclusionsThe results of the study suggest that the corona enhancement area may be an accurate safety margin in TACE which should be performed until the embolic area covers the entire corona enhancement area.Key words: corona enhancement, transcatheter arterial chemoembolization, computed tomography during hepatic arteriography, hepatocellular carcinoma