Hereditary transthyretin (ATTRv) amyloidosis, also known as familial amyloid polyneuropathy (FAP), is a disease caused by the systemic deposition of variant transthyretin (TTR). Although this disease was primarily indigenous to endemic foci in Portugal, Japan, and Sweden, its prevalence has increased throughout the world. Val30Met, one of the most common TTR mutations, exhibits varying characteristic features in the early-onset patients from conventional endemic foci and the late-onset patients from non-endemic areas. Severe autonomic dysfunctions and dissociated sensory loss are the characteristic features of the former, whereas mild autonomic dysfunctions and loss of all sensory modalities are observed in the latter. Distortion and atrophy of the Schwann cells due to the formation of amyloid fibrils seem to cause predominant small-fiber loss in the early-onset patients, while other mechanisms, such as microangiopathy and the toxicity of TTR oligomers, may contribute to nerve fiber loss in the late-onset patients.
Recently novel therapies had been applied to several types of amyloidosis such as hereditary transthyretin (ATTR, ATTRv) amyloidosis, ATTRwt amyloidosis, AL amyloidosis, and AA amyloidosis. Type and manifestations of amyloidosis were diverse. For early diagnosis and appropriate intervention, more enlightenment activities and more development of diagnosis systems for amyloidosis are needed.
Amyloidosis used to be an untreatable disease with poor prognosis. Recently, however, disease modifying therapies based on the pathogenesis have been developed in succession. Liver transplantation is an established therapy for hereditary ATTR amyloidosis, however, it still has problems, such as its invasiveness and progression of amyloidosis after transplantation. Recently, clinical effects of TTR tetramer stabilizers (i.e., tafamidis and diflunisal) and oligonucleotide therapeutics (i.e., patisiran and inotersen), were demonstrated in randomised clinical trials, and tafamidis and patisiran were approved for treatment of hereditary ATTR amyloidosis in Japan. In addition, indication of tafamidis was expanded to wild-type ATTR amyloidosis in 2019. Concerning AL amyloidosis, several novel chemotherapies target for bone marrow abnormal plasma cell have been developed, resulting in improved prognosis of the disease.
Oxytocin (OXT) is involved in not only parturition and the milk ejection reflex, but also various functions such as regulation of anti-nociception, anxiety, trust, bonding, social recognition, and maintenance of bone and skeletal muscle. We examined the age-related changes of OXT in the posterior pituitary (PP), the supraoptic nucleus (SON) and the paraventricular nucleus (PVN), using a transgenic rat line that expresses the oxytocin-monomeric red fluorescent protein 1 (mRFP1) fusion gene, and investigated the relations of OXT and aging in the hypothalamo-neurohypophysial system. For the future, understanding the association between OXT and aging will be important for developing interventions for sarcopenia and loneliness/social isolation among older adults. In this paper, we review the role of OXT in the context of age-related changes, social function and anti-nociception, and maintenance of bone and skeletal muscle.
Neuronal intranuclear inclusion disease (NIID) is a rare progressive neurodegenerative disorder characterized by eosinophilic hyaline intranuclear inclusions in neuronal and somatic cells. Clinically the disease occurs in adult with any combination of progressive dementia, cerebellar ataxia and motor-sensory and autonomic neuropathy. Bladder dysfunctions are occurred about 30 % in sporadic cases and 60% in familial cases. The results of urodynamic study showed that bladder sensory dysfunction and underactive detrusor at first. The results of urodynamic study showed that bladder sensory disorder and detrusor overactivity in the second examination. NIID might be caused by peripheral and central nervous system dysfunction. For managing bladder dysfunction in neurologic patients including NIID, it is important not only to address functional incontinence due to dementia and immobility. Thus, checking post-void residual (PVR) is recommended for treatments.
The purpose of this study was the effect of periocular thermotherapy on the choroid. Our subjects were 20 healthy volunteers. We used a heatable steam eye mask with a wet heat of 40℃, which was worn for a period of 10 minutes. Using optical coherence tomography (OCT), choroidal tomography was performed: before heating, immediately after heating, and 10 minutes after heating. At the same time, the pupil was used to measure the autonomic response, and the visual analogue scale was used to measure eye fatigue. The OCT image is subjected to binarization processing, and the choroid area (C) and luminal area (L) were identified. C and L were both increased immediately after heating compared to before (C: p<0.05; L: p<0.01). In addition, the increase in C and L persisted 10 minutes after heating compared to before heating (p<0.05). The pupil exhibited miosis immediately after and 10 minutes after heating compared to before (p<0.01).The eye fatigue decreased after heating compared to before heating (p<0.01). The periocular thermotherapy increased the choroid area by activating the parasympathetic nerve through the somatosensory.
We investigated the effects of tinted lenses’ color on the autonomic nervous system, based on pupil diameter and heart rate variability. The study participants were 14 healthy young adults. For the tinted lenses, three colors were selected: green, grey, and orange. Examinations were performed in a dark adaptation room. The participants were in a supine position and were asked to look fixedly at a cross marked in the center of a white background on a luminescent display (9.7-inch iPad) positioned 30 cm from their eyes. Pupil diameter and heart rate variability were measured with an infrared pupilometer (Newopto Corp.) and a Reflex Meijin system (Crosswell Co., Ltd.), respectively, before, during, and after wearing the tinted lenses. Pupil constriction after lens-wearing compared with lens-wearing was induced by the three tinted lenses, and after green lens-wearing, pupil was greater than before lens-wearing. Pupil dilation during lens-wearing compared with before lens-wearing was induced by the orange tinted lens. Heart rate variability analysis revealed no significant differences between the before, during, and after lens-wearing periods for any color. The color of the tinted lenses induced changes in pupil diameter but had no effect on heart rate variability.
One hundred thirty-five physically healthy women aged 45–55 years without organic disease were divided into three groups BMI<18.5, 18.5≤BMI<25.0, 25.0≤BMI<30, the BMI classification used by the Japan Society for the Study of Obesity (JASSO). Their heart rate variability (HRV) was evaluated by the active tracer measurement method during supine rest, ergometer testing and post-ergometer sitting. There were no significant differences in HRV during rest and ergometer testing among three groups, but during post ergometer sitting the 25.0≤BMI<30 group showed a significantly higher HRV (CVRR, SDNN, LF and HF) than the other two groups, and the BMI<18.5 group showed a significantly lower HRV than the 25.0≤BMI<30 group during post ergometer sitting with a LF component that was remarkably lower than other two groups. In conclusion, from the standpoint of HRV activity, middle-aged women without organic disease and BMI<18.5 need careful examination and follow up.
A 69-year-old man noticed unsteadiness of gait from 2006, and was diagnosed as having multiple systems atrophy (MSA-C) in 2008 since cerebellar ataxic and static hypotension was found in addition to characteristic MRI findings. In January 2018, because of clouding of consciousness and a temperature of 32.2 degrees, he was admitted to another hospital. The clouding of consciousness and hypothermia immediately improved on general warming. Because clouding of consciousness and hypothermia also occurred in March, he was admitted to our hospital for further examination. On admission, he had cerebellar dysarthria, walking disability due to incoordination of the limbs and urinary incontinence. CVR-R was normal, and a sympathetic skin response was not confirmed. The baselines of skin blood flow in his upper limbs were high, and a blood flow decrease response was not confirmed on electrical stimulation, but was confirmed on deep breathing. Thermography showed the temperature of his upper limbs was relatively high, but his trunk temperature was low. This case had MSA-C with Shapiro's syndrome, and since the patient's skin blood volume of the upper limbs was elevated and the skin temperature was high, but there was little skin blood flow decrease reactions, it was speculated that repeated hypothermia may have occurred because his body temperature was easily influenced by the outside temperature.