Interictal epileptiform discharges as a predictive biomarker for recurrence of poststroke epilepsy.

Poststroke epilepsy is a major ischaemic/haemorrhagic stroke complication. Seizure recurrence risk estimation and early therapeutic intervention are critical, given the association of poststroke epilepsy with worse functional outcomes, quality of life and greater mortality. Several studies have reported risk factors for seizure recurrence; however, in poststroke epilepsy, the role of EEG in predicting the risk of seizures remains unclear. This multicentre observational study aimed to clarify whether EEG findings constitute a risk factor for seizure recurrence in patients with poststroke epilepsy. Patients with poststroke epilepsy were recruited from the PROgnosis of POst-Stroke Epilepsy study, an observational multicentre cohort study. The enrolled patients with poststroke epilepsy were those admitted at selected hospitals between November 2014 and June 2017. All patients underwent EEG during the interictal period during admission to each hospital and were monitored for seizure recurrence over 1 year. Board-certified neurologists or epileptologists evaluated all EEG findings. We investigated the relationship between EEG findings and seizure recurrence. Among 187 patients with poststroke epilepsy (65 were women with a median age of 75 years) admitted to the lead hospital, 48 (25.7%) had interictal epileptiform discharges on EEG. During the follow-up period (median, 397 days; interquartile range, 337-450 days), interictal epileptiform discharges were positively correlated with seizure recurrence (hazard ratio, 3.82; 95% confidence interval, 2.09-6.97; P < 0.01). The correlation remained significant even after adjusting for age, sex, severity of stroke, type of stroke and generation of antiseizure medications. We detected periodic discharges in 39 patients (20.9%), and spiky/sharp periodic discharges were marginally associated with seizure recurrence (hazard ratio, 1.85; 95% confidence interval, 0.93-3.69; P = 0.08). Analysis of a validation cohort comprising 187 patients with poststroke epilepsy from seven other hospitals corroborated the association between interictal epileptiform discharges and seizure recurrence. We verified that interictal epileptiform discharges are a risk factor for seizure recurrence in patients with poststroke epilepsy. Routine EEG may facilitate the estimation of seizure recurrence risk and the development of therapeutic regimens for poststroke epilepsy.

Persistent brain damage in reversible cerebral vasoconstriction syndrome on 99mTc-ethyl cysteinate dimer single-photon emission computed tomography: A long-term observational study.

BACKGROUND: Blood-brain barrier (BBB) breakdown is considered a key step in the pathophysiology of reversible cerebral vasoconstriction syndrome (RCVS); however, its temporal course remains unclear. Based on the characteristics and dynamics of 99mTc-ethyl cysteinate dimer (99mTc-ECD) as a tracer, 99mTc-ECD single-photon emission computed tomography (SPECT) can detect not only hypoperfusion but also BBB breakdown and/or brain tissue damage. Therefore, this study aimed to investigate this course using 99mTc-ECD SPECT. METHODS: Between 2011 and 2019, we enrolled seven patients (one male and six female patients) with RCVS without ischemic or hemorrhagic stroke or posterior reversible encephalopathy syndrome. 99mTc-ECD SPECT was performed repeatedly in each patient. SPECT data were statistically analyzed using an easy Z-score imaging system. RESULTS: Thunderclap headache was the initial symptom in all the patients and was most commonly triggered by bathing (three patients). All the patients exhibited vasoconstriction and reduced cerebral uptake of 99mTc-ECD during the acute stage. Follow-up assessment from 3 to 16 months showed that reduced cerebral uptake persisted in all the patients, even after the vasoconstriction had resolved. CONCLUSION: Reduced cerebral uptake of 99mTc-ECD persisted in the late stage of RCVS, even after vasoconstriction and headache subsided. BBB breakdown and/or brain tissue damage may underlie this phenomenon. 99mTc-ECD SPECT is an effective neuroimaging method to detect brain functional abnormalities, reflecting BBB breakdown or tissue damages, throughout the treatment course of RCVS.

Posterior reversible encephalopathy syndrome presenting with thrombotic microangiopathy triggered by malignant hypertension: a case report and literature review.

Background: Posterior reversible encephalopathy syndrome (PRES) is a disease characterised by reversible subcortical vasogenic oedema, neurological symptoms and abnormal findings on head imaging. It is recognised as one of the most prominent organ disorders in hypertensive emergencies but is rarely associated with thrombotic microangiopathy (TMA). Case presentation: A woman in her 40s with untreated hypertension had occasional headaches in the past 4 months. The headaches worsened during the 3 weeks prior to admission. On the day of admission, the patient presented with severe headache accompanied by frequent vomiting. MRI of the head revealed oedematous changes in the brainstem, including the subcortical, cerebellum and pons. Fundus examination revealed hypertensive retinopathy with papilloedema. Blood tests indicated thrombocytopenia, renal dysfunction and haemolytic anaemia, and a blood smear confirmed fragmented erythrocytes. Coombs' test, and tests for ADAMTS13 activity and infectious and autoimmune diseases were negative. The patient was diagnosed with PRES, secondary to malignant hypertension (MH) and associated with TMA. Antihypertensive therapy promptly improved the clinical symptoms, blood pressure, and the abnormal MRI and blood test findings. The patient was discharged from the hospital 20 days after admission. Conclusions: We report a rare case of PRES that was associated with TMA and triggered by MH. Antihypertensive therapy was effective in alleviating the associated adverse clinical symptoms. Differentiation of underlying diseases is essential for early intervention, since treatment depends on factors causing TMA.

Impact of Seizure Recurrence on 1-Year Functional Outcome and Mortality in Patients With Poststroke Epilepsy.

BACKGROUND AND OBJECTIVES: The functional outcome and mortality of patients with poststroke epilepsy (PSE) have not been assessed in a prospective study. Previous reports have suggested that patients with PSE may suffer from prolonged functional deterioration after a seizure. In this study, we prospectively investigated the functional outcome and mortality of patients with PSE and analyzed the effect of seizure recurrence on the outcomes. METHODS: This is part of the Prognosis of Post-Stroke Epilepsy study, a multicenter, prospective observational cohort study, where 392 patients with PSE (at least 1 unprovoked seizure more than 7 days after the onset of the last symptomatic stroke) were followed for at least 1 year at 8 hospitals in Japan. This study included only PSE patients with a first-ever seizure and assessed their functional decline and mortality at 1 year. Functional decline was defined as an increase in modified Rankin Scale (mRS) score at 1 year compared with baseline, excluding death. The associations between the seizure recurrence and the outcomes were analyzed statistically. RESULTS: A total of 211 patients (median age of 75 years; median mRS score of 3) were identified. At 1 year, 50 patients (23.7%) experienced seizure recurrence. Regarding outcomes, 25 patients (11.8%) demonstrated functional decline and 20 (9.5%) had died. Most patients died of pneumonia or cardiac disease (7 patients each), and no known causes of death were directly related to recurrent seizures. Seizure recurrence was significantly associated with functional decline (odds ratio [OR] 2.96, 95% CI 1.25-7.03, p = 0.01), even after adjusting for potential confounders (adjusted OR 3.26, 95% CI 1.27-8.36, p = 0.01), but not with mortality (OR 0.79, 95% CI 0.25-2.48, p = 0.68). Moreover, there was a significant trend where patients with more recurrent seizures were more likely to have functional decline (8.7%, 20.6%, and 28.6% in none, 1, and 2 or more recurrent seizures, respectively; p = 0.006). DISCUSSION: One-year functional outcome and mortality of patients with PSE were poor. Seizure recurrence was significantly associated with functional outcome, but not with mortality. Further studies are needed to ascertain whether early and adequate antiseizure treatment can prevent the functional deterioration of patients with PSE.

S-1-Propenylcysteine promotes IL-10-induced M2c macrophage polarization through prolonged activation of IL-10R/STAT3 signaling.

Atherosclerosis is a chronic inflammatory disease that may lead to the development of serious cardiovascular diseases. Aged garlic extract (AGE) has been reported to ameliorate atherosclerosis, although its mode of action remains unclear. We found that AGE increased the mRNA or protein levels of arginase1 (Arg1), interleukin-10 (IL-10), CD206 and hypoxia-inducible factor 2α (HIF2α) and decreased that of CD68, HIF1α and inducible nitric oxide synthase in the aorta and spleen of apolipoprotein E knockout mice. We also found that S-1-propenylcysteine (S1PC), a characteristic sulfur compound in AGE, increased the level of IL-10-induced Arg1 mRNA and the extent of M2c-like macrophage polarization in vitro. In addition, S1PC increased the population of M2c-like macrophages, resulting in suppressed the population of M1-like macrophages and decreased lipopolysaccharide-induced production of pro-inflammatory cytokines. These effects were accompanied by prolonged phosphorylation of the IL-10 receptor α (IL-10Rα) and signal transducer and activator of transcription 3 (STAT3) that inhibited the interaction between IL-10Rα and Src homology-2-containing inositol 5'-phosphatase 1 (SHIP1). In addition, administration of S1PC elevated the M2c/M1 macrophage ratio in senescence-accelerated mice. These findings suggest that S1PC may help improve atherosclerosis due to its anti-inflammatory effect to promote IL-10-induced M2c macrophage polarization.

Palinopsia as an initial symptom of cerebral amyloid angiopathy-related inflammation.

•We report the first case of cerebral amyloid angiopathy-related inflammation (CAA-RI) presenting palinopsia initially.•Palinopsia is generally caused by intracranial diseases involving the parietal and occipital areas.•CAA dominantly affects parietal and occipital lobes, therefore palinopsia could be an important phenomenon of the disease.

Antiseizure medications for post-stroke epilepsy: A real-world prospective cohort study.

BACKGROUND AND PURPOSE: The management of post-stroke epilepsy (PSE) should ideally include prevention of both seizure and adverse effects; however, an optimal antiseizure medications (ASM) regimen has yet been established. The purpose of this study is to assess seizure recurrence, retention, and tolerability of older-generation and newer-generation ASM for PSE. METHODS: This prospective multicenter cohort study (PROgnosis of Post-Stroke Epilepsy [PROPOSE] study) was conducted from November 2014 to September 2019 at eight hospitals. A total of 372 patients admitted and treated with ASM at discharge were recruited. Due to the non-interventional nature of the study, ASM regimen was not adjusted and followed standard hospital practices. The primary outcome was seizure recurrence in patients receiving older-generation and newer-generation ASM. The secondary outcomes were the retention and tolerability of ASM regimens. RESULTS: Of the 372 PSE patients with ASM at discharge (median [IQR] age, 73 [64-81] years; 139 women [37.4%]), 36 were treated with older-generation, 286 with newer-generation, and 50 with mixed-generation ASM. In older- and newer-generation ASM groups (n = 322), 98 patients (30.4%) had recurrent seizures and 91 patients (28.3%) switched ASM regimen during the follow-up (371 [347-420] days). Seizure recurrence was lower in newer-generation, compared with the older-generation, ASM (hazard ratio [HR], 0.42, 95%CI 0.27-0.70; p = .0013). ASM regimen withdrawal and change of dosages were lower in newer-generation ASM (HR, 0.34, 95% CI 0.21-0.56, p < .0001). CONCLUSIONS: Newer-generation ASM possess advantages over older-generation ASM for secondary prophylaxis of post-stroke seizures in clinical practice.

S-1-propenylcysteine improves TNF-α-induced vascular endothelial barrier dysfunction by suppressing the GEF-H1/RhoA/Rac pathway.

BACKGROUND: Vascular endothelial barrier function is maintained by cell-to-cell junctional proteins and contributes to vascular homeostasis. Various risk factors such as inflammation disrupt barrier function through down-regulation of these proteins and promote vascular diseases such as atherosclerosis. Previous studies have demonstrated that aged garlic extract (AGE) and its sulfur-containing constituents exert the protective effects against several vascular diseases such as atherosclerosis. In this study, we examined whether AGE and its sulfur-containing constituents improve the endothelial barrier dysfunction elicited by a pro-inflammatory cytokine, Tumor-necrosis factor-α (TNF-α), and explored their mode of action on TNF-α signaling pathway. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with test substances in the presence of TNF-α for various time periods. The endothelial permeability was measured by using a transwell permeability assay. The localization of cell-to-cell junctional proteins and actin cytoskeletons were visualized by immunostaining. RhoA and Rac activities were assessed by using GTP-binding protein pulldown assay. Gene and protein expression levels of signaling molecules were analyzed by real-time PCR and western blotting, respectively. RESULTS: We found that AGE and its major sulfur-containing constituent, S-1-propenylcysteine (S1PC), reduced hyperpermeability elicited by TNF-α in HUVECs. In addition, S1PC inhibited TNF-α-induced production of myosin light chain (MLC) kinase and inactivation of MLC phosphatase through the suppression of the Rac and RhoA signaling pathways, respectively, which resulted in the dephosphorylation of MLC2, a key factor of actin remodeling. Moreover, S1PC inhibited the phosphorylation and activation of guanine nucleotide exchange factor-H1 (GEF-H1), a common upstream key molecule and activator of Rac and RhoA. These effects of S1PC were accompanied by its ability to prevent the disruption of junctional proteins on the cell-cell contact regions and the increase of actin stress fibers induced by TNF-α. CONCLUSIONS: The present study suggested that AGE and its major constituent, S1PC, improve endothelial barrier disruption through the protection of junctional proteins on plasma membrane. Video abstract.

S -1-Propenylcysteine, a sulfur compound in aged garlic extract, alleviates cold-induced reduction in peripheral blood flow in rat via activation of the AMPK/eNOS/NO pathway.

Aged garlic extract (AGE) has been shown to improve peripheral circulatory disturbances in both clinical trials and experimental animal models. To investigate the effect of S-1-propenylcysteine (S1PC), a characteristic sulfur compound in AGE, on cold-induced reduction in tail blood flow of rat, Wistar rats were individually placed in a restraint cage and given the treatment with cold water (15˚C) after the oral administration of AGE or its constituents S1PC, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC). After the cold-treatment the tail blood flow of rats was measured at the indicated times. The pretreatment with AGE (2 g/kg BW) and S1PC (6.5 mg/kg BW) significantly alleviated the reduction of rat tail blood flow induced by cold treatment. The effect of S1PC was dose-dependent and maximal at the dose of 6.5 mg/kg BW, whereas SAC and SAMC were ineffective. To gain insight into the mechanism of S1PC action, the concentration of nitrogen oxide metabolites (NOx) in the plasma and the levels of phosphorylated endothelial nitric oxide synthase (eNOS) and 5'-AMP-activated protein kinase (AMPK) in the aorta were measured. The pretreatment with S1PC significantly increased the plasma concentration of NOx as well as the level of phosphorylated form of AMPK and eNOS in the aorta after cold-treatment. The present findings suggest that S1PC is a major constituent responsible for the effect of AGE to alleviate the cold-induced reduction of peripheral blood flow in rat by acting on the AMPK/eNOS/NO pathway in the aorta.

Mechanisms underlying the attenuation of chronic inflammatory diseases by aged garlic extract: Involvement of the activation of AMP-activated protein kinase.

AMP-activated protein kinase (AMPK) is an ubiquitously expressed serine/threonine kinase and an important regulator of energy metabolism. The decreased activity of AMPK induced by low-grade chronic inflammation has been implicated in several diseases, including type 2 diabetes and atherosclerosis. However, the activation of AMPK by natural and synthetic products can ameliorate these diseases through the inhibition of inflammation. For example, aged garlic extract (AGE) has been shown to enhance the phosphorylation of Thr172 of the α-subunit of AMPK in several tissues of disease model animals. In addition, AGE has been reported to suppress the progression of atherosclerotic plaque formation in an animal model of atherosclerosis. Moreover, AGE has been found to decrease the level of plasma glycated albumin and to improve hyperglycemia in an animal model of type 2 diabetes. These inhibitory effects of AGE are induced by the suppression of the inflammatory response. In the present review, we discuss the mechanisms through which AGE activates AMPK, as well as the mechanisms through which the activation of AMPK by AGE modulates the inflammatory response in disease models.

Antimicrobial properties of hydrophobic compounds in garlic: Allicin, vinyldithiin, ajoene and diallyl polysulfides.

Allium plants, such as garlic, onion and leek have long been known to be effective in the therapy of infectious diseases. In particular, garlic has a greater antimicrobial activity than other Allium plants as it contains several hydrophobic antimicrobial compounds, such as allicin, vinyldithiins, ajoenes and diallyl polysulfides. Allicin is a characteristic sulfur-containing compound found in raw garlic produced from alliin and exhibits antimicrobial activity against both Gram-positive and Gram-negative bacteria. In addition, allicin has been reported to inhibit the biofilm formation of bacteria, which is a major cause of bacterial resistance to the antibiotic treatment of infections, by regulating quorum sensing in microorganisms. Other hydrophobic compounds also have similar inhibitory effects on bacteria as allicin. These biological properties of garlic-derived hydrophobic compounds can be used to enhance the effects of existing drugs and may thus be used in the treatment of infections, such as by preventing drug resistance through the inhibition of biofilm formation. In this review, we summarize the effects of hydrophobic compounds of garlic on bacteria.

Regulation of immune response by S-1-propenylcysteine through autophagy-mediated protein degradation.

Autophagy is a key event in cellular recycling processes due to its involvement in the intracellular degradation of proteins. It has been demonstrated that S-1-propenylcysteine (S1PC), a characteristic sulfur compound in aged garlic extract, induces the activation of autophagy. S1PC degrades the adaptor protein myeloid differentiation response protein 88 (MyD88) of downstream of Toll-like receptor (TLR) by activating autophagy in vitro and in vivo. The degradation of MyD88 inhibits the TLR signaling pathway, including the phosphorylation of interleukin 1 receptor associated kinase 4 (IRAK4) and nuclear factor (NF)-κB p65 in vitro, and eventually leads to the inhibition of interleukin (IL)-6 production in vitro and C-C motif chemokine ligand 2 (Ccl2) mRNA expression in vivo. S1PC also increases the level of intestinal immunoglobulin A (IgA) and the number of IgA-producing cells in Peyer's patches in vivo. In addition, S1PC triggers the mRNA expression of X-box binding protein 1 (Xbp1), an inducer of IgA-producing cell differentiation via the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and the degradation of paired box protein 5 (Pax5), a suppressor of Xbp1 mRNA expression. The present review summarizes the mechanisms through which the activation of autophagy by S1PC modulates the immune response.

GGC Repeat Expansion of NOTCH2NLC in Adult Patients with Leukoencephalopathy.

Leukoencephalopathies comprise a broad spectrum of disorders, but the genetic background of adult leukoencephalopathies has rarely been assessed. In this study, we analyzed 101 Japanese patients with genetically unresolved adult leukoencephalopathy using whole-exome sequencing and repeat-primed polymerase chain reaction for detecting GGC expansion in NOTCH2NLC. NOTCH2NLC was recently identified as the cause of neuronal intranuclear inclusion disease. We found 12 patients with GGC expansion in NOTCH2NLC as the most frequent cause of adult leukoencephalopathy followed by NOTCH3 variants in our cohort. Furthermore, we found 1 case with de novo GGC expansion, which might explain the underlying pathogenesis of sporadic cases. ANN NEUROL 2019;86:962-968.

Ten-Year Evaluation of the TOYOTA Prehospital Stroke Scale for Tissue Plasminogen Activator Intravenous Therapy in the Real World.

BACKGROUND: Emergency medical services are an important part of acute stroke management. We devised a prehospital stroke scale, the TOYOTA prehospital stroke scale for tissue plasminogen activator (t-PA) intravenous therapy (TOPSPIN) for triaging patients with ischemic stroke and especial indications for intravenous t-PA therapy in December 2006; this scale comprises 5 items including consciousness, atrial fibrillation, language disorder, disturbance of the upper extremities, and disturbance of the lower extremities. The aim of this study was to analyze the results of 10 years of TOPSPIN implementation and to distinguish ischemic stroke from hemorrhagic stroke in the real world. METHODS: We prospectively enrolled consecutive patients who were transferred to our hospital and evaluated by Toyota city ambulance services using the TOPSPIN from December 2006 to January 2017. We examined definite diagnosis at the time of hospital discharge (ischemic stroke, hemorrhagic stroke, or stroke mimic), positive-predictive value of the stroke, the rate of the recanalization therapy, and clinical differentiation among patients with hemorrhagic stroke, ischemic stroke, and stroke mimics. RESULTS: A total of 1,482 consecutive patients were enrolled; 1,134 (76.5%) were patients with stroke (628 ischemic-type, 34 transient ischemic attack-type, and 472 hemorrhagic-type) and 348 (23.5%) without stroke (80 with seizure, 42 with syncope, 27 with hypoglycemia, and 199 other). Among 628 patients with ischemic stroke, 130 (20.7%) received intravenous recombinant t-PA treatment, endovascular therapy, or both. The presence of atrial fibrillation, older age, lower blood pressure, and lower total TOPSPIN score was more commonly associated with ischemic stroke than with hemorrhagic stroke. In multivariable logistic regression analysis, the presence of atrial fibrillation was independently associated with ischemic stroke (OR 2.33; 95% CI 1.61-3.40). CONCLUSIONS: The TOPSPIN is a simple prehospital stroke scale that includes an assessment of atrial fibrillation. Detection of atrial fibrillation in the prehospital stage may point to a higher probability of ischemic stroke.

Anti-inflammatory action of cysteine derivative S-1-propenylcysteine by inducing MyD88 degradation.

The degradation of target proteins by small molecules utilizing the cellular proteolytic system is featured as a treatment strategy of several diseases. We found that S-1-propenylcysteine (S1PC) among several cysteine derivatives in aged garlic extract inhibited TLR-mediated IL-6 production by inducing the degradation of adaptor protein MyD88. We showed that S1PC directly denatured MyD88 and induced the formation of protein aggregates. Consequently, MyD88 was degraded by aggresome-autophagy pathway. On the other hand, S-allylcysteine, a structural analog of S1PC, failed to induce the degradation of MyD88 because of its inability to denature MyD88 although it also activated autophagy. Our findings suggest that S1PC induces MyD88 degradation through the denaturation of MyD88 and the activation of autophagy. Thus, S1PC may serve as the base to develop a therapeutic means for immune diseases associated with aberrant TLR signaling pathways.

[A pedigree of hereditary hyperekplexia].

A 31-year old women presented with excessive startle reflex and frequent falls. Her startle reflex is induced by slight stimuli which are not problematic in most people. Soon after her startle reflex is evoked, generalized muscle stiffness occurs. She becomes rigid and falls down without loss of consciousness. Because she cannot protect herself when she is startled and falls, she has repeatedly bruised her head and face. The pedigree includes her father and two sisters with similar symptoms. Gene analysis revealed GLRA1 mutation, and she was diagnosed with hereditary hyperekplexia (HPX). Symptoms improved with clonazepam 1 mg/day. HPX patients live with severe anxiety about frequent falls and sometimes suffer serious injury, such as cerebral concussion or bone fracture. Although HPX might sometimes be underestimated, accurate diagnosis is very important for effective treatment.

Aged garlic extract suppresses inflammation in apolipoprotein E-knockout mice.

SCOPE: Chronic inflammation plays a major role in the formation and progression of atherosclerotic plaques. To clarify the mode of action of aged garlic extract (AGE) to retard atherosclerosis, we investigated whether AGE suppresses the inflammation in apolipoprotein E-knockout (ApoE-KO) mice. METHODS AND RESULTS: ApoE-KO mice were fed standard diet with or without 3% AGE for 12 wk. AGE feeding inhibited the progression of atherosclerotic lesion by 27% and reduced the level of C-reactive protein (CRP) and thromboxane B2 (TXB2 ), a marker of platelet activation, in serum by 39 and 33%, respectively, compared to ApoE-KO mice without AGE treatment. AGE treatment also decreased the level of tumor necrosis factor alpha (TNF-α), a major stimulus inducing CRP production, in the liver by 35%. AGE decreased the level of interleukin-1 receptor-associated kinase 4 (IRAK4) by 60% and almost doubled the level of phospho-AMP-activated protein kinase (p-AMPK) in the liver. CONCLUSION: The anti-atherosclerotic effect of AGE involves the suppression of inflammation by reducing the serum level of CRP and TXB2 , and the protein level of TNF-α and IRAK4, and increasing AMPK activity in liver.

Familial Pernicious Chronic Intestinal Pseudo-obstruction with a Mitochondrial DNA A3243G Mutation.

We report the case of a mother and two children who shared a mitochondrial DNA A3243G mutation. The mother had diabetes mellitus, neurogenic bladder, bradykinesia, dystonia, and slowly progressive cerebellar ataxia. Her two daughters were diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes at adolescence. They all presented with gastrointestinal symptoms at an advanced clinical stage. They were diagnosed with chronic intestinal pseudo-obstruction, and they were resistant to therapy. The mother and her youngest daughter died from aspiration pneumonia because of vomiting. The determination of chronic intestinal pseudo-obstruction is an important prognostic factor in patients with the mitochondrial DNA A3243G variant.

Chemical and Biological Properties of S-1-Propenyl-l-Cysteine in Aged Garlic Extract.

S-1-Propenyl-l-cysteine (S1PC) is a stereoisomer of S-1-Propenyl-l-cysteine (SAC), an important sulfur-containing amino acid that plays a role for the beneficial pharmacological effects of aged garlic extract (AGE). The existence of S1PC in garlic preparations has been known since the 1960's. However, there was no report regarding the biological and/or pharmacological activity of S1PC until 2016. Recently, we performed a series of studies to examine the chemical, biological, pharmacological and pharmacokinetic properties of S1PC, and obtained some interesting results. S1PC existed only in trace amounts in raw garlic, but its concentration increased almost up to the level similar of SAC through aging process of AGE. S1PC showed immunomodulatory effects in vitro and in vivo, and reduced blood pressure in a hypertensive animal model. A pharmacokinetic study revealed that S1PC was readily absorbed after oral administration in rats and dogs with bioavailability of 88-100%. Additionally, S1PC had little inhibitory influence on human cytochrome P450 activities, even at a concentration of 1 mM. Based on these findings, S1PC was suggested to be another important, pharmacologically active and safe component of AGE similar to SAC. In this review, we highlight some results from recent studies on S1PC and discuss the potential medicinal value of S1PC.