The Kidney and Hypertension: Pathogenesis of Salt-Sensitive Hypertension

Salt-sensitive hypertension is closely related with natriuretic capacity of the kidney. Besides several genome-wide research reported candidate gene or gene polymorphism responsible for salt-sensitive hypertension, recently, several new factors for acquired salt-sensitive hypertension are reported. Among them, we have identified that rac1, a small GTPase, activates mineralocorticoid receptor in aldosterone-independent fashion and induces salt-sensitive hypertension in several rodent model. On the other hand, sympathoactivation in the brain and/or kidney regulate sodium handlings in the kidney. Recently it is reported that oxidative stress in the brain or in the kidney may modulate sympathetic tone. Moreover, we reported that β2 adrenoceptor alters histone acetylation and further regulates sodium resorption at distal tubules via activating glucocorticoid receptor. These regulations are to be confirmed in humans and the future, and may open a new door for diagnosis and treatment of salt-sensitive hypertension or moreover preventing development of salt-sensitive hypertension.     

Paraoxonase-1 activity affects the clopidogrel response in CYP2C19 loss-of-function carriers

Background

The impact of paraoxonase-1 (PON1) activity on the response to clopidogrel may differ in patients treated with drug-eluting stents (DES) in association with CYP2C19 loss-of-function (LOF) polymorphisms.

Methods

This study included 112 Japanese patients receiving clopidogrel (75 mg/day) and aspirin (100 mg/day) who underwent optical coherence tomography (OCT) examination 9 months after DES implantation. The CYP2C19 genotype was analyzed and LOF carriers (*1/*2, *1/*3, *2/*2, *3/*3, *2/*3) were identified. At the 9-month follow-up, platelet reactivity was determined by measuring the P2Y12 reactivity unit (PRU) using a VerifyNow P2Y12 assay, PON1 activity was evaluated and intra-stent thrombus was evaluated by OCT.

Results

Of the 112 Japanese patients, 75 were LOF carriers (67.0%). The patients were divided into tertiles according to the PON1 activity (tertile 1; < 230 U/L, tertile 2; 230–283 U/L, tertile 3; > 283 U/L). In the VerifyNowP2Y12 analysis, tertile 1 had a higher PRU than tertiles 2 and 3 in LOF carriers, and there was no difference among tertiles in non-carriers. The highest incidence of intra-stent thrombus was observed in tertile 1 followed by tertiles 2 and 3 in LOF carriers, whereas there was no such difference in non-carriers. Multivariate analysis revealed that LOF carriers and PON1 activity tertile 1 were independent predictors of intra-stent thrombus in all patients. In LOF carriers, tertile 1 was the only independent predictor for intra-stent thrombus.

Conclusion

Low PON1 activity is associated with a low response to clopidogrel and a high frequency of intra-stent thrombus only in LOF carriers.     

Alexander disease with mild dorsal brainstem atrophy and infantile spasms

We present the case of a Japanese male infant with Alexander disease who developed infantile spasms at 8 months of age. The patient had a cluster of partial seizures at 4 months of age. He presented with mild general hypotonia and developmental delay. Macrocephaly was not observed. Brain magnetic resonance imaging (MRI) findings fulfilled all MRI-based criteria for the diagnosis of Alexander disease and revealed mild atrophy of the dorsal pons and medulla oblongata with abnormal intensities. DNA analysis disclosed a novel heterozygous missense mutation (c.1154 C>T, p.S385F) in the glial fibrillary acidic protein gene. At 8 months of age, tonic spasms occurred, and electroencephalography (EEG) revealed hypsarrhythmia. Lamotrigine effectively controlled the infantile spasms and improved the abnormal EEG findings. Although most patients with infantile Alexander disease have epilepsy, infantile spasms are rare. This comorbid condition may be associated with the distribution of the brain lesions and the age at onset of Alexander disease.     

Ultrasound evaluation of fetal brain dysfunction based on behavioral patterns

To identify fetuses at high risk of poor neurological outcomes using a novel ultrasound evaluation system. We assessed an ultrasound evaluation system based on our previous findings, consisting of screening for decreased or lack of fetal movements, abnormal patterns of fetal heart rate, congenital CNS malformations, polyhydramnios of unknown cause, and a “brief ultrasound evaluation” of fetal brain functions, including movement of extremities, breathing movements, ultradian rhythm, REM period, and NREM period. We then assessed the correlation between fetal brain functions and neurological outcomes in infancy (MR, CP, and low Developmental Quotient). During screening, we prospectively evaluated 4978 fetuses receiving prenatal and intrapartum management between January 2000 and December 2009 in our hospital that were later delivered between 32 and 41 weeks’ gestation and identified 93 cases as suspicious for impairment. Of the 93 fetuses, 26 underwent the second step of brief ultrasound examination at 35–40 weeks’ gestation. Our findings revealed that this method was adequately sensitive (80%) and specific (88%) in identifying neurological impairment. We concluded that this method was mainly useful in the clinical setting for establishing the first indication for fetal CNS examination for functional impairment, rendering it suitable for clinical application.     

A new and sensitive method for quantitative determination of helium in human blood by gas chromatography–mass spectrometry using naturally existing neon-21 as internal standard

Forensic Toxicology - In this study, we proposed a new sensitive quantitative method for detecting helium in human blood by gas chromatography–selected-ion monitoring (SIM)-mass spectrometry...     

The interrelationship between an anthropophobic tendency and narcissistic personality in adolescence

This study investigates the interrelationship between an anthropophobic tendency and narcissistic personality in adolescence. Previous research has proposed that anthropophobia and narcissistic personality disorders can be classified into subtypes. In recent studies, Okano (1998) suggested that the relationship between an anthropophobic tendency and narcissistic personality should be explained in terms of two dimensions (two-dimension model), instead of one dimension (one-dimension model). Questionnaires were administered to 305 adolescents who were enrolled in a university. In analysis 1, the relationship between an anthropophobic tendency and narcissistic personality, which are both within normal limits of anthropophobia and narcissism in adolescence, was examined with a two-dimension model. In analysis 2, the characteristics of self-consciousness and adaptiveness in adolescence, which were classified using a two-dimension model, were examined. The results were as follows: (1) an anthropophobic tendency and narcissistic personality could be explained with a two-dimension model; and (2) the characteristics of five subtypes were revealed in detail.     

Asperger syndrome; the issue and the truth

In recent years, Asperger disorder became a key issue in Japan. Serious crimes which have been caused by high-functioning PDD adolescents have become a social problem. Total population study of PDD showed the increase of these children, and the most recent study reported the prevalence to be 2%, in Nagoya City. Now, we have at least one PDD in every school class. It poses a serious problem for Japanese school education. On the other hand, it had gradually become apparent that there are many PDD adult who had been misdiagnosed with other psychiatric disorders; schizophrenia, BPD and so on. The author discusses the relevant issue of Asperger disorder and high-functioning PDD from a clinical perspective.