Improvement of Transdermal Delivery of Tetragastrin by Lipophilic Modification with Fatty Acids

The in-vitro permeability of chemically modified tetragastrin with fatty acids through the rat skin was studied. The permeability of these compounds through intact skin and stripped skin of rat was determined with a Franz-type diffusion cell. The permeation of tetragastrin across the intact skin was improved by chemical modification with acetic acid and butyric acid. However, tetragastrin and caproyl-tetragastrin did not permeate across the intact skin up to the end of experiment. The permeation of tetragastrin across the stripped skin was improved by chemical modification, the skin flux of these acyl derivatives being in the order: acetyl > butyroyl > caproyl. The stability of tetragastrin in skin homogenate was also significantly improved by chemical modification with fatty acids. These results suggest that chemical modification of tetragastrin with fatty acids increases its lipophilicity, which makes it permeable across the stratum corneum. Moreover, the chemical modification reduced the degradation of tetragastrin in the viable skin, resulting an increase in permeation of tetragastrin across the skin.     

GENOTYPES OF ALDH2 RELATED TO LIVER AND PULMONARY DISEASES AND OTHER GENETIC FACTORS RELATED TO ALCOHOLIC LIVER DISEASE

Genetic factors related to the development of alcoholic liverand pancreatic diseases (ALD and APD) and of alcohol-inducedasthma were analyzed. The development of ALD is geneticallycontrolled and is directly associated with the polymorphismsof the genes of acetaldehyde (Ac-CHO) and ethanol-metabolizingenzymes, aldehyde dehydrogenase-2 (ALDH2) and cytochrome P4502E1.The development of ALD and APD may also be genetically linkedwith the induction of gamma-glutamyl transferase (GTT) by alcohol.Alcohol-induced asthma is related to the genotypes of ALDH2and is caused by rapid elevation of blood Ac-CHO. ALDH1 playsa very important role in the oxidation of Ac CHO in blood.     

An Acute Myocardial Infarction Case that Survived An Out‐of‐Hospital Cardiac Arrest in Which Prominent Ischemic J Waves Were Documented

We describe a case of a myocardial infarction, in which prominent ischemic J waves were documented during recurrent ventricular fibrillation attacks. The patient was referred to our hospital to treat an out‐of hospital cardiac arrest. Although the 12‐lead electrocardiogram obtained just after the first cardioversion did not show any apparent J waves, a J wave‐like steep downsloping type ST‐segment elevation associated with q waves in the inferior leads was documented during multiple episodes of ventricular fibrillation. Our report revealed the appearance of J waves as an important marker for lethal arrhythmias in acute ischemia. (PACE 2012; 35:e27–e30)     

The Economic Impact of Loss of Performance Due to Absenteeism and Presenteeism Caused by Depressive Symptoms and Comorbid Health Conditions among Japanese Workers

We aimed to determine the economic impact of absenteeism and presenteeism from five conditions potentially comorbid with depressive symptoms—back or neck disorders, depression, anxiety, or emotional disorders, chronic headaches, stomach or bowel disorders, and insomnia—among Japanese workers aged 18–59 yr. Participants from 19 workplaces anonymously completed Stanford Presenteeism Scale questionnaires. Participants identified one primary health condition and determined the resultant performance loss (0–100%) over the previous 4-wk period. We estimated the wage loss by gender, using 10-yr age bands. A total of 6,777 participants undertook the study. Of these, we extracted the data for those in the 18–59 yr age band who chose targeted primary health conditions (males, 2,535; females 2,465). The primary health condition identified was back or neck disorders. We found that wage loss due to presenteeism and absenteeism per 100 workers across all 10-yr age bands was high for back or neck disorders. Wage loss per person was relatively high among those identifying depression, anxiety, or emotional disorders. These findings offer insight into developing strategies for workplace interventions on increasing work performance.     

Development of a Short Version of the New Brief Job Stress Questionnaire

This study was aimed to investigate the test-retest reliability and validity of a short version of the New Brief Job Stress Questionnaire (New BJSQ) whose scales have one item selected from a standard version. Based on the results from an anonymous web-based questionnaire of occupational health staffs and personnel/labor staffs, we selected higher-priority scales from the standard version. After selecting one item with highest item-total correlation coefficient from each scale, a 23-item questionnaire was developed. A nationally representative survey was administered to Japanese employees (n=1,633) to examine test-retest reliability and validity. Most scales (or items) showed modest but adequate levels of test-retest reliability (r>0.50). Furthermore, job demands and job resources scales (or items) were associated with mental and physical stress reactions while job resources scales (or items) were also associated with positive outcomes. These findings provided a piece of evidence that the short version of the New BJSQ is reliable and valid.     

The Mediating and Moderating Effects of Workplace Social Capital on the Associations between Adverse Work Characteristics and Psychological Distress among Japanese Workers

Our current study investigated how workplace social capital (WSC) mediates and moderates the associations between adverse work characteristics and psychological distress among Japanese workers. We collected cross-sectional data (N=9,350) from a baseline survey of an occupational Japanese cohort study. We focused on individual WSC and considered job demands/control, effort/reward, and two types (i.e., procedural and interactional) of organizational justice as work-characteristic variables. We defined psychological distress as a score of ≥5 on the Kessler Psychological Distress Scale (K6 scale). Multivariate logistic regression analyses predicted a binary variable of psychological distress by individual WSC and adverse work characteristics, adjusting for individual-level covariates. Individual WSC mediated the associations between adverse work characteristics and psychological distress in almost all model specifications. Additionally, individual WSC moderated the associations of psychological distress with high job demands, high effort, and low interactional justice when we used a high WSC cutoff point. In contrast, individual WSC did not moderate such interactions with low job control, reward, or procedural justice. We concluded that individual WSC mediated the associations between adverse work characteristics and psychological distress among Japanese workers while selectively moderating their associations at high levels of WSC.     

Detection of invasive protein profile of Streptococcus pyogenes M1 isolates from pharyngitis patients

Hasegawa T, Okamoto A, Kamimura T, Tatsuno I, Hashikawa S‐N, Yabutani M, Matsumoto M, Yamada K, Isaka M, Minami M, Ohta M. Detection of invasive protein profile of Streptococcus pyogenes M1 isolates from pharyngitis patients. APMIS 2010; 118: 167–78. Streptococcal toxic shock syndrome (STSS) is a re‐emerging infectious disease in Japan and many other developed countries. Epidemiological studies have revealed that the M1 serotype of Streptococcus pyogenes is the most dominant causative isolate of STSS. Recent characterization of M1 isolates revealed that the mutation of covS, one of the two‐component regulatory systems, plays an important role in STSS by altering protein expression. We analyzed the M1 S. pyogenes clinical isolates before or after 1990 in Japan, using two‐dimensional gel electrophoresis (2‐DE) and pulsed‐field gel electrophoresis (PFGE). PFGE profiles were different between the isolates before and after 1990. Markedly different profiles among isolates after 1990 from STSS and pharyngitis patients were detected. Sequence analysis of two‐component regulatory systems showed that covS mutations were detected not only in STSS but also in three pharyngitis isolates, in which proteins from the culture supernatant displayed the invasive type. The mutated CovS detected in the pharyngitis isolates had impaired function on the production of streptococcal pyrogenic exotoxin B (SpeB) analyzed by 2‐DE. These results suggest that several covS mutations that lead to the malfunction of the CovS protein occurred even in pharyngeal infection.     

Identification of two novel mutations in non-Jewish factor XI deficiency

Summary. We have studied two heterozygous unrelated CRM non-Jewish FXI-deficient patients. Neither of the patients carries a previously described mutation. Their FXI genes were screened by SSCP analysis following PCR amplification of each exon and the flanking intronic sequences. DNA fragments showing aberrant mobility were cloned and sequenced. The following mutations were identified: in case 1, a T to G transition in exon 12 results in the substitution of Phe-442 by Val (FXI-F442V); in case 2 a C to A transition in exon 5 results in the substitution of Cys-128 by a nonsense codon (FXI-C128X). The missense mutation results in a substitution within the protease domain of FXI. Molecular modelling locates this residue in a structurally conserved region of the protease domain and the amino acid substitution may therefore interfere with either chain folding and subsequent secretion or the stability of the protein in plasma. We conclude that the mutations which we have identified are responsible for the inherited abnormality in these patients.