Granzyme B as a novel factor involved in cardiovascular diseases

SummaryApoptosis plays an important role in cardiovascular diseases such as atherosclerosis, ischemic heart disease, and congestive heart failure. Previous studies have demonstrated that oxidative stress, physiological stress, and inflammatory cytokines such as tumor necrosis factor and Fas ligand are involved in apoptosis of cardiovascular system. We demonstrate that another apoptosis-related pathway, i.e. granzyme B/perforin system is involved in cardiovascular diseases. Expression of granzyme B, a member of serine protease family is increased in acute coronary syndrome, coronary artery disease with end-stage renal disease, and subacute stage of acute myocardial infarction. Although granzyme B is extensively researched in immunological disorders, the role of granzyme B/perforin system was not clear in the cardiovascular field. In addition, little is known regarding the inhibition of granzyme B system in the clinical situation. In this review we demonstrate recent findings of granzyme B in cardiovascular diseases and possible therapeutic applications of inhibiting the granzyme B/perforin system

Cellular and molecular aspects of drug transport in the kidney

Cellular and molecular aspects of drug transport in the kidney. The kidney plays an important role in the elimination of numerous hydrophilic xenobiotics, including drugs, toxins, and endogenous compounds. It has developed high-capacity transport systems to prevent urinary loss of filtered nutrients, as well as electrolytes, and simultaneously to facilitate tubular secretion of a wide range of organic ions. Transport systems for organic anions and cations are primarily involved in the secretion of drugs in renal tubules. The identification and characterization of organic anion and cation transporters have been progressing at the molecular level. To date, many members of the organic anion transporter (OAT), organic cation transporter (OCT), and organic anion-transporting polypeptide (oatp) gene families have been found to mediate the transport of diverse organic anions and cations. It has also been suggested that ATP-dependent primary active transporters such as MDR1/P-glycoprotein and the multidrug resistance-associated protein (MRP) gene family function as efflux pumps of renal tubular cells for more hydrophobic molecules and anionic conjugates. Tubular reabsorption of peptide-like drugs such as β-lactam antibiotics across the brush-border membranes appears to be mediated by two distinct H+/peptide cotransporters: PEPT1 and PEPT2. Renal disposition of drugs is the consequence of interaction and/or transport via these diverse secretory and absorptive transporters in renal tubules. Studies of the functional characteristics, such as substrate specificity and transport mechanisms, and of the localization of cloned drug transporters could provide information regarding the cellular network involved in renal handling of drugs. Detailed information concerning molecular and cellular aspects of drug transporters expressed in the kidney has facilitated studies of the mechanisms underlying renal disposition as well as transporter-mediated drug interactions

Sarcoidosis-associated hepatocellular carcinoma

Sarcoidosis is a systemic granulomatous inflammation of unknown etiology, and seems to involve the liver parenchyma in most cases. However, sarcoidosis-associated hepatocellular carcinoma is rare. We report here a case in which a hepatocellular carcinoma occurred within the liver, which was probably involved as a result of systemic sarcoidosis. A 57-year-old Japanese man had been followed up for 2 years because of diabetic nephropathy and sarcoidosis. On admission for pneumonia, imaging studies revealed an unexpected hepatic tumor. Histology revealed a hepatocellular carcinoma accompanied by T-lymphocytic infiltration and marked granulomatous inflammation, which was surrounding some tumor nodules. The background liver parenchyma exhibited a moderate degree of fibrosis with granulomatous inflammation. The patient had no other apparent liver disease such as viral hepatitis, steatohepatitis, or primary biliary cirrhosis. Therefore, in the present case, sarcoidosis may be considered the probable background etiology for hepatocarcinogenesis

Management of deep neck infection by a transnasal approach: a case report

<p>Abstract</p> <p>Introduction</p> <p>Deep neck infection is a life-threatening condition, and intravenous antibiotic therapy is preferable in the early stages of the disease. However, in the advanced stages, surgical drainage should be performed. Although several surgical treatment strategies are available, it is necessary to standardize treatment according to the patient's general condition and history.</p> <p>Case presentation</p> <p>We report the case of a 68-year-old man with a deep neck abscess and with severe diabetes mellitus and inflammation. Computed tomography identified a deep neck infection extending from the level of the epipharynx to that of the hyoid bone. We performed surgical drainage by transnasal endoscopy. The patient exhibited no evidence of either recurrent disease or post-surgical complications within 30 months of follow-up.</p> <p>Conclusions</p> <p>This case report provides evidence that transnasal endoscopic drainage should be recommended as a standard approach in patients with a deep neck abscess and with a severe general condition, diabetes mellitus, and inflammation.</p

A protocol to construct RNA-protein devices for photochemical translational regulation of synthetic mRNAs in mammalian cells

Here, we describe a protocol for the translational regulation of transfected messenger RNAs (mRNAs) using light in mammalian cells. We detail the steps for photocaged ligand synthesis, template DNA preparation, and mRNA synthesis. We describe steps for mRNA transfection, treatment of cells with a photocaged ligand followed by light irradiation, and analysis of the transgene expression. The protocol enables spatiotemporally regulated transgene expression without the risk of insertional mutagenesis

Gender difference in the relationships between vision and hearing impairments and negative well-being.

OBJECTIVES: To evaluate the association of hearing impairment, vision impairment and their combination (dual sensory impairment) with negative well-being such as depression, subjective poor health and the reduced functional ability in community-dwelling older adults, and to determine whether any association varies by gender. METHODS: Between 2005 and 2006, we objectively examined vision and hearing impairment (using best-corrected visual acuity and pure-tone audiometric test) in 843 people aged 65 years and older (351 males, 492 females) in a rural Japanese town. Through a home visit interview survey using a structured questionnaire, we also collected information on depression (the five-item Geriatric Depression Scale), subjective poor health, and reduced functional activity (the Tokyo Metropolitan Institute of Gerontology's Index of Competence). RESULTS: We observed gender differences in the association between sensory impairment and depression. Multiple logistic regression analysis revealed that hearing impairment in males (adjusted odds ratio: 2.22, 95% confidence interval; 1.07-4.61) and vision impairment in females (1.91, 1.14-3.21) were related to depression. Vision impairment and dual sensory impairment were also associated with subjective poor health and reduced functional activity in both sexes. CONCLUSIONS: Sensory impairment is significantly associated with negative well-being in older persons, and its association with depression may differ between males and females

Serum levels of retinol and other antioxidants for hearing impairment among Japanese older adults.

BACKGROUND: The objective of this study was to assess the relation between serum levels of retinol and other antioxidants and hearing impairment in Japanese older adults. METHODS: This is a community-based cross-sectional study comprising 762 residents aged 65 years or older in Kurabuchi, Gumma, Japan. We measured serum retinol and other antioxidants (alpha- and gamma-tocopherols, and carotenoids including beta-cryptoxanthin, alpha- and beta-carotenes, lycopene, and lutein plus zeaxanthin) by high-performance liquid chromatography and divided each measurement into quartiles. Hearing impairment was defined as a failure to hear a 30-dB hearing level (HL) signal at 1 kHz and a 40-dB HL signal at 4 kHz in the better ear in pure-tone audiometric tests. The odds ratios (OR) for hearing impairment were calculated for each of the upper three quartiles of retinol and other antioxidant levels relative to the lowest quartile. RESULTS: Crude analysis showed that serum levels of retinol and provitamin A carotenoids (beta-cryptoxanthin, and alpha- and beta-carotenes) were inversely related to the prevalence of hearing impairment. The multiadjusted ORs (95% confidence intervals) for the highest quartile of retinol and the provitamin A family (combinations of provitamin A carotenoids) compared with the lowest were 0.51 (0.26-1.00) and 0.53 (0.27-1.02), respectively. A dose-response relationship was observed for retinol (p = .03) and provitamin A (p = .09). CONCLUSION: Increased serum levels of retinol and provitamin A carotenoids were clearly associated with a decreased prevalence of hearing impairment