Oral dryness is common among aging individuals and its objective evaluation is an important issue for improving their oral health. In the present study, we measured the objective mucosal moisture in elderly individuals with a moisture checker and evaluated its relation with laboratory findings and subjective oral status. The subjects were 502 adults (244 men and 258 women), with a mean age of 72.3 ± 6.7 years, who participated in a regular medical screening program in Nagasaki Prefecture, Japan. We evaluated the moisture of the oral mucosa by measuring the weight percentage of water content in the oral epithelium, subjective oral dryness, self-assessed chewing ability [“good” (“able to chew all foods”) or “poor” (“able to chew soft foods only” and “unable to chew any foods”)], and laboratory findings. The values obtained with a moisture checker, which represent objective oral mucosal moisture, were significantly lower in women with poor chewing ability than those with good chewing ability (28.2 ± 2.4% vs. 29.2 ± 2.0%, p = 0.004) and in all subjects (28.4 ± 2.4% vs. 29.1 ± 2.0%, p = 0.004), but not in men (28.6 ± 2.5% vs. 29.0 ± 2.0%, p = 0.27). When multiple logistic regression analysis was performed on confounding factors, older age (OR: 1.24, p = 0.015), women (OR: 1.70, p = 0.016), and anemia (OR: 1.96, p = 0.030) were significantly associated with self-assessed chewing ability. Our current study indicates that poor chewing ability is associated with lower mucosal moisture in elderly individuals.
Tobacco smoke-related products and ethanol would induce oxidative modifications to the DNA bases, thereby contributing to larynx cancer. Human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) deals with oxidative DNA damage, and the base changes in the hOGG1 gene may alter the susceptibility of the human cells to tobacco smoke-related compounds and/or ethanol. In the present work, we investigated the association between smoking, drinking or the Ser326Cys polymorphism of the hOGG1 gene and the risk of larynx cancer in a Polish population. It has been reported that the Ser326 allele exhibits higher activity than the Cys326 variant. In this study, 253 age-matched controls and 253 patients with larynx cancer were enrolled. The polymorphism was determined with DNA from blood lymphocytes by polymerase chain reaction. The frequencies (%) of the genotypes were Ser/Ser 65.6, Ser/Cys 30.4, and Cys/Cys 4.0 in the controls and those in patients were 55.7, 36.0 and 8.3, respectively. Stratification of individuals according to their smoking and drinking habits indicated that these habits might be significant risk factors in larynx cancer. The Ser/Cys and Cys/Cys genotypes are significantly associated with the increased risk of larynx cancer. These genotypes increased the risk ratio of larynx cancer among heavy smokers, but did not change the risk in former smokers and moderate smokers. These genotypes also increased the risk of larynx cancer in moderate and heavy drinkers. Therefore, the Cys326 allele of the hOGG1 gene may increase the risk of larynx cancer associated with smoking or alcohol consumption.
Uterine cervical cancer is a leading cause of cancer-related death in the female population worldwide. In vitro chemosensitivity test is important to find effective drugs in uterine cervical cancer that requires the established chemotherapeutic strategies. The purpose of this study is to investigate the chemosensitivity of uterine cervical cancer using the histoculture drug response assay (HDRA). Sixty-five fresh tumor tissues were obtained from patients with cervical cancer: 47 squamous cell carcinomas, 11 adenocarcinomas, and 7 adenosquamous cell carcinomas. The median age was 44 years (range, 25-74 years), and the median follow-up duration was 26.3 months (range, 1.6-52.7 months). The clinical stage by the International Federation of Gynecologists and Obstetricians (FIGO) was stage I of 80.0% (52/65) and stage IIA of 13.8% (9/65). The inhibition rates of ten chemotherapeutic agents against these cancer tissues were tested using the HDRA method according to established methods. Five agents were evaluated as sensitive drugs in cervical cancer with inhibition rates of greater than 30%: 41.0% for carboplatin, 35.0% for cisplatin, 33.8% for paclitaxel, 41.4% for belotecan, and 49.2% for topotecan. Especially, carboplatin combined with paclitaxel showed an inhibition rate of 54.0%, which was higher than any other single agent. However, there were no noticeable differences in chemosensitivity according to histopathologic types and FIGO stage. Despite such limitation, the HDRA may be a promising chemosensitivity test to predict an effective drug for each patient. The HDRA could provide useful information that is invaluable for the design of individualized treatments in patients with cervical cancer.
Urotensin II (UII) is a vasoactive peptide with many potent effects in the cardiorenovascular system and may be involved in the pathogenesis of atherosclerosis. Cardiovascular risk factors are often accompanied by reduced numbers of endothelial progenitor cells (EPCs) and their impaired migratory capacity. However, the role of UII in the migration of EPCs has not been reported so far. The aim of this study was to investigate whether UII influences the chemotactic function of bone marrow-derived EPCs and the possible signaling mechanisms involved. As a ligand for the orphan G-protein coupled receptor 14 (GPR14, UT receptor), UII exerts vasoactive functions through activation of the RhoA/Rho kinase pathway. We therefore analyzed the expression of GPR14 mRNA and protein, the activation of RhoA kinase and the phosphorylation of myosin light chain (MLC) in EPCs, isolated from the rat bone marrow. EPCs of 1-4 passages expressed GPR14 mRNA and protein. Chemotaxis assays were performed using Transwell cell-culture chambers with UII (10-10-10-6 M), showing that UII induced chemotaxis of EPCs in a concentration-dependent manner after 3-h treatment (all p < 0.05), with the highest value (about 3-fold increase) at 10-8 M. UII caused rapid activation of RhoA and increased phosphorylation of MLC. Conversely, a Rho-kinase inhibitor Y-27632 prevented the UII-induced migration and the phosphorylation of MLC. In conclusion, GPR14/UT receptor is expressed in EPCs, and UII induces migration of EPCs via activation of the RhoA/Rho kinase pathway. These findings provide new insights into the actions of UII in atherosclerosis.
Total abdominal hysterectomy (TAH) is most commonly performed for benign lesions and malignant diseases of the uterus. Postoperative immuno-suppression caused by TAH has become a serious clinical problem, due to the high incidence of infectious complications after this operation. Lornoxicam (LOR) is a member of non-steroidal anti-inflammatory drugs and a cyclooxygenase inhibitor. In this study, 45 patients undergoing TAH for uterine myoma were enrolled and given intravenous injection of normal saline (untreated patients) or LOR (8 or 16 mg) preoperatively (15 patients/group). We studied the effects of LOR on postoperative immuno-suppression by determining the serum levels of three cytokines, RANTES, monocyte chemotactic protein-1 (MCP-1), and stromal cell-derived factor 1α (SDF-1α). MCP-1 and RANTES are involved in the pathophysiology of acute and chronic inflammatory processes, and SDF-1α is considered as an inflammatory chemoattractant. Following TAH, the serum levels of RANTES were reduced in the untreated patients, but were significantly higher in the patients treated with LOR. In addition, the levels of MCP-1 and SDF-1α were significantly elevated in the untreated patients, but were significantly lower in the patients treated with LOR. Furthermore, preoperative treatment with LOR 16 mg could regulate the serum levels of these three chemokines more effectively, compared to that with LOR 8 mg. In conclusion, preoperatively intravenous injection of LOR may effectively restrain the decreased serum levels of RANTES and the increased expression of MCP-1 and SDF-1α in TAH patients. LOR may help to maintain the stability of immune function of TAH patients.
Spinal cord injury (SCI) occurs frequently and is a leading cause of permanent disability in young adults. Many immune inhibitors including tacrolimus (FK506) are shown to be helpful in the regeneration of neural tissue following spinal cord injury. FTY720 belongs to a new class of immunosuppressants. The combination of FTY720 and tacrolimus has been reported to elicit synergistic immunosuppresive effects in rat allograft models without causing critical adverse effects. This study was to determine whether the combination of FTY720 and tacrolimus is superior to FTY720 or tacrolimus alone in the treatment of SCI. Forty-eight rats were subjected to a weight-drop contusion at the tenth thoracic level (a 10-g rod dropped from a height of 25 mm). At 30 min after the operation, they were randomly divided into four groups and received treatment with either FTY720 (0.5 mg/kg), tacrolimus (0.5 mg/kg), FTY720 + tacrolimus (0.5 mg/kg and 0.5 mg/kg respectively) or saline via gavage. Functional recovery was evaluated during 42 days after SCI via open-field test, inclined plane test, footprint analysis, somatosensory evoked potentials (SSEPs), and electron microscopic analysis. Rats from three treatment groups showed significantly better locomotor functional outcomes, higher SSEP amplitude, shorter SSEP latency, and milder pathological changes compared with those of control group. Moreover, rats treated with a combination of FTY720 and tacrolimus demonstrated significantly greater functional recovery by day 14 after SCI than those treated with either FTY720 or tacrolimus alone. These results suggest that the combination of FTY720 and tacrolimus could be a potentially effective therapeutic strategy to treat SCI.
Seasonal variation in the occurrence of atrial fibrillation (AF) has been documented, yet precise mechanisms and factors underlying the phenomenon remain unclear. We have previously observed the decrease in the number of AF paroxysms between May and August, when sunshine levels were highest. The objective of the present study was, in turn, to determine whether sunshine affects the incidence of AF episodes. Participants were 1,475 Caucasian subjects (mean age: 68.2 years) diagnosed with AF paroxysms, admitted to the Intensive Cardiac Care Unit (ICCU) between January 1, 2005 and December 31, 2008; 805 were women and 670 were men (mean age: 69.2 and 66.2, respectively). The average incidence of AF episodes was higher among female subjects, with 16.8 cases per month, compared to male subjects with 14.0 cases per month. Pearson's correlation coefficient (r) was used to find a relationship between monthly sums of sunshine duration and AF paroxysms. This relationship for women was clearly inversely proportional (r = −0.499); namely, most AF episodes were recorded from December to March, when sunshine levels were lowest. In contrast, there was no noticeable association in male patients between the occurrence of AF paroxysms and effective sunshine (r = −0.126). In conclusion, unlike in men, a marked, statistically confirmed relationship between AF episodes and effective sunshine was observed in women. Thus, sunshine may have a protective effect against AF paroxysms for women. Our findings may provide the basic information concerning the influence of environmental factors on human wellbeing and contribute to management of AF.
Tanis, a newly discovered membrane protein, has been suggested to be involved in the development of insulin resistance (IR). In addition, Tanis was postulated as a hepatic receptor for an inflammatory marker, serum amyloid A-1 (SAA1), which represents a risk factor for cardiovascular disease. The aim of this study was to investigate the potential role of Tanis and SAA1 in the development of IR using a rat model. Male Sprague-Dawley (6 weeks old) rats were divided into three groups (n = 10 for each group): control, IR, and rosiglitazone-treated IR. Rosiglitazone is an insulin sensitizer that is used for treatment of type 2 diabetes. Rats were fed a high-fat diet for 35 days to induce IR, as judged by increased plasma glucose and insulin concentrations, following an oral glucose tolerance test. Rats of three groups were sacrificed, and the livers were dissected for RNA preparation. Real-time PCR analysis revealed that Tanis and SAA1 mRNA levels were significantly higher in the livers of IR rats than those of control rats fed a standard diet and those of IR rats treated for 35 days with rosiglitazone. Importantly, there was no significant difference in Tanis and SAA1 mRNA levels between control and rosiglitazone-treated IR rats. Furthermore, the expression levels of Tanis mRNA are positively correlated with those of SAA1 mRNA in the livers of control, IR and rosiglitazone-treated IR rats. In conclusion, high expression of Tanis mRNA in the liver is associated with the development of IR probably via the function of SAA1.
Adipocyte differentiation is an important aspect in energy homeostasis. Although the regulation of adipocyte differentiation is relatively well understood, the underlying molecular mechanism remains unclear. In this study, subcutaneous and epididymal adipose tissues were used to study the differential expression of associated genes. We found that the expression level of mouse homologue of rat prostatic androgen-repressed message-1 (mPARM-1) gene was higher in subcutaneous, perirenal and mesenteric adipose tissues than in epididymal adipose tissue. In mouse subcutaneous, perirenal, and mesenteric adipose tissues, the expression level of this gene was higher in adipocytes than in non-adipocyte cells, i.e. stromal-vascular cells. Furthermore, mPARM-1 mRNA expression was up-regulated in subcutaneous, mesenteric, and epididymal adipose tissues of mice fed a high-fat diet compared to those fed a normal-fat diet. Expression level of mPARM-1 mRNA increased in the early stage of the chemically induced adipocyte differentiation, preceding the increase in peroxisome proliferator-activated receptor-gamma 2 (PPAR-γ2) mRNA. Tumor necrosis factor-alpha (TNF-α), an inhibitor of adipocyte differentiation, reduced the expression of mPARM-1 mRNA in differentiated 3T3-L1 cells and subsequently down-regulated the expression of adipogenic genes, including PPAR-γ2, leptin and adipogenin. Moreover, knockdown of mPARM-1 expression with siRNA reduced lipid accumulation and the expression levels of PPAR-γ2 and adipocyte protein 2 mRNAs, which suggest that the degree of adipocyte differentiation of 3T3-L1 cells has been reduced. These results indicate that mPARM-1 might be involved in the regulation of fat accumulation and adipocyte differentiation.
Daikenchuto is a traditional herbal medicine that is used for the treatment of cold feeling in the abdomen, while Orengedokuto, also a traditional herbal medicine, is used for treating inflammatory and ulcerative diseases affecting internal organs. However, the effects of these herbal medicines on cardiac output (CO) and intestinal blood flow have never been investigated. This examiner-blinded randomized crossover study intended to clarify the influence of Daikenchuto and Orengedokuto on CO and blood flow volume in the superior mesenteric artery (SMA). Fourteen healthy men (35 ± 7 years old) were randomly assigned to two groups: group A and group B. Initially, all subjects were given 50 ml of water orally. After 7 days, subjects in group A were given 5.0 g of Daikenchuto, and 7 days later they were given 2.5 g of Orengedokuto. These herbal medicines were given to group B subjects in the reverse order. CO and SMA blood flow volume were measured from rest to 90 min after the administration of water or each medicine. There was a significant increase in SMA blood flow volume after the administration of Daikenchuto, compared to water alone (p < 0.05) and Orengedokuto (p < 0.05). SMA blood flow volume was significantly increased between 5 and 90 min after administration of Daikenchuto (p < 0.01) compared to the resting state. However, there was no significant change in CO after the administration of either agent. The present study indicates that Daikenchuto increases SMA blood flow volume without increasing CO.
Essential hypertension is a disease of unknown pathogenesis, although renal function has been implicated as an important factor in its cause. Stroke-prone spontaneously hypertensive (SHRSP) rats provide an animal model of essential hypertension. To understand the cause of hypertension, identifying proteins that are differentially expressed between hypertensive and normotensive rats may provide a key. Here, proteins in the renal cortex from SHRSP rats, malignant stroke-prone spontaneously hypertensive (M-SHRSP) rats, and Wistar Kyoto (WKY) rats as a normotensive control were subjected to two-dimensional difference gel electrophoresis (2D-DIGE). After in-gel digestion by trypsin, proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). Several proteins showed differential expression patterns between hypertensive and normotensive rats. Among them, we focused on catechol-O-methyltransferase (COMT) because this enzyme inactivates catecholamines, possibly affecting blood pressure. To confirm the differential expression of COMT in each animal, we conducted Western blot analysis, which revealed that the expression of COMT is lower in M-SHRSP rats than in control and SHRSP rats, indicating that blood pressure and expression of COMT are related. In fact, the blood pressure of M-SHRSP rats was significantly higher than that of SHRSP rats at age of 10 weeks. Immunohistochemical and immunofluorescence studies showed that COMT in renal cortex is localized in tubular epithelial cells. The expression of COMT is lower in the renal cortex tubular epithelium of M-SHRSP rats than in normotensive rats. These results suggest that the decreased expression of COMT may be an important factor leading to the development of hypertension.
The uncoupling protein-1 (UCP1) gene is of major importance for regulation of body weight and lipid/lipoprotein metabolism. Our cross-sectional study has shown that subjects with the G/G genotype of the -3826 A/G polymorphism in the UCP-1 gene have higher levels of serum high-density lipoprotein cholesterol (HDL-C) than those with other genotypes. Low circulating HDL-C level has been regarded as a major atherosclerotic risk factor. We therefore investigated whether the -3826 A/G polymorphism affects the obesity- and lipid-related parameters during a low-calorie diet (LCD) intervention. In 32 obese women (49.9 ± 8.4 years of age), anthropometric, physiological and biochemical characteristics were measured before and after a 2-month LCD treatment, which restricted each subject to the same energy intakes, such as 5,120 kJ/day. The -3826 A/G polymorphism was detected using a PCR-restriction fragment-length polymorphism method. There were 6 subjects with the A/A genotype, 15 with the A/G genotype and 11 with the G/G genotype. The LCD intervention decreased weight (P < 0.001) and serum HDL-C levels (P < 0.05) in all subjects. There was no difference in the levels of change in weight, nutrient intake, physiological measurements in energy expenditure, and fat oxidation between subjects with and without the G allele. In contrast, the degree of the reduction in the HDL-C levels was significantly smaller in subjects with the G allele than those without the G allele. These results suggest that the G allele at -3826 in the UCP1 gene may ameliorate the reduction in serum HDL-C levels in obese women during LCD.