Metabolic syndrome associates with left atrial dysfunction.

BACKGROUND AND AIMS: Obesity and metabolic syndrome (MetS) are risk factors of atrial fibrillation (AF), but limited data exist on their effect on left atrial (LA) function. The aim of the study was to evaluate the effects of cardiac, hepatic and intra-abdominal ectopic fat depots and cardiometabolic risk factors on LA function in non-diabetic male subjects. METHODS AND RESULTS: Myocardial and hepatic triglyceride contents were measured with 1.5T 1H-magnetic resonance spectroscopy and LA and left ventricular function, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), epicardial and pericardial fat by magnetic resonance imaging (MRI) in 33 men with MetS and 40 men without MetS. LA volumes were assessed using a novel three-chamber orientation based MRI approach. LA ejection fraction (EF) was lower in MetS patients than in the control group (44 ± 7.7% in MetS vs. 49 ± 8.6% in controls, p = 0.013) without LA enlargement, indicating LA dysfunction. LA EF correlated negatively with waist circumference, body mass index, SAT, VAT, fasting serum insulin, and homeostasis model assessment of insulin resistance index, and positively with fasting serum high-density lipoprotein cholesterol. VAT was the best predictor of reduced LA EF. CONCLUSIONS: MetS associates with subclinical LA dysfunction. Multiple components of MetS are related to LA dysfunction, notably visceral obesity and insulin resistance. Further studies are needed to elucidate the role of mechanical atrial remodeling in the development of AF.

Biomarkers and prediction of myocardial triglyceride content in non-diabetic men.

BACKGROUND AND AIMS: Lipid oversupply to cardiomyocytes or decreased utilization of lipids leads to cardiac steatosis. We aimed to examine the role of different circulating metabolic biomarkers as predictors of myocardial triglyceride (TG) content in non-diabetic men. METHODS AND RESULTS: Myocardial and hepatic TG contents were measured with 1.5 T magnetic resonance (MR) spectroscopy, and LV function, visceral adipose tissue (VAT), abdominal subcutaneous tissue (SAT), epicardial and pericardial fat by MR imaging in 76 non-diabetic men. Serum concentration of circulating metabolic biomarkers [adiponectin, leptin, adipocyte-fatty acid binding protein 4 (A-FABP 4), resistin, and lipocalin-2] including ß-hydroxybuturate (ß-OHB) were measured. Subjects were stratified by tertiles of myocardial TG into low, moderate, and high myocardial TG content groups. Concentrations of ß-OHB were lower (p = 0.003) and serum levels of A-FABP 4 were higher (p < 0.001) in the group with high myocardial TG content compared with the group with low myocardial TG content. ß-OHB was negatively correlated with myocardial TG content (r = -0.316, p = 0.006), whereas A-FABP 4 was not correlated with myocardial TG content (r = 0.192, p = 0.103). In multivariable analyses ß-OHB and plasma glucose levels were the best predictors of myocardial TG content independently of VAT and hepatic TG content. The model explained 58.8% of the variance in myocardial TG content. CONCLUSION: Our data showed that ß-OHB and fasting glucose were the best predictors of myocardial TG content in non-diabetic men. These data suggest that hyperglycemia and alterations in lipid oxidation may be associated with cardiac steatosis in humans.

Electrocardiographic changes associated with insulin resistance.

BACKGROUND AND AIM: Cardiac steatosis has been related to increased risk of heart disease. We investigated the association between cardiac steatosis, electrocardiographic (ECG) abnormalities, and individual components of the metabolic syndrome (MetS). METHODS AND RESULTS: A 12-lead ECG and laboratory data were examined in 31 men with the MetS and in 38 men without the MetS. Myocardial triglyceride (MTG) content was measured with 1.5 T magnetic resonance (MR) spectroscopy and epicardial and pericardial fat by MR imaging. MTG content, epicardial and pericardial fat depots were higher in men with the MetS compared with subjects without the MetS (p < 0.001). The heart rate was increased (p < 0.001), the PR interval was longer (p < 0.044), the frontal plane QRS axis shifted to the left (p < 0.001), and the QRS voltage (p < 0.001) was lower in subjects with the MetS. The frontal plane QRS axis and the QRS voltage were inversely correlated with MTG content, waist circumference (WC), body mass index (BMI), TGs, and fasting blood glucose. High-density lipoprotein cholesterol correlated positively and measures of insulin resistance negatively with the QRS voltage. MTG content and hypertriglyceridemia were determinants of the frontal plane QRS and WC and hyperglycemia were predictors of the QRS voltage. CONCLUSION: The MetS and cardiac steatosis appear to associate with multiple changes on 12-lead ECG. The frontal plane QRS axis is shifted to the left and the QRS voltage is lower in subjects with the MetS. Standard ECG criteria may underestimate the presence of left ventricular hypertrophy in obese subjects with cardiometabolic risk factors.

Molecular signaling in muscle is affected by the specificity of resistance exercise protocol.

Mammalian target of rapamycin and mitogen-activated protein kinase (MAPK) signaling pathways have been highlighted as important for muscle adaptations and thus, they may distinguish adaptations to different exercises. Typically, resistance exercise designed for muscle hypertrophy has moderate intensity (60-80% of one repetition maximum, 1 RM) while one prioritizing maximal strength with minor hypertrophy has a higher intensity (≥90% of 1 RM). Eight untrained men (28.4 ± 3.7 years) conducted two different bilateral leg press exercise protocols: hypertrophic (5 × 10 RM) and pure maximal strength (15 × 1 RM) in a counterbalanced, cross-over design with 1 week between exercises. Vastus lateralis muscle biopsies were taken before and 0.5 h after resistance exercise, or in six controls (26.5 ± 3.6 years) who rested. The phosphorylation of p70S6K (Thr(421) /Ser(424) ), rpS6 (Ser(240/244) and Ser(235/236) ) and MAPK p38 as increased (∼2-16 fold) after both exercise protocols. However, the phosphorylation of MAPK Erk1/2 and p70S6K at Thr(389) increased only after 5 × 10 RM. The increase in the phosphorylation of p70S6K (Thr(421) /Ser(424) ), rpS6 (Ser(235/236) ) and Erk1/2 were higher after 5 × 10 RM (P<0.05). No changes were seen in controls. In conclusion, MAPK signaling is greater after hypertrophic than maximal strength exercise protocol. This may mediate adaptations specific to these different types of training regimens.

Load carrying walking test and its relationships to endurance and neuromuscular capabilities in women and men of different ages.

The aim of this study was to examine load carrying walking test (TMload) performance on the treadmill and its associations to endurance and neuromuscular capabilities in women and men of different ages. Sixty participants (aged 28 to 71 years) were divided into young, middle-aged and old groups of both genders. Clinical stress test was performed by stationary cycle ergometer (CEload). Peak oxygen uptake (VO2peak), heart rate and lactate concentration were measured using maximal TMload test. Isometric strength and EMG-activity of upper and lower extremities were measured before and after TMload. VO2peak of TMload correlated significantly with TMload exercise time (ET) in all other groups (r=0.67 to 0.91 and p ≤ 0.05 to p<0.001) except old men. Leg extension force decreased (p ≤ 0.05 to p<0.001) after TMload in all groups, grip force in young groups (p ≤ 0.05), while plantar flexion force and all EMGs remained unchanged. In men VO2peak explained 81% and in women VO2peak and age explained 87% of the total variation of the TMload ET. In conclusion, ET of TMload is associated with high VO2peak, but not with muscle strength or its changes during the loading. The present load carrying walking test may be used for testing workers with heavy loading in their occupation or in rehabilitation purposes. Further research is needed to examine in more detailed the loading model of the present study as well as the effects of different types of training on load carrying performance.

Strength, [corrected] endurance or combined training elicit diverse skeletal muscle myosin heavy chain isoform proportion but unaltered androgen receptor concentration in older men.

We investigated whether the myosin heavy chain (MyHC) proportion and androgen receptor (AR) concentration in skeletal muscle differ following 21 weeks of strength, endurance and combined training in untrained older men. Strength (S) and endurance (E) groups trained twice per week and combined (S+E) group trained four times per week (two strength and two endurance). Muscle biopsies were obtained before and after the training period from m. vastus lateralis (VL) and AR mRNA and protein concentration and MyHC proportion were determined. 1RM increased during the training period in S, S+E and E but the changes were greater in S and S+E than in E. Statistically significant increases were observed only in S and S+E in maximal isometric force as well as in VL thickness. VO (2max) increased significantly only in E. MyHCIIa proportion increased in S, while MyHCIIa proportion decreased and MyHCI increased (p<0.05) in E. No statistically significant changes were observed in serum testosterone and in AR mRNA or protein concentrations. The present results indicate that 21 weeks of strength, endurance or combined training changed MyHC proportion according to the training method but did not have an effect on AR mRNA or protein expression in skeletal muscle at rest.

Effects of morning vs. evening combined strength and endurance training on physical performance, sleep and well-being.

The aim of the present study was to examine how combined strength and endurance training in the morning and evening influences the adaptations in strength and endurance performance, perception of time management, psychological well-being and sleep. The combined training period lasted for 24 weeks and the participants were divided into the morning training (MG, n = 18), evening training (EG, n = 24) and control groups (CG, n = 10). Isometric leg press force (iLP), maximal oxygen consumption (VO2max), sleep behavior, fatigue, time management, motivation, self-esteem and health-related quality of life (HRQoL) were assessed. Morning to evening difference in iLP was observed in both MG and EG at Pre and Post, with higher force values in the evening, but not for VO2max. iLP force increased significantly in EG in the morning (p < 0.001) and evening (p = 0.010). VO2max increased in MG and EG both in the morning (both p < 0.001) and in the evening (MG: p < 0.001; EG: p = 0.003). Participants of the present study slept 7-8 h per night and the self-reported sleep duration, get-up time and the average time to go to bed were similar between the groups and did not change from Pre to Post. From HRQoL dimensions, the score for bodily pain decreased in MG (p = 0.029) and significant between-group differences were observed for Pre-Post changes in MG and EG (p = 0.001) as well as between MG and CG (p < 0.001). In vitality, a significant between-group difference was observed for Pre to Post changes in MG and EG (p = 0.014). Perception of time management decreased in EG (p = 0.042) but stayed unchanged for MG and CG. For the intrinsic motivation to participate, significant between-group differences were observed for MG and EG (p = 0.033) and between MG and CG (p = 0.032) for Pre to Post changes. Self-esteem improved in MG (p = 0.029) and EG (p = 0.024). The present combined strength and endurance training program performed in the morning and in the evening led to similar improvements in strength and endurance performance. Training in the morning or in the evening did not disrupt the already good sleep behavior and it was able to further increase the self-esteem. Although training in the morning hours may leave more time for free time activities or social life (i.e. family and friends) compared to the evening training, it might be more challenging to stay motivated to participate in prolonged training programs in the morning hours.

Effects of prolonged combined strength and endurance training on physical fitness, body composition and serum hormones in women with rheumatoid arthritis and in healthy controls.

OBJECTIVE: The effects of a 21-week combined strength and endurance training period on physical fitness, serum hormone concentrations, and subcutaneous fat in 23 women with rheumatoid arthritis (RA) and in 12 matched healthy subjects was studied. METHODS: The measurements included leg extension forces and EMG activity, muscle and fat thickness on thigh, maximal oxygen uptake (VO2max) and serum concentrations of testosterone, free testosterone, growth hormone, insulin-like growth factor-I (IGF-I), dehydroepiandrosterone sulphate (DHEAS), and cortisol. RESULTS: During the training period significant increases took place in VO2max, muscle strength and EMG activity in both groups. The increases of the quadriceps femoris thickness were 6.5% (p < 0.001) in the healthy controls and 7.4% (p < 0.001) in the RA cases. The decreases in subcutaneous fat thicknesses were 9.9% (p < 0.001) and 12.3% (p < 0.001), respectively. No significant changes were found in serum hormone concentrations, but RA women showed lower levels of IGF-I during the whole follow-up. CONCLUSIONS: In RA women with stable disease the combined strength and endurance training increases physical fitness. Further the training increases muscle mass and decreases subcutaneous fat. It may decrease risks of cardiovascular diseases in RA patients. The intensive training had minor effects on serum hormone concentrations.

Class-3 porin protein of Neisseria meningitidis: cloning and structure of the gene.

The gene coding for the class-3 protein of Neisseria meningitidis was cloned and sequenced. The deduced amino acid (aa) sequence was highly homologous (50-78%) to those of other neisserial porin proteins. Alignment of the aa sequence of five neisserial porin proteins pinpointed several regions of identity or near identity. These are assumed to be membrane-spanning beta-strands. A comparison of the homologies between these neisserial porins showed that the class-3 protein is most closely related to the Neisseria gonorrhoeae P1A protein.

Production of pneumolysin, a pneumococcal toxin, in Bacillus subtilis.

We have expressed the pneumolysin gene of Streptococcus pneumoniae in Bacillus subtilis, both from its own promoter and as a fusion protein. The level of expression of pneumolysin from its own promoter was low. The protein produced was hemolytically active. A higher level of expression (about 10 micrograms/ml of culture) was achieved when either one of two C-terminal fragments (corresponding to amino acids 265-471 and 55-471, respectively) or the entire coding part of the pneumolysin gene were fused to the promoter and signal sequence-coding region of the alpha-amylase gene of Bacillus amyloliquefaciens. The C-terminal fusion peptides reacted with anti-pneumolysin serum, but were not hemolytically active. In both cases most of the peptide remained cell-associated. When the entire pneumolysin gene was fused to the signal sequence, a hemolytically active form of pneumolysin could be detected, and most of the product was found in a processed form in the culture supernatant. The full-length pneumolysin secreted from B. subtilis was partially purified and used as antigen in an enzyme immunoassay with rabbit anti-pneumolysin serum.

Distribution of group II phospholipase A2 protein and mRNA in rat tissues.

Group II phospholipase A2 (PLA2) is an acute-phase protein and an important component of the host defense against bacteria. In this study we investigated the distribution of PLA2 protein by immunohistochemistry and the distribution of mRNA of PLA2 by Northern blotting and in situ hybridization in rat tissues. PLA2 protein was localized in the Paneth cells of the intestinal mucosa, chondrocytes and the matrix of cartilage, and megakaryocytes in the spleen. By Northern blotting, mRNA of PLA2 was found in the gastrointestinal tract, lung, heart, and spleen. By in situ hybridization, PLA2 mRNA was localized in the Paneth cells of the small intestinal mucosa but in no other cell types. Our results show specific distribution of PLA2 in a limited number of cell types in rat tissues. The reagents developed in this study (the anti-rat PLA2 antibody and probes for Northern blotting and in situ hybridization of mRNA of rat PLA2) will provide useful tools for future studies concerning the role of PLA2 in various experimental disease models.

Correlation of asymmetry of visual field loss with optic disc topography in normal-tension glaucoma.

OBJECTIVE: To compare the differences in optic disc configuration with different stages of visual field loss in normal-tension glaucoma. DESIGN: Interocular pairwise comparisons. SETTING: Glaucoma clinic of a teaching hospital. PATIENTS: Thirteen patients with normal-tension glaucoma and asymmetric visual field loss of at least 2.5 dB in the mean defect of the visual field indexes. INTERVENTIONS: Areas under the optic disc profiles mapped from values for radial sections of the optic disc measured at intervals of 30 degrees and expressed as percentages of the area of a rectangle were obtained from stereophotographs with a computerized image analysis system. Visual fields were tested with automated perimetry (OCTOPUS), using program G1. MAIN OUTCOME MEASURE: Correlation analyses between the interocular differences in the areas under the optic disc profile and the interocular differences in the visual field indexes. RESULTS: The correlation coefficients between the interocular differences in mean defect and those of the area under the optic disc profile in the superior to temporal sections ranged from -.71 to -.61 (.007 < P < .028). The interocular differences in loss variance correlated with the differences in the area under the optic disc profile in the superior section (r = -.61, P = .0252). CONCLUSION: The differences in visual field loss between the two eyes in normal-tension glaucoma appear mainly to reflect morphometric changes in the superior half of the optic disc.

Dose response and duration of action of dorzolamide, a topical carbonic anhydrase inhibitor.

The multiple-dose, dose-response relationship and duration of action of the novel topical carbonic anhydrase inhibitor dorzolamide (previously known as MK-507) were investigated in a double-masked, randomized, placebo-controlled, parallel study in 73 patients with bilateral primary open angle glaucoma or ocular hypertension. Dorzolamide (0.7%, 1.4%, or 2%) or placebo was administered every 12 hours for 5 days and then every 8 hours for 7 days. Intraocular pressure was investigated with multiple 12-hour diurnal curves. All concentrations of dorzolamide demonstrated substantial lowering of intraocular pressure throughout the day when given twice daily (9% to 21%) or three times daily (14% to 24%). Although a dose-dependent response was observed immediately following the first dose, there were no significant differences between concentrations or dose response at either the twice or three times daily dosing regimen. Three times daily administration of 2% dorzolamide demonstrated a mean percent decrease in intraocular pressure of 18% to 22% throughout the day (mean decrease, 4.5 to 6.1 mm Hg). Dorzolamide appears to have substantial potential in the treatment of glaucoma and ocular hypertension.

The 20 kDa C-terminally truncated form of pertussis toxin subunit S1 secreted from Bacillus subtilis.

The subunit S1 of pertussis toxin (PT) was purified as the recombinant product BacS1 from the culture supernatant of a Bacillus subtilis strain containing a secretion vector with a DNA fragment coding for the mature subunit S1 inserted downstream of the signal sequence of the alpha-amylase gene. The method of purification was successive ion exchange and adsorption chromatography. BacS1 occurred in two forms (28 and 20 kDa) of which the truncated 20-kDa peptide was the main one in the supernatant. The truncated BacS1 was purified and shown to have the same NH2-terminus as the full-size (28 kDa) BacS1. It was also enzymatically active indicating correct conformation. The truncated BacS1 was also shown to elicit neutralizing and protective antibodies when injected into mice or rabbits.

Production and secretion of pertussis toxin subunits in Bacillus subtilis.

Pertussis toxin (PT) is a major component of today's acellular whooping cough vaccines. The use of acellular vaccines is predicted to increase sharply in the near future. There is therefore a need to produce PT in a way that makes its purification as easy as possible. Our approach was to express all five PT subunits individually in Bacillus subtilis. We have used vectors containing the promoter and signal sequences of the alpha-amylase gene of Bacillus amyloliquefaciens followed by an insert encoding the appropriate PT-subunit. All PT-subunits were secreted and found in the culture supernatant. The level of expression varied considerably: S1 and S5 were produced in large quantities whereas much smaller amounts of S2, S3 and S4 were found. The subunits were also present in the membrane fraction of the respective strains.

24-hour ambulatory blood pressure monitoring in elderly normotensive individuals and its reproducibility after one year.

To study ambulatory blood pressure (ABP) and its reproducibility in healthy normotensive elderly subjects, 34 individuals were randomly selected. Their ages were 65 years (n = 10), 70 years (n = 10), 75 years (n = 8) and 80 years (n = 6). SpaceLabs 90207 system was used and one initial and a follow-up measurement after one year was performed. It was found that 24h ABP easily could be recorded in elderly subjects. A mean of 97% of the measurements were successful and only two of 34 subjects dropped out because of measurement failures. Nocturnal blood pressures were lower in all age groups and in both sexes. The standard deviations of the differences between the baseline and one year measurements were for the daytime period 8/4 mmHg and for the nighttime period 12/8 mmHg. In conclusion, ABP is easily accepted as a clinical method in normotensive elderly subjects. In all subjects there is a reduction of the nocturnal blood pressure and the reproducibility of ABP after one year is good.

Toxic effects of human pancreatic and snake and bee venom phospholipases A2 on MCF-7 cells in culture.

The toxicity of phospholipase A2 (PLA2) has been suggested to be involved in the pathology of a number of severe diseases including septic shock and acute pancreatitis. However, testing the toxicity of these substances is difficult in vivo. In the present study we compared the toxicity of PLA2s from three snake venoms, bee venom and human pancreas on MCF-7 cells grown in culture. Tetrazolium microculture assays were developed to test the cytostatic and cytotoxic effects of PLA2 on MCF-7 cells. These tests are based on the ability of viable cells to reduce a tetrazolium-based compound MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] to a blue formazan product. Leakage of lactate dehydrogenase (LD) from the cells into the culture medium was also measured. There were marked differences in the toxicity of the PLA2s tested. Cobra (Naja mosambique mosambique) venom PLA2 was toxic to the cells at a concentration of 4.5 U/ml. Light microscopic changes were seen in the injured cells after 3 hr treatment. Sixty-seven per cent of cells were dead after 24 hr treatment. Treatment for 4 hr caused irreversible changes in the cells. Leakage of LD was noted from 4 hr onwards. Other snake (Crotalus adamanteus and Laticauda semifasciata) venom PLA2s, even after continuous exposure to 4.5 U/ml caused only slight decreases in values obtained in the MTT test. No morphologic changes suggesting a cytotoxic effect were seen. PLA2 from bee (Apis mellifera) venom had no toxic effect, either. Continuous exposure of cells to human pancreatic PLA2 caused a 15% decrease in the MTT-test.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary orbital amyloidosis localised to an extraocular muscle.

Primary, localised orbital amyloidosis has been reported previously in only 15 patients. A case with amyloidosis strictly localised to an extraocular muscle is presented.

Work with video display terminals among office employees. IV. Refraction, accommodation, convergence and binocular vision.

The present study is the fourth of a major epidemiologic health investigation on work with a video display terminal (VDT). The other studies showed that VDT operators replying to questionnaires have more eye discomfort than a reference group of office employees not employed in VDT work and that women have more eye discomfort, musculoskeletal complaints, headache, and skin disorders than men. Routine ophthalmologic examinations failed to establish any appreciable differences between the groups; for example, the prevalence of myopia was the same. In the present study, the VDT operators and referents were examined before and at the end of work sessions for changes in refraction, accommodation, convergence capacity, and binocular vision such as heterophoria and fusion range. No differences could be established between the VDT operators and the referents.

Work with video display terminals among office employees. III. Ophthalmologic factors.

The present ophthalmologic study is the third part of a major epidemiologic health investigation on work with a video display terminal (VDT). An initial study showed that VDT operators replying to a questionnaire reported more eye discomfort than a reference group not employed in VDT work and that women reported more eye discomfort, musculoskeletal discomfort, headache, and skin disorders than men, irrespective of whether or not they were employed in VDT work. In the present study the ophthalmologic history of eye diseases and eye discomfort yielded a much lower percentage response for symptoms and discomfort than the questionnaire, and, just as with visual acuity and refraction, there was no difference between the exposed and reference groups or between the men and women. The exposed subjects were found to be overcorrected in terms of presbyopia addition in relation to work distance. As regards ocular examination findings, low frequency rates were noted for pathological lens opacities. Opacities of this kind were slightly more frequent among the VDT operators than among the referents, but the difference was not statistically significant. There were no other differences in the ocular findings of the exposed and reference groups.