Regulation of protein kinase C by short term hyperglycaemia in human platelets in vivo and in vitro

Aims/hypothesis. Postprandial hyperglycaemia carries an increased risk of macrovascular disease even without Type II (non-insulin-dependent) diabetes mellitus. Chronic hyperglycaemia activates protein kinase C (PKC) in vitro and in vivo but it is not known whether PKC is regulated by short-term postprandial hyperglycaemia in vivo in humans. We investigated whether PKC is regulated in vivo in hyperglycaemic and hyperinsulinaemic infusion tests and correlated the results to stimulations in vitro. Methods. Protein kinase C regulation was measured in platelets obtained from 8 healthy subjects who were infused with glucose and insulin for 2 h attaining peak concentrations of 16 mmol/l glucose and in platelets from 8 healthy young subjects, 8 older subjects without diabetes, and 10 older subjects with Type II diabetes after incubation in vitro with 16 mmol/l glucose or glucose and insulin. For precise quantification, a shortened PKC β1 standard protein was generated by bacterial expression and PKC α, β1, β2 and δ isoenzyme values were measured by immunoblot analyses. Results. Hyperglycaemic and hyperinsulinaemic in vivo tests increased the amounts of PKC α, β1 and β2 in the membrane fraction of platelets to 225 ± 87 %, 164 ± 22 % and 302 ± 135 %, respectively, when compared with the baseline values in young healthy volunteers (n = 8, p < 0.05). The expression of PKC δ did not change. In comparison to the recombinant PKC β1 standard protein, 5 ng PKC β1/μg protein was measured before the test and 2 ng/μg were translocated to the membrane fraction after the infusion. No change in the absolute amount of PKC β1 was detected. In contrast, after incubation in vitro PKC was not regulated by glucose or glucose and insulin in 8 young healthy subjects (age 26 ± 0.7 years) and in 8 older, healthy subjects (age 64,8 ± 4 years) although 100 nmol/l 12-O-tetradecanoylphorbol 13-acetate caused maximal activation. In marked contrast, PKC β1 and PKC β2, but not PKC α or PKC δ, were increased in vitro in the membrane fraction by 292 ± 61 % and 432 ± 88 % (p < 0.05) in 10 subjects with Type II diabetes mellitus matched for age, sex and BMI. Conclusion/interpretation. We found that short-term hyperglycaemia activates PKC α, β1 and β2 in platelets of healthy persons making them potential candidates for mediating the increased cardiovascular risk of postprandial hyperglycaemia. Hyperglycaemia and hyperinsulinaemia did not cause short-term activation of PKC in platelets in vitro suggesting the existence of additional stimuli. Subjects with Type II diabetes showed a markedly altered reactivity of platelet PKC β in vitro indicating some diabetes-related regulation. [Diabetologia (2001) 44: 188–195] Received: 15 May 2000 and in revised form: 19 September 2000     

Association of Microsatellite Polymorphisms of the Human 14q13.2 Region with Type 2 Diabetes Mellitus in Latvian and Finnish Populations

A polymorphic microsatellite in intron 6 of the human proteasome core particle PSMA6 gene (HSMS006), and four other microsatellites localized upstream on human chromosome 14q13.2 (HSMS801, HSMS702, HSMS701, HSMS602), were genotyped in 104 type 2 diabetic patients and 129 age-matched control subjects from Latvia and replicated in 91 type 2 diabetic patients and 88 age-matched healthy control subjects from the Botnia Study in Finland. In type 2 diabetic patients from both populations the HSMS006 (TG)22 allele was two times more frequent compared to the control group. In the Latvian population the (CAA)8 allele of the HSMS602 marker was less frequent in the diabetic group, as was the (AC)24 allele of microsatellite HSMS801. Allele frequencies of the HSMS701 and 702 repeats were similar in healthy controls and type 2 diabetic patients. In conclusion, our data suggest that variants in the PSMA6 gene on chromosome 14q13.2 are associated with type 2 diabetes.     

Effects of pedagogical ideology on the perceived loudness and noise levels in preschools

High activity noise levels that result in detrimental effects on speech communication have been measured in preschools. To find out if different pedagogical ideologies affect the perceived loudness and levels of noise, a questionnaire study inquiring about the experience of loudness and voice symptoms was carried out in Iceland in eight private preschools, called “Hjalli model”, and in six public preschools. Noise levels were also measured in the preschools. Background variables (stress level, age, length of working career, education, smoking, and number of children per teacher) were also analyzed in order to determine how much they contributed toward voice symptoms and the experience of noisiness. Results indicate that pedagogical ideology is a significant factor for predicting noise and its consequences. Teachers in the preschool with tighter pedagogical control of discipline (the “Hjalli model”) experienced lower activity noise loudness than teachers in the preschool with a more relaxed control of behavior (public preschool). Lower noise levels were also measured in the “Hjalli model” preschool and fewer “Hjalli model” teachers reported voice symptoms. Public preschool teachers experienced more stress than “Hjalli model” teachers and the stress level was, indeed, the background variable that best explained the voice symptoms and the teacher''s perception of a noisy environment. Discipline, structure, and organization in the type of activity predicted the activity noise level better than the number of children in the group. Results indicate that pedagogical ideology is a significant factor for predicting self-reported noise and its consequences.     

A media player causes clinically significant telemetry interference with implantable loop recorders

Background  The implantable loop recorder is a useful diagnostic tool for intermittent cardiovascular symptoms because it can automatically record arrhythmias as well as a patient-triggered ECG. Media players have been shown to cause telemetry interference with pacemakers. Telemetry interference may be important in patients with implantable loop recorders because capturing a patient-triggered ECG requires a telemetry link between a hand-held activator and the implanted device. The purpose of this study was to determine if a media player causes interference with implantable loop recorders. Methods  Fourteen patients with implantable loop recorders underwent evaluation for interference with a 15 GB third generation iPod^TM (Apple, Inc.) media player. All patients had the Reveal Plus^TM (Medtronic, Inc.) implantable loop recorder. We tested for telemetry interference on the programmer by first establishing a telemetry link with the loop recorder and then, the media player was placed next to it, first turned off and then, on. We evaluated for telemetry interference between the activator and the implanted device by placing the activator over the device (normal use) and the media player next to it, first turned off and then, on. We made 5 attempts to capture a patient-triggered ECG by depressing the activator switch 5 times while the media player was off or on. Results  Telemetry interference on the programmer screen, consisting of either high frequency spikes or blanking of the ECG channel was seen in all patients. Telemetry interference with the activator resulted in failure to capture an event in 7 patients. In one of these patients, a green indicator light on the activator suggested that a patient-triggered event was captured, but loop recorder interrogation did not show a captured event. In the remaining 7 patients, an event was captured and appropriately recognized by the device at least 1 out of 5 times. Conclusion  A media player playing in close proximity to an implanted loop recorder may interfere with capture of a patient-triggered event. Patients should be advised to keep media players away from their implanted loop reorder.     

Association of reduced glyoxalase 1 activity and painful peripheral diabetic neuropathy in type 1 and 2 diabetes mellitus patients

AimsThe present study was undertaken to investigate the relationship between glyoxalase 1 (Glo1) enzyme activity and painful diabetic neuropathy (DN) in patients with diabetes mellitus.MethodsGlo1 activity and biochemical markers were determined in blood samples from 108 patients with type 1 diabetes, 109 patients with type 2 diabetes, and 132 individuals without diabetes as a control. Painful and painless peripheral DN was assessed and multivariate regression analysis was used to determine independent association of Glo1 activity with occurrence of painful DN.ResultsIn patients with type 1 and type 2 diabetes mellitus and painful DN compared to patients with painless DN, Glo1 activity was significantly reduced by 12 and 14%, respectively. The increase in Glo1 activity was significantly associated with reduced occurrence of painful DN after adjusting for confounders by multivariate analysis.ConclusionsOur results demonstrate for the first time that Glo1 activity is lower in patients with both types of diabetes mellitus who were diagnosed with painful DN. These data support the hypothesis that Glo1 activity modulates the phenotype of DN and warrant further investigation into the role of Glo1 in DN.     

Two HLA DRB 1 alleles confer independent genetic susceptibility to Graves disease: Relevance of cross‐population studies

Recent studies of Graves disease (GD) employing genome scanning techniques excluded the major histocompatibility complex as a contributor to disease liability. These findings contradict earlier population association studies. Our own earlier studies have also emphasized that genetic variation in human populations may give novel clues to disease liability and manifestations. To this end, we studied HLA class II alleles in 47 Latvian GD patients and 111 matched healthy controls. As expected, we found that DRB1*03 and DQA1*0501 (OR = 3.6, P = 0.029 and OR 2.35, P = 0.0373, respectively) were associated with GD. Unforeseen, DRB1*04 was found to be significantly increased in the patients compared to controls (OR 3.267, corrected P = 0.0319). The two DRB1 alleles conferred two non‐overlapping and independent susceptibilities to GD, in that only three patients were positive for both alleles, and the removal of each allele in turn resulted in only the other DRB1 allele showing significant association with the disease. There was no heterogeneity between the two patient groups (DRB1*03 positive and DRB1*04 positive) in clinical characteristics or disease manifestations. The phenotype DRB1*03 and/or DRB1*04 was found in 34/47 patients compared to 27/111 controls yielding an OR of 7.395 (P corrected = 0.000019). We examined the structural basis of DRB1 susceptibility to GD in light of this and previous studies, showing that DRB1*03, 04, and 08 were positively associated with the disease, whereas DRB1*07 was negatively associated. Differences in protein sequences were noted at residues 54, 57, 59, and 66; positions 54, 57, and 66 are on the same face of the α helix. The canonical arginine 54 is replaced by glutamine in DRB1*07. At position 66, asparagine in DRB1*03 and tyrosine in DRB1*04 are replaced by phenylalanine in DRB1*07. Residue 59, likely involved in pocket formation in the antigen binding groove, is modified by replacement of tyrosine in DRB1*03, 08, and 04 and by leucine in DRB1*07. The predicted differences in the shape and charges of the proximal reaches of the antigen binding groove between DRB1*07, and 03, 04, and 08, could determine whether or not a peptide from an auto‐antigen would be bound or not. Genetic variation among human populations may yield important clues to specific disease liability. © 2001 Wiley‐Liss, Inc.     

Assessment of skeletal muscle fatigue of road maintenance workers based on heart rate monitoring and myotonometry

Objective  

This research work is dedicated to occupational health problems caused by ergonomic risks. The research object was road building industry, where workers have to work very intensively, have long work hours, are working in forced/constrained work postures and overstrain during the work specific parts of their bodies. The aim of this study was to evaluate the work heaviness degree and to estimate the muscle fatigue of workers after one week work cycle. The study group consisted of 10 road construction and maintenance workers and 10 pavers aged between 20 and 60 years.