Aivars Lejnieks

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

AIMS The present study was undertaken to investigate the relationship between glyoxalase 1 (Glo1) enzyme activity and painful diabetic neuropathy (DN) in patients with diabetes mellitus. METHODS Glo1 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. RESULTS In 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. CONCLUSIONS Our 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.

Bone mineral density and mandibular residual ridge resorption.

PURPOSE This prospective, cross-sectional study evaluated the relationship between bone mineral density (BMD) and the width and height parameters of the mandibular residual ridge. MATERIALS AND METHODS BMD was determined in the lumbar spine and femoral necks by dual energy x-ray absorptiometry (DXA) in 45 edentulous, postmenopausal women (mean age, 72.08 ± 8.53 years) who had used conventional complete dentures for at least 3 years. Measurements of the mandibular residual ridge were performed using cone beam computed tomography (CBCT). Height and width measurements were performed in the midline and adjacent to the mental foramina. Data were analyzed with descriptive and analytic statistics. The relationship between BMD and mandibular height and width measurements was assessed using analysis of variance as well as linear and multivariate regression analyses. Eight patients were excluded from the study because they did not complete both of the required imaging analyses (DXA and/or CBCT). RESULTS There was no statistically significant relationship between BMD and mandibular bone height measurements in the midline and both regions of the mental foramina, and no statistically significant relationship existed between BMD and mandibular bone width measurements in the midline and both of the mental foramina regions. CONCLUSIONS Postmenopausal women with reduced general BMD do not appear to have a reduction in the size of the mandibular residual ridge.

A cross-sectional survey of urinary iodine status in Latvia

BACKGROUND AND OBJECTIVE A nationwide survey of schoolchildren was conducted to detect regional differences in urinary iodine excretion in Latvia and to compare the results with data from the newborn thyroid-stimulating hormone (TSH) screening database as well with the results of a similar study performed in Latvia 10 years ago. MATERIALS AND METHODS We conducted a cross-sectional school-based cluster survey of 915 children aged 9-12 years in 46 randomly selected schools in all regions of Latvia. Urine samples, questionnaires on the consumption of iodized salt and information on socioeconomic status were collected. TSH levels in newborns were also measured. RESULTS The median creatinine-standardized urinary iodine concentration (UIC) in our study was 107.3μg/g Cr. UIC measurements indicative of mild iodine deficiency were present in 31.6%, moderate deficiency in 11.9% and severe deficiency in 2.8% of the participants. The prevalence of iodine deficiency was the highest in the southeastern region of Latgale and the northeastern region of Vidzeme. The prevalence of TSH values >5mIU/L followed a similar pattern. The self-reported prevalence of regular iodized salt consumption was 10.2%. Children from urban schools had a significantly lower UIC than children from rural schools. CONCLUSIONS Our findings suggest that although the overall median UIC in Latvian schoolchildren falls within the lower normal range, almost 50% of the schoolchildren are iodine deficient, especially in urban schools and in the eastern part of Latvia. The absence of a mandatory salt iodization program puts a significant number of children and pregnant women at risk.

Iodine deficiency during pregnancy: a national cross-sectional survey in Latvia.

OBJECTIVE Low iodine intake during pregnancy may cause thyroid dysfunction, which results in inadequate fetal brain development. In the absence of a universal salt iodization programme, we conducted a nationwide survey of iodine deficiency in pregnant women in Latvia. DESIGN A countrywide twenty-cluster survey, with at least twenty women per cluster. Participants completed a questionnaire on dietary habits concerning iodine intake (n 739). Thyroid function (thyroid-stimulating hormone, free thyroxine and thyroperoxidase antibodies) was measured (n 550). Urinary iodine was measured using the ammonium persulfate method (n 696). SETTING The survey was performed in all regions of Latvia during the spring and autumn seasons in 2013. SUBJECTS Pregnant women (n 829). RESULTS The median creatinine (Cr)-standardized urinary iodine concentration (UIC) was 80·8 (interquartile range (IQR) 46·1-130·6) µg/g Cr or 69·4 (IQR 53·9-92·6) µg/l during pregnancy, and 81% of pregnant women had UIC levels below the WHO recommended range of 150-250 µg/g Cr. The UIC was lowest during the first trimester of pregnancy, 56·0 (IQR 36·4-100·6) µg/g Cr, reaching higher concentrations of 87·5 (IQR 46·4-141·7) µg/g Cr and 86·9 (IQR 53·8-140·6) µg/g Cr in the second and third trimesters, respectively. Women taking supplements containing ≥150 µg iodine (6·8% of respondents) had non-significantly higher UIC than did women without supplementation (96·2 v. 80·3 µg/g Cr, respectively, P=NS). Thyroperoxidase antibody concentration did not correlate significantly with UIC: Spearmans ρ=-0·012, P=0·78. CONCLUSIONS The median UIC indicates iodine deficiency in pregnant women in Latvia. Iodine supplementation (150 µg daily) and regular UIC monitoring should be suggested to overcome iodine deficiency and to reach the recommended levels without inducing autoimmune processes.

Hypertension in Latvia – Epidemiology and management

The aims of investigations were to assess the prevalence of arterial hypertension (AH) among Latvian population aged ⩾45 years and to evaluate the current AH management situation in Latvia. Four epidemiological databases (Dbases) for analyses were selected: Dbases of a randomized urban population of Riga city (in 1997) and Kuldiga region (in 2000), a Dbase of the DIASCREEN population selected by high risk to diabetes from those visiting family doctors (in 2003) and a Dbase of a Latvian population selected from those visiting family doctors during 3 days in 2005. The prevalence of AH in the urban population was 41.8±1.4% (with 61.2% for persons over age 45), in rural population 40.5±1.6% (with 63.7% for those aged above 45). Therapeutic control of AH for patients over 45 years with regular medicine intake differed significantly in three samples of the population analysed: Riga 7.2±2.7%, Kuldiga 9.9±1.6% and DIASCREEN 6.4±0.8%. The addition of another risk factor decreases the control rate, especially in a combination of AH and overweight. The most widely prescribed drugs are angiotensin‐converting enzyme inhibitors (ACEI) 31%, diuretics 21% and beta‐blockers 20% of patients. AH control rate in the case of monotherapy with ACEI was 6.9±0.9%, calcium antagonists 5.6±1.2%, beta‐blockers 12.5±2.0% and diuretics 3.8±1.4%. The current status of management of hypertension in Latvia is discussed.

Polymorphisms in MEN1 and DRD2 genes are associated with the occurrence and characteristics of pituitary adenomas

OBJECTIVE Although pituitary adenomas (PAs) affect a significant proportion of the population, only a fraction have the potential to become clinically relevant during an individuals lifetime, causing hormonal imbalance or complications due to mass effect. The overwhelming majority of cases are sporadic and without a clear familial history, and the genotype-phenotype correlation in PA patients is poorly understood. Our aim was to investigate the involvement of genes known for their role in familial cases on drug response and tumor suppression in the development and pathology of PAs in a patient group from Latvia. DESIGN The study included 143 cases and 354 controls, we investigated the role of single-nucleotide polymorphisms (SNPs) in seven genes (SSTR2, SSTR5, DRD2, MEN1, AIP, GNAS, and PRKAR1A) associated with pituitary tumor occurrence, phenotype, and clinical symptoms. METHODS Genotyping of 96 tag and nonsynonymous SNPs was performed in the genomic regions of interest. RESULTS We discovered a significant association (OR=17.8, CI 0.95=2.18-145.5, P=0.0002) between a rare MEN1 mutation (rs2959656) and clinically active adenoma in our patients. Additionally, rs7131056 at DRD2 was associated with a higher occurrence of extrasellar growth in patients with prolactinoma and somatotropinoma (OR=2.79, CI 0.95=1.58-4.95, P=0.0004). CONCLUSIONS rs2959656, a nonsynonymous variant in MEN1, is associated with the development of clinically active PA. Furthermore, rs7131056 in DRD2 contributes to either faster growth of the adenoma or reduced symptomatic presentation, allowing PAs to become larger before detection.

Pepsinogen testing for evaluation of the success of Helicobacter pylori eradication at 4 weeks after completion of therapy

BACKGROUND AND OBJECTIVE Pepsinogen levels in plasma are increased by inflammation in the gastric mucosa, including inflammation resulting from Helicobacter pylori infection. A decrease in pepsinogen II level has been suggested as a reliable marker to confirm the successful eradication of infection. The aim of our study was to evaluate the potential role of pepsinogens I and II, gastrin-17 and H. pylori antibodies in confirming successful eradication. MATERIAL AND METHODS Altogether 42 patients (25 women, 17 men), mean age 45 years (range 23-74), were enrolled. Pepsinogens I and II, gastrin-17 and H. pylori IgG antibodies were measured in plasma samples using an ELISA test (Biohit, Oyj., Finland) before the eradication and 4 weeks after completing the treatment. The success of eradication was determined by a urea breath test. RESULTS Eradication was successful in 31 patients (74%) and unsuccessful in 11 patients (26%). Pepsinogen II decreased significantly in both the successful (P=0.029) and unsuccessful (P=0.042) eradication groups. Pepsinogen I decreased significantly in the successful (P=0.025) but not the unsuccessful (P=0.29) eradication group. The pepsinogen I/II ratio increased in the successful eradication group (P=0.0018) but not in the group in which treatment failed (P=0.12). There were no differences in gastrin-17 or H. pylori antibody values. CONCLUSIONS A decrease in pepsinogen II levels cannot be used as a reliable marker for the successful eradication of H. pylori 4 weeks after the completion of treatment. The increase in pepsinogen I/II ratio reflects differences in pepsinogen production following the eradication irrespective of improvement in atrophy.

Alkylresorcinol Metabolites in Urine and Plasma as Potential Biomarkers of Rye and Wheat Fiber Consumption in Prostate Cancer Patients and Controls

Alkylresorcinols (ARs) are phytochemicals mainly associated with rye/wheat bran. Plasma ARs and their plasma and urine metabolites are considered as biomarkers for whole-grain rye/wheat intake. However ARs metabolite day and night variations have not been studied in prostate cancer patients yet. We investigated ARs metabolites 3, 5-dihydroxy-benzoic acid (DHBA), and 3-(3, 5-dihydroxyphenyl)-1-propanoic acid (DHPPA) in urine and plasma in prostate cancer patients and in control group. DHPPA in 12-h overnight urine correlated with the intake of rye bread and bread fiber across short time periods (3 days). Plasma DHPPA concentration was significantly greater in the prostate cancer group than in the control group. DHPPA and DHBA excretion was significantly higher in the overnight urine than in day urine in the prostate cancer group but not in the control group. DHPPA concentration in plasma in the prostate cancer group did not depend on the intake of rye bread in the previous day, suggesting an impaired metabolism of ARs metabolites in the prostate cancer group. The results of this study suggest DHPPA in 12-h overnight urine as a biomarker to estimate the intake of rye bread and bread fiber.

Dietary intake and major sources of plant lignans in Latvian men and women

Higher intake of lignans, diphenolic plant compounds, may reduce the risk of certain types of cancer and cardiovascular diseases. We assessed the dietary intake of four lignans: matairesinol, secoisolariciresinol, lariciresinol and pinoresinol. Furthermore, for the breads we supplemented the data with two more lignans: syringaresinol and medioresinol. Study subjects were 172 men and 97 women aged 40–75 years, residing in Riga, the capital of Latvia, all living at home, eating habitual food. Median total lignan intake was 2259 (range 1169–5759) μg/day. Secoisolariciresinol contributed 58% and syringaresinol 22% of lignan intake. Bread was the major food source of lignans in men (86%), whereas in women it was bread (57%) and flaxseed (35%).

Pulmonary arterial hypertension associated with connective tissue disease: Insights from Latvian PAH registry.

The term connective tissue disease (CTD) refers to a group of autoimmunedisorders that are classified among the systemic rheumatic diseases [1]. Pulmonary arterial hypertension (PAH) is a common and severe complication of such CTDs as systemic sclerosis (SSc), mixed CTD, systemic lupus erythematosus and, to a lesser extent, polymyositis-dermatomyositis, rheumatoid arthritis, antisynthetase syndrome and others [2–4]. CTD-associated PAH (CTD-PAH) is the secondmost prevalent type of PAH after idiopathic PAH (IPAH) inWestern world, affecting 0.5–15% of patients with CTDs and is one of the leading causes of mortality in patients suffering from SSc and mixed CTD [5–7]. PAH is defined as elevated mean pulmonary arterial pressure (mPAP) ≥25mmHg at rest with presence of pre-capillary pulmonary hypertension (PH), defined by pulmonary artery wedge pressure (PAWP) ≤15 mm Hg and a pulmonary vascular resistance (PVR) N3 Wood units in the absence of other causes of precapillary PH [2]. Patients with CTD-PAH are mainly females (representing ≈80% of all patients), are older (mean age at diagnosis 60 years), may present various comorbidities and have worse survival than IPAH patients [2]. Recently, a quantitative algorithm for predicting survival in patients with PAH has been derived from REVEAL registry and a simplified risk score calculator (a 22-point scoring system) has been developed and validated for everyday clinical use [8]. Although other PAH risk scoring systems exist, REVEAL risk score includes all PAH patients (including CTD-PAH), whereas other equations only apply to patients from certain PAH subgroups [9]. Despite increasing recognition of PAH in patients with CTDs, the diagnosis is often delayed, whichmay lead to unfavourable outcomes [7]. In general, patients with CTD suspected to have PAH should follow similar diagnosis algorithm as for other types of PH, including transthoracic echocardiography as an initial screening tool and subsequent right heart catheterization to confirm the diagnosis, assess disease severity and rule out left heart disease [2,7]. However, due to the high prevalence of both left heart disease and interstitial lung disease in CTD, the accurate diagnosis of PAH in this patient population is particularly challenging [2]. Although recommended CTD-PAH treatment algorithm is the same as for patients with IPAH and endothelin receptor antagonists, prostanoids and phosphodiesterase 5 inhibitors have shown favourable (albeit less pronounced than in case of IPAH) effects in CTD-PAH patients, treatment of these patients is more complex given the additional autoimmune disease burden requiring immunosuppressive therapy in most cases [2]. This is a prospective, observational, single-center study of the Latvian PAH registry. The study included 20 adult patients (≥18 years old) with newly (b3 months) diagnosed CTD-PAH in the time period from September 2007 until September 2016 (9 years). All patients had been diagnosed with CTD prior to screening by transthoracic echocardiography which measured estimated right