Why PRP works only on certain patients with tennis elbow? Is PDGFB gene a key for PRP therapy effectiveness? A prospective cohort study.

BACKGROUND: There is variability in individual response to platelet-rich plasma (PRP) therapy in tennis elbow treatment. Genetic variation, especially within genes encoding growth factors may influence the observed inter-individual differences. The purpose of this study was to identify polymorphic variants of the platelet-derived growth factor beta polypeptide gene (PDGFB) that determine an improved individual response to PRP therapy in tennis elbow patients. METHODS: This prospective cohort study was designed in accordance with STROBE and MIBO guidelines. A cohort of 107 patients (132 elbows, 25 bilateral) was studied, including 65 females (77 elbows) and 42 males (55 elbows), aged 24-64 years (median 46.00 ± 5.50), with lateral elbow tendinopathy treated with autologous PRP injection. The effectiveness of PRP therapy was recorded in all subjects at 2, 4, 8, 12, 24 and 52 weeks after PRP injection using the Visual Analog Scale (VAS), quick version of Disabilities of the Arm, Shoulder and Hand score (QDASH) and Patient-Rated Tennis Elbow Evaluation (PRTEE). In order to determine the PDGFB variants with the best response to PRP therapy, patient reported outcome measures were compared between individual genotypes within studied polymorphic variants (rs2285099, rs2285097, rs2247128, rs5757572, rs1800817 and rs7289325). The influence of single nucleotide polymorphisms on blood and PRP parameters, including the concentration of PDGF-AB and PDGF-BB proteins was also analyzed. RESULTS: Our analysis identified genetic variants of the PDGFB gene that lead to a better response to PRP therapy. The TT (rs2285099) and CC (rs2285097) homozygotes had higher concentration of platelets in whole blood than carriers of other genotypes (p = 0.018) and showed significantly (p < 0.05) lower values of VAS (weeks 2-12), QDASH and PRTEE (weeks 2-24). The rs2285099 and rs2285097 variants formed strong haplotype block (r2 = 98, D'=100). The AA homozygotes (rs2247128) had significantly lower values of VAS (weeks 4-52), QDASH and PRTEE (weeks 8, 12). CONCLUSIONS: PDGFB gene's polymorphisms increase the effectiveness of PRP therapy in tennis elbow treatment. Genotyping two polymorphisms of the PDGFB gene, namely rs2285099 (or rs2285097) and rs2247128 may be a helpful diagnostic tool while assessing patients for PRP therapy and modifying the therapy to improve its effectiveness.

Uremic pruritus and serum brain-derived neurotrophic factor in diabetic and non-diabetic haemodialysis patients.

INTRODUCTION: Even though uremic pruritus (UP) is very troublesome for haemodialysis (HD) patients, its underlying mechanism is not fully understood. AIM: Due to the possible role of brain-derived neurotrophic factor (BDNF) and its higher serum concentration in haemodialysis diabetic patients compared to non-diabetic ones, this study is aimed to evaluate its association with UP among diabetic and non-diabetic patients on maintenance HD. MATERIAL AND METHODS: A total of 94 patients were enrolled into the study. A visual analogue scale (VAS) was used to assess pruritus. RESULTS: No differences were found between the observed study groups in terms of BDNF serum concentration, other biochemical markers, sleep disturbances, or pruritus presentation. CONCLUSIONS: BDNF serum concentration was not found to be associated with UP among HD patients, however further studies are worth performing on a larger group of individuals.

Mesenchymal Stem Cells-Potential Applications in Kidney Diseases.

Mesenchymal stem cells constitute a pool of cells present throughout the lifetime in numerous niches, characteristic of unlimited replication potential and the ability to differentiate into mature cells of mesodermal tissues in vitro. The therapeutic potential of these cells is, however, primarily associated with their capabilities of inhibiting inflammation and initiating tissue regeneration. Owing to these properties, mesenchymal stem cells (derived from the bone marrow, subcutaneous adipose tissue, and increasingly urine) are the subject of research in the settings of kidney diseases in which inflammation plays the key role. The most advanced studies, with the first clinical trials, apply to ischemic acute kidney injury, renal transplantation, lupus and diabetic nephropathies, in which beneficial clinical effects of cells themselves, as well as their culture medium, were observed. The study findings imply that mesenchymal stem cells act predominantly through secreted factors, including, above all, microRNAs contained within extracellular vesicles. Research over the coming years will focus on this secretome as a possible therapeutic agent void of the potential carcinogenicity of the cells.

Relationship between CETP gene polymorphisms with coronary artery disease in Polish population.

The cholesteryl ester transfer protein (CETP) gene encodes a hydrophobic glycoprotein that plays a crucial role in the reverse transport of cholesterol. The aim of the present study was to determine whether CETP polymorphisms (rs1532624, rs247616 and rs708272) are associated with coronary artery disease (CAD) in a Polish population. Serum lipid levels and single nucleotide polymorphisms of CETP genes were determined in 494 subjects: 248 patients with premature CAD and 246 blood donors as controls. Selected polymorphisms were examined using TaqMan PCR analysis. We found that CAD risk was significantly higher for CC homozygotes and C allele carriers of the rs247616 polymorphism than for carriers with the T allele (OR 1.89, 95% CI 1.29-2.76, p = 0.001 and OR 1.51, 95% CI 1.14-1.99, p = 0.003) and likewise for the CC genotype of the rs1532624 polymorphism than for those with the A allele (OR 1.59, 95% CI 1.05-2.40, p = 0.026). Moreover, T allele carriers of the rs708272 polymorphism had significantly higher total cholesterol levels compared to CC homozygotes (p < 0.05) in the healthy controls. We also observed an allelic pattern, C(rs2477616)C(rs708272)C(rs1532624), which increased susceptibility to CAD by 43% (OR = 1.43, 95% CI 1.10-1.85, p = 0.006). In conclusion, the rs247616 and rs1532624 polymorphisms of CETP may modulate the risk of CAD in Polish population.

Pentoxifylline and Methylprednisolone Additively Alleviate Kidney Failure and Prolong Survival of Rats after Renal Warm Ischemia-Reperfusion.

Renal ischemia-reperfusion injury (IRI) induces local inflammation leading to kidney damage. Since pentoxifylline (PTX) and steroids have distinct immunomodulatory properties, we aimed to evaluate for the first time their combined use in IRI-induced acute kidney injury (AKI) and chronic kidney disease (CKD) in rats. In two experiments, PTX (100 mg/kg body weight subcutaneously) was administered 90 min prior to renal IRI or/and methylprednisolone (MP; 100 mg/kg body weight intramuscularly) was infused 60 min after reperfusion of a solitary kidney (AKI model: 45 min ischemia, 48 male Sprague-Dawley rats) or one kidney with excision of contralateral kidney 2 weeks later (CKD model: 90 min ischemia, 38 rats). Saline was infused in place of PTX or/and MP depending on the group. Renal function (diuresis, serum creatinine, creatinine clearance, sodium and potassium excretion, and urine protein/creatinine) was assessed at 48 h and 120 h post-IRI (AKI model) or 4, 16 and 24 weeks after IRI, along with survival analysis (CKD model). More evidently at early stages of AKI or CKD, treated animals showed higher glomerular filtration and diminished tubular loss of electrolytes, more so with PTX + MP than PTX or MP (serum creatinine (µmol/L) at 48 h of AKI: 60.9 ± 19.1 vs. 131.1 ± 94.4 vs. 233.4 ± 137.0, respectively, vs. 451.5 ± 114.4 in controls, all p < 0.05; and at 4 weeks of CKD: 89.0 ± 31.9 vs. 118.1 ± 64.5 vs. 156.9 ± 72.6, respectively, vs. 222.9 ± 91.4 in controls, p < 0.05 for PTX or PTX + MP vs. controls and PTX + MP vs. MP). Survival was better by >2-fold with PTX + MP (89%) vs. controls (40%; p < 0.05). PTX + MP largely protect from IRI-induced AKI and CKD and subsequent mortality in rats. This calls for clinical investigations, especially in kidney transplantation.

Upstream Stimulating Factor 1 (USF-1) Gene Polymorphisms and the Risk, Symptoms, and Outcome of Pediatric Ischemic Stroke.

BACKGROUND: Pediatric ischemic stroke is an important cause of morbidity and mortality. As previous studies of children after stroke showed, dyslipidemias were very common in Polish and other European populations. Thus, looking for genetic factors predisposing to pediatric stroke, its symptoms, and outcome, we have analyzed 2 polymorphisms of the upstream stimulating factor 1 (USF-1) gene. MATERIALS AND METHODS: The study group consisted of 82 children with stroke, 156 parents, and 146 controls. We used 2 alternative methods: the case-control model and the analysis of families using the transmission disequilibrium test. The 2 polymorphisms, rs2516839 and rs3737787, were genotyped using the TaqMan Pre-Designed SNP Genotyping Assay. The Statistica 10.0 software was used in all statistical analyses. RESULTS: We did not observe any statistical differences in genotype and allele frequencies between patients and controls. There were also no significant differences in the transmission of alleles from the parents to the affected children. However, we have observed that the TT genotype of the rs2516839 polymorphism was more common in patients with epilepsy and dysarthria, whereas the TT genotype of the rs3737787 polymorphism was more frequent in the group of patients with a decrease in intellectual functioning. CONCLUSIONS: Our study did not show any associations between the 2 analyzed polymorphisms of the USF-1 gene and pediatric ischemic stroke. However, we have observed an influence of specific genotypes on the outcome of stroke, including epilepsy, dysarthria, and a decrease in intellectual functioning.

The rs10757278 Polymorphism of the 9p21.3 Locus in Children with Arterial Ischemic Stroke: A Family-Based and Case-Control Study.

BACKGROUND: The association of 9p21.3 locus single nucleotide polymorphisms with arterial ischemic stroke in adults was demonstrated in many studies, but there are no studies in pediatric arterial ischemic stroke patients. We investigated whether the 9p21.3 locus polymorphism, namely rs10757278, is associated with the arterial ischemic stroke risk in children. METHODS: The study group consisted of 335 individuals: 80 children with arterial ischemic stroke, their biological parents (n = 122), and 133 children (age and sex matched) without any symptoms of arterial ischemic stroke as a control group. The rs10757278 polymorphism was genotyped using the TaqMan® Pre-designed SNP Genotyping Assay (Applied Biosystems). Two different study design models were used: family-based association test (transmission-disequilibrium test) and case-control model. RESULTS: There were no statistically significant differences in the distribution of genotypes and alleles of the rs10757278 polymorphism between groups of children with arterial ischemic stroke and controls. The frequency of both transmitted alleles in transmission-disequilibrium test analysis was identical (50%). The A allele carrier state (AA+AG genotype) was more frequent in arterial ischemic stroke children with hemiparesis than in patients without this symptom (94.5% versus 68.0%, P = .004). CONCLUSIONS: There is no evidence to consider the 9p21.3 locus polymorphism as a risk factor for childhood arterial ischemic stroke.

Efficacy of acarbose in different geographical regions of the world: analysis of a real-life database.

BACKGROUND: Alpha-glucosidase inhibitors are recommended in some international guidelines as first-line, second-line and third-line treatment options but are not used worldwide due to perceived greater effectiveness in Asians than Caucasians. METHODS: Data from ten post-marketing non-interventional studies using acarbose, the most widely used alpha-glucosidase inhibitor, from 21 countries, provinces and country groups were pooled. Effects on glycated hemoglobin (HbA1c ) were analysed for four major ethnicity/region groups (European Caucasians and Asians from East, Southeast and South Asia) to identify differences in the response to acarbose. RESULTS: The safety and efficacy populations included 67 682 and 62 905 patients, respectively. Mean HbA1c in the total population decreased by 1.12 ± 1.31% at the 3-month visit from 8.4% at baseline (p < 0.0001). Reductions in HbA1c , fasting plasma glucose and post-prandial plasma glucose were greater in patients with higher baseline values. Acarbose was well tolerated, with few episodes of hypoglycemia (0.03%) and gastrointestinal adverse events (2.76%). Data from 30 730 Caucasians from Europe and Asians from three major regions of Asia with non-missing gender/age information and baseline/3-month HbA1c data were analysed by multivariable analyses of covariance. After adjustment for relevant baseline confounding factors, Southeast and East Asians had slightly better responses to acarbose than South Asians and European Caucasians; however, the differences were small. CONCLUSIONS: Acarbose was effective in both European Caucasians and Asians; however, after adjustment for baseline confounding factors, significant small differences in response favoured Southeast and East Asians.

The rs2516839 Polymorphism of the USF1 Gene May Modulate Serum Triglyceride Levels in Response to Cigarette Smoking.

Single nucleotide polymorphisms (SNPs) of the USF1 gene (upstream stimulatory factor 1) influence plasma lipid levels. This study aims to determine whether USF1 SNPs interact with traditional risk factors of atherosclerosis to increase coronary artery disease (CAD) risk. In the present study serum lipid levels and USF1 gene polymorphisms (rs2516839 and rs3737787) were determined in 470 subjects: 235 patients with premature CAD and 235 controls. A trend of increasing triglycerides (TG) levels in relation to the C allele dose of rs2516839 SNP was observed. The synergistic effect of cigarette smoking and C allele carrier state on CAD risk was also found (SIM = 2.69, p = 0.015). TG levels differentiated significantly particular genotypes in smokers (1.53 mmol/L for TT, 1.80 mmol/L for CT and 2.27 mmol/L for CC subjects). In contrast, these differences were not observed in the non-smokers subgroup (1.57 mmol/L for TT, 1.46 mmol/L for CT and 1.49 mmol/L for CC subjects). In conclusion, the rs2516839 polymorphism may modulate serum triglyceride levels in response to cigarette smoking. Carriers of the C allele seem to be particularly at risk of CAD, when exposed to cigarette smoking.

Influence of education, marital status, occupation, and the place of living on skeletal status, fracture prevalence, and the course and effectiveness of osteoporotic therapy in women in the RAC-OST-POL Study.

The RAC-OST-POL population-based, epidemiological study provided data concerning the influence of education, marital status, occupation, and the place of living (residence) on skeletal status, fracture prevalence, and the course and effectiveness of osteoporotic therapy in 625 women older than 55 years, all of them recruited from the District of Raciborz in Poland. Their mean age was 66.4 ± 7.8 years. All the women completed a specially designed questionnaire. The skeletal status was assessed by femoral neck (FN) and total hip (TH) densitometry, using a Lunar DPX system (USA). In univariate analyses, taking into consideration the age differences, bone mineralization was dependent on marital status (Z score for FN and TH was significantly higher in widows than in divorcees; p < 0.05), place of residence (better results in rural areas; p < 0.05), and occupation (better in standing than sitting jobs; p < 0.05 for FN Z score and p < 0.01 for TH Z score). The multivariate model allowed us to verify that only place of living and type of occupation had a significant influence on densitometry results. In direct comparison, fracture prevalence seemed to be borderline significantly more common in widows (33.5%) and least common among divorcees (11.8%) (χ(2) = 6.9, df = 3, p = 0.07), but reanalysis performed after age adjustment excluded a true impact of marital status on fracture occurrence. Other factors did not affect fracture occurrence. Some factors influenced the use of medications for osteoporosis: higher level of education was associated with a more frequent use of vitamin D (χ(2) = 8.49, df = 3, p < 0.05) and of hormone replacement therapy (HRT) (χ(2) = 35.7, df = 3, p < 0.00001). HRT was most commonly used by unmarried women (30%) and least commonly by divorcees (11.8%) (χ(2) = 11.7, df = 3, p = 0.01). Vitamin D was more often used among women from the urban area of Raciborz than by those from surrounding rural areas (χ(2) = 9.2, df = 1, p < 0.01). The frequency of use of the three aforementioned medications was associated with the character of occupation. Women with sedentary jobs demonstrated the highest frequency of intake for vitamin D (χ(2) = 9.92, df = 3, p < 0.05) and HRT (χ(2) = 19.48, df = 3, p < 0.001) as well as for other antiresorptive medications (χ(2) = 8.18, df = 3, p < 0.05). We concluded that the results of the epidemiological study demonstrate that both skeletal status and use of antiosteoporotic medications were partially modified by analyzed social factors, whereas fracture prevalence was generally independent from those factors. These data suggest that education, marital status, place of living, and type of occupation may have impacts on implementation of osteoporosis-preventing health programs.

The -930A>G polymorphism of the CYBA gene is associated with premature coronary artery disease. A case-control study and gene-risk factors interactions.

Reactive oxygen species (ROS) are involved in the pathogenesis of atherosclerosis and coronary artery disease (CAD). NADPH oxidases are the main source of ROS in the vasculature. p22phox is a critical component of vascular NADPH oxidases and is encoded by the CYBA (cytochrome b245 alpha) gene. The -930A>G CYBA polymorphism (rs9932581:A>G) modulates the activity of the CYBA promoter, and influences CYBA transcriptional activity. The aim of the present study was to analyze a possible association between the -930A>G polymorphism and CAD and to search for gene-traditional risk factors interactions. 480 subjects were studied: 240 patients with premature CAD, 240 age and sex matched blood donors. The -930A>G polymorphism was genotyped using the TaqMan® Pre-designed SNP Genotyping Assay (Applied Biosystems). The -930G allele carrier state was a risk factor for CAD (OR 2.03, 95% CI 1.21-3.44, P=0.007). A synergistic effect of the -930G allele with overweight/obesity (BMI≥25) and cigarette smoking was found. The estimated CAD risk for BMI≥25 and the -930G allele interaction was about 160% greater than that predicted by assuming additivity of the effects, and about 40% greater for interaction of cigarette smoking and the -930G allele. Overweight/obesity was a risk factor for CAD only in the -930G allele carriers (P<10(-10)) but not in the AA homozygotes (P=1.00). In conclusion the -930A>G CYBA polymorphism is associated with CAD in the Polish population. The -930G allele carriers are particularly at risk of consequences of obesity and tobacco smoke exposure.

Calcium intake and osteoporosis: the influence of calcium intake from dairy products on hip bone mineral density and fracture incidence - a population-based study in women over 55 years of age.

OBJECTIVE: The incidence of osteoporosis increases with age and is most frequently observed in postmenopausal women. The objective of the present population-based cohort study was to assess the influence of Ca intake from dairy sources on hip bone mineral density and hip fracture incidence in a group of Polish women over 55 years of age. DESIGN: The main outcome measures included: bone mineral density, the number of previous fractures and the reported Ca intake from dairy sources, assessed by a diet questionnaire. SETTING: The RAC-OST-POL Study was conducted in the District of Raciborz in the south of Poland. SUBJECTS: The study was carried out in a group of 625 women, randomly recruited from the general population of women aged >55 years. RESULTS: Median Ca intake from dairy products was lower in the group of women with femoral neck T-score ≤-2·5 than in the group with T-score >-2·5 (275 v. 383 mg/d; P = 0·0019). For total hip score, the difference was close to borderline significance (P = 0·0698). Median Ca intake from dairy products was lower in the group of women with previous fractures than in those without fracture history (336 v. 395 mg/d; P = 0·0254). The main dairy source of Ca in the analysed group included milk drinks, rennet cheese and milk. CONCLUSIONS: Higher dairy Ca intake is recommended, since a number of the women analysed were unable to satisfy their Ca requirement exclusively from their diet.

Is TCF7L2 variant associated with non-diabetic chronic kidney disease progression? Results of a family-based study.

INTRODUCTION: It is assumed that genetic factors may play a significant role in CKD development. The aim of the study was to investigate the role of rs7903146 polymorphism in the TCF7L2 gene in development and progression of non-diabetic chronic kidney disease (CKD). MATERIAL/METHODS: 109 children and young adults with CKD caused by primary glomerulopathy and tubulointerstitial nephropathy, stages 3-5, and their 218 biological parents with no renal dysfunction were included in the study. We tested the transmission of alleles of rs7903146 polymorphism in the TCF7L2 gene from heterozygous parents to offspring affected with CKD using the transmission/disequilibrium test. We also analysed whether rs7903146 polymorphism had any impact on the loss of glomerular filtration rate. RESULTS: The rs7903146 polymorphism in TCF7L2 allele transmission from heterozygous parents to their affected children was not different from a random proportion expected for no association, in the whole group of subjects, and in the subgroups, depending on CKD aetiology. Lack of association between the analysed polymorphism and the loss of glomerular filtration rate was found in the total group of patients as well as in the subgroups, regarding the cause of CKD. CONCLUSIONS: This study found no association between rs7903146 polymorphism in the TCF7L2 gene and the increased risk for development of CKD caused by primary glomerulopathy and analysed tubulointerstitial nephropathy. The progression rate of CKD of non-diabetic aetiology does not depend on this polymorphism.

BCL11B, FLT3, NOTCH1 and FBXW7 mutation status in T-cell acute lymphoblastic leukemia patients.

T-cell acute lymphoblastic leukemia is a heterogeneous malignancy originating from developing lymphocyte precursors likely due to mutations in genes regulating thymocyte differentiation. Here, we characterized mutation status of BCL11B and FLT3 genes, presumably involved in T-ALL, together with FBXW7 and NOTCH1 as known players in T-ALL in 65 pediatric T-cell acute lymphoblastic leukemia patients. We also aimed at the assessment of prognostic value of NOTCH1 and FBXW7 mutations in ALL-IC BFM 2002 protocol. FLT3 and BCL11B mutations were detected in 3% and 2% of patients, respectively. FBXW7 mutations were observed in 8% of patients, while NOTCH1 was mutated in 40%. No correlation was found between NOTCH1 and FBXW7 mutations and traditionally used clinical factors or molecular features. In total we have detected nine mutations, which have not been previously described by others. Eight of them were found in NOTCH1 and one in BCL11B gene. Observed frequencies of NOTCH1 and FBXW7 are in line with previous reports, thus confirming postulated participation of these two genes in T-ALL pathomechanism. Moreover, we report on mutation frequency of FLT3 and BCL11B, not extensively studied in T-ALL so far. Finally, we suggest a putative role of BLC11B as an oncogene in T-ALL pathogenesis.

Substance P and intensity of pruritus in hemodialysis and peritoneal dialysis patients.

BACKGROUND: Uremic pruritus is a common complication in patients undergoing dialysis. The pathophysiological mechanisms of pruritus in patients with end-stage renal disease remain unknown. Neuropeptides, including substance P, are postulated to play an important role in the pathogenesis of pruritus. The aim of this study was to evaluate the role of substance P in uremic pruritus in patients on hemodialysis and peritoneal dialysis. MATERIAL/METHODS: We included 197 patients with end-stage renal disease: 54 on continuous ambulatory peritoneal dialysis and 143 on hemodialysis. Substance P, calcium, phosphorus, iron, ferritin, CRP, albumin, hemoglobin, Ca×P product, and iPTH level were determined in all participants. The correlation between these parameters and self-reported itching was evaluated in patients on hemodialysis in comparison with peritoneal dialysis patients. RESULTS: The incidence of itching was similar in hemodialysis and peritoneal dialysis patients. No differences in substance P level between the 2 groups were found. There was no correlation between substance P level and the incidence or intensity of pruritus in dialyzed patients. CONCLUSIONS: This study demonstrates that substance P does not play any important role in pruritus in hemodialysed and peritoneal dialyzed patients. However, further studies are necessary to assess the exact role of neuropeptides in uremic pruritus.

Epidemiological data on osteoporosis in women from the RAC-OST-POL study.

In the RAC-OST-POL study, epidemiological data were presented concerning osteoporosis in 625 women older than 55 yr coming from the District of Raciborz in Poland. The mean age was 66.4 ± 7.8 yr. All the women fulfilled a questionnaire, gathering data on clinical risk factors of osteoporosis. Femoral neck (FN) and total hip (TH) were measured. The mean value of bone mineral density for FN was 0.862 ± 0.129 g/cm(2), T-score -1.25 ± 0.92, and Z-score 0.039 ± 0.78, whereas the respective values for TH were 0.945 ± 0.149 g/cm(2), -0.47 ± 1.19, and 0.52 ± 0.98. T-score for FN below -2.5 was noted in 59 women (9.5%) and for TH in 23 women (3.7%). One hundred seventy six women reported prior osteoporotic fracture(s) (28.2%). Falls were the most common clinical risk factor. The number of clinical risk factors was significantly higher in subjects with fracture history than in those without fracture records. The only first-line antiresorptive medications, used in the therapy for osteoporosis, included alendronate-42 subjects (6.7%). Estrogen therapy was prescribed in 135 women and 7 were treated with calcitonin. Calcium was administered in 94 patients and vitamin D in 84 women. In all the women on therapy, Z-score values were significantly lower than in untreated women. Concluding, the results of our epidemiological study demonstrate low treatment rate in women with history of low trauma fracture. Effective strategies are needed for prevention, especially in regard to falls, and management of this disease, in particular for improvement of the treatment rates in affected women with prior fracture, in general.

1936A→G (I646 V) polymorphism in the AKAP10 gene encoding A-kinase-anchoring protein 10 in very long-lived poles is similar to that in newborns.

UNLABELLED: BACKGROUND/STUDY CONTEXT: The common 1936A→G transition (rs203462) in the AKAP10 gene encoding the A-kinase-anchoring protein 10 has been recently associated with negative prognosis in the aging European American population (60 to 79 years old). The aim of this study was to see the effects of this transition on allele frequency in very long-lived Poles. METHODS: AKAP10 genotype and allele distributions were analyzed in Polish subjects: 148 nonagenarians (95 to 103 years old) and 200 healthy newborn controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Distributions were separated according to gender and χ(2) tests used to analyze possible differences. RESULTS: No significant differences were found in genotype or allele distribution between the age groups, for either gender. Percentages of GG AKAP10 homozygotes were slightly greater in the very old subjects than in the newborns (12.2% vs. 9.0%, respectively), and the G allele percentages were very similar (males, 30.7% and 33.0%; females, 34.1% and 35.8%; respectively). CONCLUSION: The authors conclude that differences in study results between European Americans (60 to 79 years old) and Poles (≥95 years old) result from either (1) geographical location; or (2) the influence of this polymorphism on groups of people differing in genetic background or environmental history; or (3) the time window affected, including extreme age. Further studies with full age-frequency distributions are needed to clarify these results.

[Carbohydrate sweeteners and obesity]. / Weglowodanowe substancje slodzace a otylosc.

The U.S. prevalence of obesity increases since the mid-70s of the 20th century. Around that time high-fructose corn syrup (HFCS)--mixture of fructose and glucose was introduced as a sweetener replacing sucrose in the food production. HFCS containing 55% fructose and 42-45% glucose (HFCS55) has dominated the American soft drink industry and HFCS has recently become commonly used in Poland. The coincidence of HFCS introduction and obesity epidemic raised widely publicized suspicions of a causal relationship between the two. As a possible mechanism, a higher content of fructose in the HFCS55, as compared with sucrose was suggested -fructose is known to increase serum uric acid level, induce hepatic lipogenesis and not stimulate postprandial hyperinsulinemia, a main activator of leptin release. Few comparative studies of HFCS and sucrose have largely failed to reveal any different impacts on the metabolic parameters, yet they were mainly short-term. It has been recently shown that obesity is linked with changes in the intenstinal flora. Among the causes of allegedly different effects of sucrose and HFCS on metabolism, their influence on the gut microbiome has not been examined. Some bacterial types do not hydrolyze sucrose which may determine different compositions of gut flora with the use of both sweeteners. Studies involving quantitative analysis of bacterial DNA in the stool, both in animals and in humans, shall shed light on the issue that has recently so much absorbed the U.S. public opinion.

Imeglimin: a new antidiabetic drug with potential future in the treatment of patients with type 2 diabetes.

Imeglimin (IMEG) is the first drug of the "glimin" group. Glimin is a new group of hypoglycaemic drugs for the treatment of patients with type 2 diabetes mellitus (T2DM). The chemical structure and action mechanism of the drug are presented in the paper. Imeglimin is unique and different in action compared to other hypoglycaemic drugs. Imeglimin has been shown to have a beneficial effect on 3 key pathogenetic elements of T2DM, i.e., 1. increased gluconeogenesis, 2. inadequate glucose-induced insulin secretion by beta cells, and 3. peripheral insulin resistance. The peak effect on fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) levels of IMEG is reached after 16 weeks of treatment. Subjects receiving IMEG at 1000- and 1500-mg doses twice daily also achieved significantly greater reductions in fasting plasma glucose (FPG) levels at week 24 compared to the placebo group (IMEG in humans causes increased insulin secretion as well as reductions in fasting plasma glucose and glycated haemoglobin). This paper also presents the pharmacokinetics of IMEG action, clinical evidence for its efficacy, results of phase II and III clinical trials, and drug tolerability. Our paper seems to show that IMEG, with its novel mechanism of action, has a chance to improve treatment results in a larger population of T2DM patients.

Fabry disease - a genetically conditioned extremely rare disease with a very unusual course.

Fabry disease (FD) is a rare lysosomal storage disease. FD is caused by the presence of a deleterious mutation in the GLA gene encoding the enzyme alpha galactosidase A (αGAL A) on the X chromosome. The accumulation of Gb3 and lyso-GL-3 in nerve fiber cells, endothelium, vascular muscle cells, mesangial cells, podocytes, renal tubular epithelial cells and cardiomyocytes is the most important pathogenetic factor. The rate of disease progression depends on residual conserved enzymatic activity. In this article we present an example of a 25-year-old patient with FD with an initial asymptomatic course. The first manifestation of FD developed in the third decade of life. These include high blood pressure, urinary changes and grade V renal failure, requiring renal replacement therapy. The diagnosis was made very late, when renal failure and cerebro-cardiac complications occurred, including stroke and dangerous cardiac tamponade.