Effect of a high-fat high-fructose diet on the composition of the intestinal microbiota and its association with metabolic and anthropometric parameters in a letrozole-induced mouse model of polycystic ovary syndrome.

OBJECTIVE: It has been suggested that dysbiosis of the gut microbiota is associated with the pathogenesis of Polycystic Ovary Syndrome (PCOS), and that improper diet can aggravate these changes. This study thus aimed to investigate the effects of a high-fat/high-fructose (HF/HFr) diet on the gut microbial community and their metabolites in prepubertal female mice with letrozole (LET)-induced PCOS. We also tested the correlations between the relative abundance of microbial taxa and selected PCOS parameters. RESEARCH METHODS & PROCEDURES: Thirty-two C57BL/6 mice were randomly divided into four groups (n = 8) and implanted with LET or a placebo, with simultaneous administration of a HF/HFr diet or standard diet (StD) for 5 wk. The blood and intestinal contents were collected after the sacrifice. RESULTS: Placebo + HF/HFr and LET + HF/HFr had significantly higher microbial alpha diversity than either group fed StD. The LET-implanted mice fed StD had a significantly higher abundance of Prevotellaceae_UCG-001 than the placebo mice fed StD. Both groups fed the HF/HFr diet had significantly lower fecal levels of short-chain fatty acids than the placebo mice fed StD, while the LET + HF/HFr animals had significantly higher concentrations of lipopolysaccharides in blood serum than either the placebo or LET mice fed StD. Opposite correlations were observed between Turicibacter and Lactobacillus and the lipid profile, CONCLUSION: HF/HFr diet had a much stronger effect on the composition of the intestinal microbiota of prepubertal mice than LET itself.

Long-term effects of COVID-19 on the endocrine system - a pilot case-control study.

Background: Coronavirus disease 2019 (COVID-19) has permanently changed the world. Despite having been a pandemic for nearly 3 years, the mid- and long-term complications of this disease, including endocrine disorders, remain unclear. Our study aimed to evaluate the lasting effects of COVID-19 on the endocrine system 6 months after initial infection. Methods: We compared patients who underwent COVID-19 to age- and sex-matched subjects from a population-based study conducted before the pandemic. We evaluated differences in multiple parameters related to metabolism and the endocrine system including fasting glucose, insulin, lipids, body composition, thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), anti-thyroglobulin (aTG) and anti-thyroid peroxidase (aTPO) antibodies, prolactin, cortisol, testosterone, and estradiol. Results: We found significantly lower levels of fT3 and fT4, accompanied by higher levels of TSH and aTPO antibodies, in COVID-19 survivors. Moreover, we found that patients who underwent SARS-CoV2 infection had higher levels of prolactin and lower levels of testosterone than controls. Interestingly, differences in testosterone levels were observed only in male subjects. We did not detect significant differences in body composition or metabolic and glycemic parameters between cases and controls, except for significantly higher values of the HOMA2-B index in COVID-19 survivors. Conclusion: Our study indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might have long-term consequences on the endocrine system, including the suppressed function of the thyroid gland, prolactin, and male sex hormone secretion. Moreover, we showed that in a 6-month follow-up, COVID-19 had no consequences on glycemic parameters, lipid profiles, liver function, body composition, cortisol levels, and estradiol levels.

The Effect of the COVID-19 Pandemic on Self-Reported Health Status and Smoking and Drinking Habits in the General Urban Population.

The coronavirus disease 2019 pandemic created a significant crisis in global health. The aim of the study was to compare the impact of the COVID-19 pandemic on self-rated health status and smoking and alcohol habits. The Bialystok PLUS cohort study was conducted in 2018-2022. A total of 1222 randomly selected city residents were examined and divided into two groups: before and during the COVID-19 pandemic. The participants' lifestyle habits and medical history were collected from self-reported questionnaires. The Alcohol Use Disorders Identification Test (AUDIT) and the Fagerström Test for Nicotine Dependence (FTND) were used to assess the degree of alcohol and nicotine dependence. The survey revealed a reduced frequency of reported allergies vs. an increased frequency of reported sinusitis and asthma; increased incidence of declared hypercholesterolemia and visual impairment; a reduced number of cigarettes smoked per day, lower FTND score, and a greater desire to quit smoking in the next six months; and an increase in hs-CRP and FeNO levels in the population during the pandemic compared to the pre-pandemic population. The COVID-19 pandemic had a measurable impact on the general population's prevalence of certain medical conditions and lifestyle habits. Further research should continue to examine the long-term health implications of the pandemic.

Impact of COVID-19 in Patients with Lung Cancer: A Descriptive Analysis.

The COVID-19 pandemic poses a challenge to health systems worldwide. Limiting healthcare availability may delay early diagnosis and worsen the treatment effects of various diseases, including oncological diseases. We analyzed patients presenting to the 2nd Department of Lung Diseases and Tuberculosis in Bialystok, Poland, with suspicion of lung cancer 12 months prior to the COVID-19 pandemic (pre-COVID-19) and, similarly, 12 months after the outbreak of the pandemic (mid-COVID). In total, 320 patients were analyzed-132 prior to and 188 after the COVID-19 outbreak. During the COVID-19 period, there was a lower percentage of patients presenting with ECOG performance status 0-1, with a noticeably increased percentage of patients with ECOG PS ≥2. The disease's clinical stage (CS) was higher on admission during COVID-19. We observed more use of immunotherapy and more deaths before the start of treatment during the COVID-19 period. These results provide insight into the early effects of the COVID-19 pandemic on lung cancer patients and underscore the importance of conducting further studies to assess the long-term effects of the COVID-19 pandemic on this population.

Evaluation of Free Light Chains (FLCs) Synthesis in Response to Exposure to SARS-CoV-2.

The aim of this study is to assess the synthesis of kappa (κ) and lambda (λ) free light chains (FLCs) in the serum of patients with COVID-19. All the 120 serum samples were collected from patients with COVID-19 and from healthy controls (vaccinated and non-vaccinated against SARS-CoV-2). FLCs, IgG total, IgG4, IgG anti-Nucleocapsid (N), anti-spike S1 receptor binding domain (S-RBD) antibodies and IL-6 were measured according to the manufacturers' instructions. The concentrations of anti-N IgG, IgG total, IgG4 and IL-6 were elevated in the COVID-19 group in comparison to the vaccinated and non-vaccinated controls. The levels of anti-S-RBD IgG and κFLC were increased in COVID-19 and healthy vaccinated patients when compared to non-vaccinated controls. λFLC concentration was higher in the COVID-19 group than in the non-vaccinated group. The κ:λ ratio was lower in both COVID-19 and non-vaccinated groups in comparison to vaccinated controls. κFLC correlated with all tested parameters (anti-S-RBD IgG, anti-N IgG, λFLC, κ:λ ratio, IgG total, IgG4 and IL-6) except CRP, whereas λFLC correlated with all examined parameters except IgG4. Elevated levels of FLCs in COVID-19 and healthy vaccinated against SARS-CoV-2 patients, as well as the correlation between free light chains with specific anti-SARS-CoV-2 antibodies and IL-6, reflect hyperactivation of the immune system after contact with coronavirus. Furthermore, it seems that serum levels of FLCs might be used as predictive markers of COVID-19. Our findings suggest that free light chains are involved in SARS-CoV-2 infection. However, understanding the exact mechanism requires further investigation.

Inflammatory and thrombotic parameters associated with the COVID-19 course in Poland (SARSTer study).

PURPOSE: The aim of the study was to assess the coagulation and inflammatory markers connected with severe course of COVID-19 and no clinical improvement. MATERIAL AND METHODS: The study population included 2590 adult patients, diagnosed with COVID-19, selected from the SARSTer national database - an ongoing project led by the Polish Association of Epidemiologists and Infectiologists and supported by the Medical Research Agency. Clinical and laboratory parameters, such as C-reactive protein (CRP), white blood cells (WBCs), neutrophil and lymphocyte count, procalcitonin, ferritin, interleukin-6 (IL-6), D-dimer concentration and platelet (PLT) count were analyzed before and after treatment (remdesivir, tocilizumab, dexamethasone, anticoagulants). RESULTS: Significant differences between patients with mild and severe course of the disease were observed in all examined parameters before treatment (p â€‹< â€‹0.05). After treatment only ferritin concentration did not differ significantly. In patients with pulmonary embolism, CRP concentration, neutrophil count, D-dimer and IL-6 concentration were significantly higher than in patients without embolism (p â€‹< â€‹0.05). The significant differences between the groups with and without fatal outcome were observed within all analyzed parameters. Significant differences in all examined parameters before treatment were observed between patients with and without clinical improvement (p â€‹< â€‹0.05). Multivariate logistic regression showed that no clinical improvement was associated with: IL-6>100 â€‹pg/ml (OR-2.14), D-dimer concentration over 1000 â€‹ng/ml (OR-1.62) and PLT count below 150,000/µl (OR-1.57). CONCLUSIONS: Severe course of the disease is associated with lower PLT and lymphocyte count, higher D-dimer, CRP, neutrophil count and IL-6 concentration. The best predictors of no clinical improvement in COVID-19 are: IL-6>100 â€‹pg/ml, D-dimer>1000 â€‹ng/ml and PLT<150,000/µl.

Associations of plasma betaine, plasma choline, choline intake, and MTHFR polymorphism (rs1801133) with anthropometric parameters of healthy adults are sex-dependent.

BACKGROUND: Choline and its metabolites apppear to have relationships with body mass index (BMI), body fat, and body weight, but the research results have proved inconsistent. We thus investigated the associations of plasma levels of trimethylamine N-oxide (TMAO), choline, and betaine with anthropometric measurements, including modulatory effects of genetics and diet. METHODS: The study was performed on a group of 421 adults, aged 20-40 years, who had been recruited in Poland. Plasma concentrations of choline, betaine, and TMAO were determined using reverse-phase ultra-high-performance liquid chromatography electrospray ionisation mass spectrometry. The following polymorphisms were genotyped using TaqMan probes: rs180113 (MTHFR), rs70991108 (DHFR), rs2236225 (MTHFD1), and rs7946 and rs12325817 (PEMT). We employed multivariate linear regression to examine the associations between anthropometric measurements, one-carbon metabolism metabolites, and genotypes. RESULTS: Higher plasma choline was associated with higher BMI (ß = 0.17; p < 0.01), body weight (ß = 0.11; p < 0.05), body fat mass (FM) (ß = 0.10; p < 0.05), and waist circumference (WC) (ß = 0.14; p < 0.01), whereas higher choline intake was associated with lower body FM (ß = -0.14; p < 0.01) and lower WC (ß = -0.12; p < 0.01). After stratification by sex, plasma betaine was found to be associated with lower BMI (ß = -0.20; p < 0.05) and body weight (ß = -0.16; p < 0.05) in men only, whereas choline intake was associated with lower body FM (ß = -0.19; p < 0.05) and waist-to-hip ratio (WHR) (ß = -0.19; p < 0.05) and MTHFR CC genotype was associated with WHR (ß = 0.15; p < 0.05) in women only. CONCLUSIONS: Higher plasma betaine and higher dietary choline are associated with lower FM and body weight, whereas higher plasma choline is positively associated with body weight status and adiposity. Moreover, these associations appear to be sex-specific.

The Many Faces of Immune Checkpoint Inhibitor-Associated Pneumonitis: 4 Case Reports.

BACKGROUND Advanced non-small cell lung cancer has poor prognosis and low survival. Immunotherapy with the use of immune checkpoint inhibitors is a relatively new method of treatment that offers a chance to significantly extend the survival and quality of life of patients over that obtained with conventional chemotherapy. One of the complications of immunotherapy is immune checkpoint inhibitor-related pneumonitis. CASE REPORT We analyzed the available medical data on the treatment of 22 patients with non-small cell lung cancer who were treated in our clinic and qualified for immunotherapy with one of the anti-PD-1/anti-PD-L1 agents: nivolumab, atezolizumab, or pembrolizumab. In this group of patients treated with immune checkpoint inhibitors, 4 patients experienced immune checkpoint inhibitor-related pneumonitis. CONCLUSIONS Immune checkpoint inhibitor-related pneumonitis is a rare but potentially life-threatening complication of immune therapy. It can manifest in many ways, from asymptomatic to severe cases, which require quick action and treatment. Knowing the spectrum of symptoms and being alert to the possibility of such a complication is an important skill for doctors who use immunotherapy in their patients.

Severe Breakthrough COVID-19 Cases during Six Months of Delta Variant (B.1.617.2) Domination in Poland.

The emergence of a highly transmissible and a more pathogenic B.1.617.2 (delta) variant of SARS-CoV-2 has brought concern over COVID-19 vaccine efficacy and the increased risk of severe breakthrough infections. The objective of this study was to assess the frequency and the clinical characteristics of severe breakthrough COVID-19 cases recorded in 10 Polish healthcare units between 1 June and 31 December 2021, a period during which a rapid surge in the share of B.1.617.2 infections was seen, while a significant number of populations were already fully vaccinated. Overall, 723 individuals who completed the initial vaccination regime (fully vaccinated group) and an additional 18 who received a booster dose were identified­together, they represented 20.8% of all the COVID-19 patients hospitalized during the same period in the same healthcare institutions (0.5% in the case of a group that received a booster dose). Although laboratory and clinical parameters did not differ between both groups, patients who received a booster tended to have lower CRP, IL-6, PCT, and d-dimer levels and they required oxygen therapy less frequently. The most common early COVID-19 symptoms in the studied group were fatigue, cough, fever (>38 °C), and dyspnea. Individuals with no detectable anti-spike IgG antibodies constituted 13%; the odds of being a humoral non-responder to the vaccine were increased in patients aged >70 years. Fully vaccinated patients hospitalized after more than 180 days from the last vaccine dose were significantly older and they were predominantly represented by individuals over 70 years and with comorbidities, particularly cardiovascular disease. Contrary to mRNA vaccines, most patients vaccinated with adenoviral vector vaccines were infected within six months. A total of 102 fatal cases (14% of all deaths among vaccinated individuals; 0.7% in the case of a group that received a booster dose) were recorded, representing 17.6% of all the COVID-19 fatalities recorded in June−December 2021 in the considered healthcare units. The odds of death were significantly increased in men, individuals aged >70 years, patients with comorbidities, and those identified as humoral non-responders to vaccination; in fully vaccinated patients the odds were also increased when the second vaccine dose was given >180 days before the first COVID-19 symptoms. The mortality rate in immunocompromised subjects was 19%. The results indicate that compared to vaccinated individuals, severe COVID-19 and deaths in the unvaccinated group were significantly more prevalent during the B.1.617.2-dominated wave in Poland; and, it highlight the protective role of a booster dose, particularly for more vulnerable individuals.

ß-glucuronidase activity is associated with carbohydrate metabolism but not with androgen status in overweight and obese women with polycystic ovary syndrome.

OBJECTIVES: The aim of this study was to evaluate the relationship between ß-glucuronidase and androgen levels in overweight and obese women with polycystic ovary syndrome (PCOS). The connection between ß-glucuronidase, the abundance of selected gut bacteria, carbohydrate metabolism, and diet quality was also determined. METHODS: This cross-sectional study was conducted with 56 women with a mean age of 29.14 ± 5.11 y and a mean body mass index (BMI) of 34.15 ± 5.72 kg/m2. Anthropometrical parameters, fecal ß-glucosidase activity, and selected food frequency intake were measured. RESULTS: Women with better quality diets, apart from lower BMI and better carbohydrate metabolism parameters, had more abundant Faecalibacterium prausnitzii and Akkermansia muciniphila. Two-hour oral glucose tolerance test (OGTT-2h-glu; mg/dL) was the main predictor of ß-glucuronidase activity and there was no relationship between ß-glucuronidase activity and androgen levels. Non-Healthy Diet Index-14 (nHDI-14) was the main predictor for A. muciniphila, Bifidobacteriu. longum, and F. prausnitzii abundance. QUICKI was a significant predictor of A. muciniphila abundance and OGTT-2h-glu was a significant predictor of F. prausnitzii abundance. CONCLUSION: There was no relationship between ß-glucuronidase activity and androgen levels in overweight and obese women with PCOS, but ß-glucuronidase activity may be an important factor in carbohydrate metabolism. Modulation of the abundances of F. prausnitzii, A. muciniphila, and B. longum using special diets should thus be considered a promising intervention.

Mitochondrial DNA and Epigenetics: Investigating Interactions with the One-Carbon Metabolism in Obesity.

Mitochondrial DNA copy number (mtDNAcn) has been proposed for use as a surrogate biomarker of mitochondrial health, and evidence suggests that mtDNA might be methylated. Intermediates of the one-carbon cycle (1CC), which is duplicated in the cytoplasm and mitochondria, have a major role in modulating the impact of diet on the epigenome. Moreover, epigenetic pathways and the redox system are linked by the metabolism of glutathione (GSH). In a cohort of 101 normal-weight and 97 overweight/obese subjects, we evaluated mtDNAcn and methylation levels in both mitochondrial and nuclear areas to test the association of these marks with body weight, metabolic profile, and availability of 1CC intermediates associated with diet. Body composition was associated with 1CC intermediate availability. Reduced levels of GSH were measured in the overweight/obese group (p = 1.3∗10-5). A high BMI was associated with lower LINE-1 (p = 0.004) and nominally lower methylenetetrahydrofolate reductase (MTHFR) gene methylation (p = 0.047). mtDNAcn was lower in overweight/obese subjects (p = 0.004) and independently correlated with MTHFR methylation levels (p = 0.005) but not to LINE-1 methylation levels (p = 0.086). DNA methylation has been detected in the light strand but not in the heavy strand of the mtDNA. Although mtDNA methylation in the light strand did not differ between overweight/obese and normal-weight subjects, it was nominally correlated with homocysteine levels (p = 0.035) and MTHFR methylation (p = 0.033). This evidence suggests that increased body weight might perturb mitochondrial-nuclear homeostasis affecting the availability of nutrients acting as intermediates of the one-carbon cycle.

Comparison of Associations between One-Carbon Metabolism, Lipid Metabolism, and Fatty Liver Markers in Normal-Weight and Overweight People Aged 20-40 Years.

The aim of the present study was to compare biomarkers of one-carbon metabolism (OCM), lipid metabolism, and fatty liver in people with normal and increased body weight. The study was performed on 421 participants, aged 20-40 years, enrolled in Poznan, Poland, in 2016-2018. Choline and betaine intakes were assessed. DNA samples were genotyped for polymorphisms of phosphatidylethanolamine N-methyltransferase (PEMT; rs7946 and rs12325817), methylene tetrahydrofolate reductase (MTHFR; rs180113), methylenetetrahydrofolate dehydrogenase (MTHFD1; rs2236225), and dihydrofolate reductase (DHFR; rs70991108). To assess the associations between blood metabolites (choline, betaine, folate, L-carnitine, o-acetyl-L-carnitine, and trimethylamine N-oxide]), circulating lipids, and fatty liver indices, multiple logistic regression analyses were performed. Overweight/obese participants had 5.8% higher choline (p < 0.05) and 10% higher L-carnitine (p < 0.001) levels than normal-weight subjects. Serum folate and betaine levels were associated with lower total cholesterol (p < 0.001 and p < 0.05), low-density lipoprotein (LDL) cholesterol (p < 0.001 and p < 0.05, respectively), triacylglycerols (p < 0.01 and p < 0.001), and triglyceride glucose index (p < 0.001 and p < 0.01, respectively), though only in overweight/obese people. The PEMT rs12325817 CC genotype was associated with higher levels of high-density lipoprotein (HDL) cholesterol (p < 0.01) in overweight/obese people. The associations between OCM markers, fatty liver indices, and blood lipids differ in subjects with normal and excessive body weight.

The increased intrathecal expression of the monocyte-attracting chemokines CCL7 and CXCL12 in tick-borne encephalitis.

Tick-borne encephalitis (TBE) is a relatively severe and clinically variable central nervous system (CNS) disease with a significant contribution of a secondary immunopathology. Monocytes/macrophages play an important role in the CNS inflammation, but their pathogenetic role and migration mechanisms in flavivirus encephalitis in humans are not well known. We have retrospectively analyzed blood and cerebrospinal fluid (CSF) monocyte counts in 240 patients with TBE presenting as meningitis (n = 110), meningoencephalitis (n = 114), or meningoencephalomyelitis (n = 16), searching for associations with other laboratory parameters, clinical presentation, and severity. We have measured concentrations of selected monocytes-attracting chemokines (CCL7, CXCL12, CCL20) in serum and CSF of the prospectively recruited patients with TBE (n = 15), with non-TBE aseptic meningitis (n = 6) and in non-infected controls (n = 8). The data were analyzed with non-parametric tests, p < 0.05 considered significant. Monocyte CSF count correlated with other CSF inflammatory parameters, but not with the peripheral monocytosis, consistent with an active recruitment into CNS. The monocyte count did not correlate with a clinical presentation. The median CSF concentration of CCL7 and CXCL12 was increased in TBE, and that of CCL7 was higher in TBE than in non-TBE meningitis. The comparison of serum and CSF concentrations pointed to the intrathecal synthesis of CCL7 and CXCL12, but with no evident concentration gradients toward CSF. In conclusion, the monocytes are recruited into the intrathecal compartment in concert with other leukocyte populations in TBE. CCL7 and CXCL12 have been found upregulated intrathecally but are not likely to be the main monocyte chemoattractants.

Porto-systemic shunt - a rare cause of hyperandrogenism in children. Two case reports and review of literature.

Objectives The main cause of hyperandrogenism in children is congenital adrenal hyperplasia, adrenal and gonadal tumors, polycystic ovary syndrome (PCOs) and Cushing's disease. In the last 20 years several descriptions of girls with hyperandrogenism and venous porto-systemic shunts appeared in literature. Case presentation First case is an eleven and a half-year-old girl, was admitted to Department of Endocrinology because of symptoms of hyperandrogenism. Laboratory tests revealed high serum testosterone, androstenedione, and dehydroepiandrosterone sulfate (DHEAS). The ammonia concentration was also increased. In the abdominal angio-CT scans persistent umbilical vein which connected portal and femoral vein was found. The second case was a seven-year-old boy with symptoms of precocious puberty. Blood tests also revealed high concentration of testosterone, androstenedione, DHEAS and ammonia. Imaging studies showed persistent ductus venosus. Conclusion Although pathophysiological relation is not clear, porto-systemic shunts should be considered as a cause of hyperandrogenism of unknown origin in children.

Assessment of Anaplasma phagocytophilum presence in early Lyme borreliosis manifested by erythema migrans skin lesions.

BACKGROUND: To investigate to what extent early Lyme borreliosis patients with erythema migrans are infected with Anaplasma phagocytophilum. METHODS: Three hundred ten patients from Poland with erythema migrans were included in the study. One hundred and eighty-three patients (59%) agreed to have both skin biopsy and blood samples analysed for Borrelia burgdorferi, A. phagocytophilum and 'Candidatus Neoehrlichia mikurensis', with PCR. Positive samples were confirmed with sequencing. RESULTS: B. burgdorferi DNA was detected in 49.7% of the skin samples and in 1.1% of the blood samples. A. phagocytophilum DNA was found in 7.1% blood samples, and in 8.2% of the skin biopsies. In four patients, A. phagocytophilum DNA was detected only in blood; in one case A. phagocytophilum DNA was found simultaneously in blood and skin, and additionally in this patients' blood Borrelia DNA was detected. In four skin samples B. burgdorferi DNA was detected simultaneously with A. phagocytophilum DNA, indicative of a co-infection. CONCLUSIONS: A. phagocytophilum may be present in early Lyme borreliosis characterized by erythema migrans and should always be considered as a differential diagnostic following a tick bite and considered in treatment schemes, as these differs (in early stage of Lyme borreliosis doxycycline, amoxicillin, cefuroxime axetil and azithromycin are recommended, while in anaplasmosis the most effective courses of treatment are doxycycline, rifampin and levofloxacin). Consequently, the role of A. phagocytophilum in erythema migrans should be further studied.

Associations between folate and choline intake, homocysteine metabolism, and genetic polymorphism of MTHFR, BHMT and PEMT in healthy pregnant Polish women.

AIM: Physiological homocysteine (Hcy) concentrations depend on several factors, both dietary (including folate and choline intake) and biological (such as polymorphism of the genes involved in Hcy metabolism). This study aimed to thus test the associations between genes functionally linked with Hcy metabolism (MTHFR, BHMT and PEMT), folate and choline intakes, and total Hcy (tHcy) concentrations of healthy pregnant women. METHODS: One hundred and three healthy Polish women aged 18-44 years, in the third trimester of pregnancy, were enrolled. RESULTS: Mean blood tHcy and glutathione (GSH) concentrations were 8.08 ± 3.25 µM and 4.84 ± 1.21 µM, respectively. Concentrations of tHcy were found to be lower in the women who were taking folic acid supplements than in those who did not take these supplements (7.42 ± 1.78 µM vs 9.28 ± 4.42 µM, P < 0.05). There were no associations found between the examined parameters and BHMT (rs7356530), MTHFR (rs1801133) and PEMT (rs12325817) alone. However, blood tHcy concentrations differed in the PEMT genotype subgroups when choline and folate intakes were considered: respectively, 25% and 20% lower levels were observed in the C allele carriers who met their needs of choline or folate than in those who did not take enough these nutrients (P < 0.05 for both associations). CONCLUSIONS: This study suggests that choline and folate intakes might interact with MTHFR, BHMT and PEMT polymorphisms to determine tHcy and GSH blood concentrations in healthy pregnant women.

Acrodermatitis chronica atrophicans: various faces of the late form of Lyme borreliosis.

INTRODUCTION: Acrodermatitis chronica atrophicans (ACA) is probably the most common late and chronic manifestation of the Lyme borreliosis seen in European patients. AIM: To analyze epidemiological data, and to investigate the effects of treatment of patients with ACA. MATERIAL AND METHODS: Nine patients were included in the study. All patients had serological examinations (ELISA and Western blot) and histopathological examination of the skin lesions performed. Eight patients had PCR in the skin biopsy performed. RESULTS: The duration of symptoms ranged from 2 months to 2 years. In 7 patients, skin lesions were located on lower limbs, in 2 patients - in a non-typical body area - abdomen. In 1 patient, scleroderma and in 3 patients, diabetes mellitus was diagnosed. Borrelia burgdorferi DNA was detected in 25% of the skin biopsy specimens. IgG anti-B. burgdorferi specific antibodies were present in serum of all patients (confirmed by Western blot). In all cases, the diagnosis was confirmed by histopathological examination. The response to ceftriaxone therapy varied. In 5 cases, the lesions resolved completely, in others they faded. CONCLUSIONS: Despite raising awareness of Lyme borreliosis, late forms of the disease such as ACA are still observed. Acrodermatitis chronica atrophicans skin lesions may be located in non-characteristic areas, e.g. abdominal skin. Symptoms are not irritating or painful, therefore patients do not seek medical help. The effect of antibiotic treatment varies.

PEMT rs12325817 and PCYT1A rs7639752 polymorphisms are associated with betaine but not choline concentrations in pregnant women.

Maternal metabolism during gestation may depend on nutrient intake but also on polymorphism of genes encoding enzymes involved in metabolism of different nutrients. Data on choline or carnitine metabolism in pregnant women are scarce. We hypothesized that (1) choline intake in Polish pregnant women is inadequate and (2) choline and carnitine metabolism would differ by genotype and nutritional status of pregnant women. One hundred three healthy Polish women aged 18 to 44 years in the third trimester of pregnancy were enrolled in the study. The average choline, folate, and carnitine intakes were 365 ± 14 mg/d, 1089 ± 859 µg, and 132 ± 8 mg/d, respectively. Most women did not achieve an adequate intake of choline. Average choline, betaine, trimethylamine oxide, l-carnitine, and acetylcarnitine concentrations were 10.64 ± 3.30 µmol/L, 14.43 ± 4.01 µmol/L, 2.01 ± 1.24 µmol/L, 12.73 ± 5.41 µmol/L, and 6.79 ± 3.82 µmol/L, respectively. Approximately 15% lower betaine concentrations were observed in the GG homozygotes of PEMT rs12325817 and in the GG homozygotes of PCYT1A rs7639752 than in the respective minor allele carriers. Birth weight was higher in the G allele homozygotes of the CHDH rs2289205 than in the minor allele carriers: GG: 3398 ± 64 g; GA+AA: 3193 ± 76 g. Our study shows that choline intake in Polish pregnant women is inadequate and that polymorphisms of PEMT rs12325817 and PCYT1A rs7639752 are associated with betaine but not choline concentrations.

Interactions between the growth hormone and cytokines - A review.

Numerous reports on the interactions between the immune and endocrine systems, especially growth hormone axis, can be found in the literature. Growth hormone acts mainly indirectly through insulin-like growth factor-1, which stimulates the growth and development processes, metabolism of lipids, proteins, and carbohydrates, and it also has a modulating effect on the cells of the immune system. Several studies have been conducted on the influence of growth hormone therapy on the immunological parameters in children and adults with and without growth hormone deficiency. However, there have been no definite results and some of them have been even contradictory. Some studies have suggested that administration of growth hormone increases the production of tumor necrosis factor and certain pro- and anti-inflammatory cytokines; whereas other studies have demonstrated the lack of correlation between growth hormone and interleukins. The aim of this paper was to evaluate the available literature on the interaction between growth hormone and TNF-α, pro-inflammatory (IL-1ß, IL-2, IL-6) and anti-inflammatory (IL-4, IL-10) interleukins.

Transgenerational effects of prenatal restricted diet on gene expression and histone modifications in the rat.

Dietary triggers acting on a developing fetus can affect the functioning of the body in later life; this can be observed on various levels, including epigenetic modifications and gene expression. Early-life programmed changes may be transmitted to successive generations. In this study, the impact of prenatal restricted diet was studied in four generations of rats. We hypothesized that this diet can induce changes in the expression of major genes involved in two epigenetic mechanisms: DNA methylation and histone modifications. The transcript level of six genes involved in these processes (Dnmt1, Dnmt3a, Dnmt3b, Mecp2, Hdac1, and Sin3a) was therefore determined in three tissues (liver, adipose, and muscle). This diet was found to have no effect on the F0 pregnant females. In the F1 progeny (fetuses at day 19 of pregnancy and 4-week-old rats) significant differences in the expression of the genes were observed mostly in the liver; in subsequent generations, we therefore studied only this tissue. Among the genes encoding DNA methyltransferases, significant changes were observed for Dnmt1 in the F1 animals from the restricted group, but these were no longer evident in F2 and F3. The Dnmt3a and Dnmt3b genes showed no differences in mRNA level in F1 fetuses. Concerning the transcript level of the Mecp2 gene only in F1 generation significant changes were found. For the histone modification genes, an increase in the expression of Hdac1 in fetus liver was found in F1 and F2, while its level decreased in F3. The abundance of the Sin3a transcript varied in all generations. It was also found that the mRNA levels of the studied genes correlated highly positive with each other, but only in fetuses from the F1 restricted group. The DNA methylation cell potential, defined as the ratio of SAM (S-adenosylmethionine) to SAH (S-adenosylhomocysteine), was measured in the liver, with no alterations being found in the restricted groups. Evaluation of global histone H3 acetylation showed that it underwent a significant increase in the fetal livers of F1, while during aging (four-week old animals) this difference was no longer maintained. A tendency of increased H3 acetylation in fetuses was also detected in F2 generation. In F1 fetuses from restricted group the increased H3 acetylation positively correlated with transcriptional status of the studied genes. Our results indicate that the prenatal restriction diet can affect the activity of genes involved in epigenetic mechanisms in the liver across generations. Moreover, this feeding type influenced the global histone H3 acetylation in fetal liver.