Effect of a 3-month L-carnitine supplementation and resistance training program on circulating markers and bone mineral density in postmenopausal women: a randomized controlled trial.

BACKGROUND: Higher circulating levels of trimethylamine N-oxide (TMAO), which is a metabolite that can be produced by the gut microbiota from L-carnitine (LC), have been associated with bone mineral density (BMD). Because LC supplementation can improve bone density and microstructural properties in animal models, this study aimed to examine the effects of 12 weeks of LC supplementation on BMD and selected blood markers involved in bone metabolism of postmenopausal women participating in a resistance training (RT) program. METHODS: Twenty-seven postmenopausal women, who had not been treated for osteoporosis, with a total T-score above - 3.0 and no diet differences completed 12 weeks of RT. The participants' diets were supplemented with either 1 g of LC-L-tartrate and 3 g of leucine per day (LC group) or 4 g of leucine per day as a placebo (PLA group), in a double-blind fashion. RESULTS: After the intervention in the LC group, plasma total carnitine and serum decorin levels were higher than the corresponding preintervention values (p = 0.040 and p = 0.042, respectively). Moreover, plasma TMAO and serum SPARC levels were higher in the LC group than the corresponding postintervention values in the PLA group (p < 0.001 and p = 0.030, respectively). No changes in the BMD were observed after 3 months of the intervention. CONCLUSIONS: Twelve weeks of LC supplementation during RT program increased plasma TMAO levels and appeared to affect signaling molecules, as indicated by the increase in the resting SPARC and decorin levels, with no significant modification in the BMD. TRIAL REGISTRATION: Retrospectively registered at the ClinicalTrials.gov (NCT05120011).

Multicopy Suppressor Analysis of Strains Lacking Cytoplasmic Peptidyl-Prolyl cis/trans Isomerases Identifies Three New PPIase Activities in Escherichia coli That Includes the DksA Transcription Factor.

Consistent with a role in catalyzing rate-limiting step of protein folding, removal of genes encoding cytoplasmic protein folding catalysts belonging to the family of peptidyl-prolyl cis/trans isomerases (PPIs) in Escherichia coli confers conditional lethality. To address the molecular basis of the essentiality of PPIs, a multicopy suppressor approach revealed that overexpression of genes encoding chaperones (DnaK/J and GroL/S), transcriptional factors (DksA and SrrA), replication proteins Hda/DiaA, asparatokinase MetL, Cmk and acid resistance regulator (AriR) overcome some defects of Δ6ppi strains. Interestingly, viability of Δ6ppi bacteria requires the presence of transcriptional factors DksA, SrrA, Cmk or Hda. DksA, MetL and Cmk are for the first time shown to exhibit PPIase activity in chymotrypsin-coupled and RNase T1 refolding assays and their overexpression also restores growth of a Δ(dnaK/J/tig) strain, revealing their mechanism of suppression. Mutagenesis of DksA identified that D74, F82 and L84 amino acid residues are critical for its PPIase activity and their replacement abrogated multicopy suppression ability. Mutational studies revealed that DksA-mediated suppression of either Δ6ppi or ΔdnaK/J is abolished if GroL/S and RpoE are limiting, or in the absence of either major porin regulatory sensory kinase EnvZ or RNase H, transporter TatC or LepA GTPase or Pi-signaling regulator PhoU.

Identification of Substrates of Cytoplasmic Peptidyl-Prolyl Cis/Trans Isomerases and Their Collective Essentiality in Escherichia Coli.

Protein folding often requires molecular chaperones and folding catalysts, such as peptidyl-prolyl cis/trans isomerases (PPIs). The Escherichia coli cytoplasm contains six well-known PPIs, although a requirement of their PPIase activity, the identity of their substrates and relative enzymatic contribution is unknown. Thus, strains lacking all periplasmic and one of the cytoplasmic PPIs were constructed. Measurement of their PPIase activity revealed that PpiB is the major source of PPIase activity in the cytoplasm. Furthermore, viable Δ6ppi strains could be constructed only on minimal medium in the temperature range of 30-37 °C, but not on rich medium. To address the molecular basis of essentiality of PPIs, proteins that aggregate in their absence were identified. Next, wild-type and putative active site variants of FkpB, FklB, PpiB and PpiC were purified and in pull-down experiments substrates specific to each of these PPIs identified, revealing an overlap of some substrates. Substrates of PpiC were validated by immunoprecipitations using extracts from wild-type and PpiC-H81A strains carrying a 3xFLAG-tag appended to the C-terminal end of the ppiC gene on the chromosome. Using isothermal titration calorimetry, RpoE, RseA, S2, and AhpC were established as FkpB substrates and PpiC's PPIase activity was shown to be required for interaction with AhpC.

Diagnosis and treatment of obscure small bowel bleedings - analysis of double balloon enteroscopy role in diagnosing and treatment algorythm on basis of own material.

Introduction Obscure gastrointestinal bleeding (OGIB) is defined as a reccurent bleeding to gastrointestinal tract without evaluated origin, despite detiled endoscopic and image diagnostics. Mots common reason of OGIB i small bowel bleeding (SBB). Methodology Retrospective analysis of patients hospitalised in Gastroenterology Department of 7 Szpital Marynarki Wojennej w Gdansku with suspicion of OIGB. Results Double balloon enteroscopy was performed in 31 cases. Origin of bleeding was founded in small bowel in 87% of cases and in 64 % successfull,simultaneous therapeutic procedure was performed. No clinically relevant complications were noticed. Conclusion According to actual diagnostic algorythms of OGIB, double balloon enteroscopy is highly effective also in polish medical care system. This tehnique is a safe and effective tool in diagnostics and treatment of SBB, but its availability is still limited in Poland. Abstrakt.

Multiple Transcriptional Factors Regulate Transcription of the rpoE Gene in Escherichia coli under Different Growth Conditions and When the Lipopolysaccharide Biosynthesis Is Defective.

The RpoE σ factor is essential for the viability of Escherichia coli RpoE regulates extracytoplasmic functions including lipopolysaccharide (LPS) translocation and some of its non-stoichiometric modifications. Transcription of the rpoE gene is positively autoregulated by EσE and by unknown mechanisms that control the expression of its distally located promoter(s). Mapping of 5' ends of rpoE mRNA identified five new transcriptional initiation sites (P1 to P5) located distal to EσE-regulated promoter. These promoters are activated in response to unique signals. Of these P2, P3, and P4 defined major promoters, recognized by RpoN, RpoD, and RpoS σ factors, respectively. Isolation of trans-acting factors, in vitro transcriptional and gel retardation assays revealed that the RpoN-recognized P2 promoter is positively regulated by a QseE/F two-component system and NtrC activator, whereas the RpoD-regulated P3 promoter is positively regulated by a Rcs system in response to defects in LPS core biosynthesis, overproduction of certain lipoproteins, and the global regulator CRP. Strains synthesizing Kdo2-LA LPS caused up to 7-fold increase in the rpoEP3 activity, which was abrogated in Δ(waaC rcsB). Overexpression of a novel 73-nucleotide sRNA rirA (RfaH interacting RNA) generated by the processing of 5' UTR of the waaQ mRNA induces the rpoEP3 promoter activity concomitant with a decrease in LPS content and defects in the O-antigen incorporation. In the presence of RNA polymerase, RirA binds LPS regulator RfaH known to prevent premature transcriptional termination of waaQ and rfb operons. RirA in excess could titrate out RfaH causing LPS defects and the activation of rpoE transcription.

[Efficacy of sulpiride and itopride in the treatment of functional dyspepsia in women with emotional and eating disorders]. / Ocena skutecznosci sulpirydu i itoprydu w leczeniu dyspepsji czynnosciowej u kobiet z zaburzeniami emocji i laknienia.

UNLABELLED: Functional dyspepsia is often accompanied by emotional disturbances, especially in postmenopausal women. Impaired homeostasis of the dopaminergic system maybe one of the common pathogenetic factors. The aim of the study was to assess the effect of drugs which block dopamine D2 receptors on psychosomatic condition in postmenopausal women. MATERIAL AND METHODS: The study was conducted in a group of 60 women, aged 53-61 years, with postprandial distress syndrome (PDS) that met the Rome Criteria III. The severity of dyspeptic symptoms was determined statistically using a 10-point Visual Analogue Scale (VAS). The emotional state was estimated with the Hamilton Anxiety Rating Scale (HARS) and the Beck Depression Inventory (BDI), whereas the body mass index (BMI) was the indicator of the nutritional status. Sulpiride (2 x 50 mg) was administered to 30 women for 16 weeks and itopride (2 x 50 mg) to 30 others. RESULTS: After sulpiride and itopride treatment equal decrease of dyspeptic symptoms was observed, respectively from 9.08 to 4.76 pts and from 9.02 to 4.64 pts. Significant reduction in the level of anxiety (p < 0.001) and depression (p < 0.01) was obtained in both groups, slightly higher after sulpiride. However, no significant change in BMI was found. CONCLUSIONS: Sulpiride and itopride are effective in the treatment of dyspepsia in the form of postprandial distress syndrome. These drugs in the several-month treatment have no significant effect on body weight.