Six weeks of aerobic training improves VO2max and MLSS but does not improve the time to fatigue at the MLSS

The purpose of this study was to investigate the effects of a 6-week aerobic training period on the time to fatigue (t _lim) during exercise performed at the maximal lactate steady state (MLSS). Thirteen untrained male subjects (TG; age 22.5 ± 2.4 years, body mass 72.9 ± 6.7 kg and VO_2max 44.9 ± 4.8 mL kg^?1 min^?1) performed a cycle ergometer test until fatigue at the MLSS power output before and after 6 weeks of aerobic training. A group of eight control subjects (CG; age 25.1 ± 2.4 years, body mass 70.1 ± 9.8 kg and VO_2max 45.2 ± 4.1 mL kg^?1 min^?1) also performed the two tests but did not train during the 6-week period. There were no differences between the groups with respect to the VO_2max or MLSS power output (MLSSw) before the treatment period. The VO_2max and the MLSSw of the TG increased by 11.2 ± 7.2 % (pre-treatment = 44.9 ± 4.8 vs. post-treatment = 49.8 ± 4.5 mL kg^?1 min^?1) and 14.7 ± 8.9 % (pre-treatment = 150 ± 27 vs. post-treatment = 171 ± 26 W), respectively, after 6 weeks of training. The results of the CG were unchanged. There were no differences in t _lim between the groups or within groups before and after training. Six weeks of aerobic training increases MLSSw and VO_2max, but it does not alter the t _lim at the MLSS.     

A Study in First-Episode Psychosis Patients: Does Angiotensin I-Converting Enzyme Activity Associated With Genotype Predict Symptom Severity Reductions After Treatment With Atypical Antipsychotic Risperidone?

BackgroundOur previous studies showed increased angiotensin I-converting enzyme (ACE) activity in chronic schizophrenia patients compared with healthy control (HC) volunteers, and the relevance of combining ACE genotype and activity for predicting schizophrenia was suggested.MethodsACE activity was measured in plasma of ACE insertion/deletion (I/D) genotyped HC volunteers (n = 53) and antipsychotic-naïve first-episode psychosis (FEP) patients (n = 45) assessed at baseline (FEB-B) and also after 2 months (FEP-2M) of treatment with the atypical antipsychotic risperidone.ResultsACE activity measurements showed significant differences among HC, FEP-B, and FEP-2M groups (F = 5.356, df = 2, P = .005) as well as between HC and FEP-2M (post-hoc Tukey’s multiple comparisons test, P = .004). No correlation was observed for ACE activity increases and symptom severity reductions in FEP as assessed by total Positive and Negative Syndrome Scale (r = −0.131, P = .434). FEP subgrouped by ACE I/D genotype showed significant ACE activity increases, mainly in the DD genotype subgroup. No correlation between ACE activity and age was observed in FEP or HC groups separately (r = 0.210, P = .392), but ACE activity level differences observed between these groups were influenced by age.ConclusionsThe importance of measuring the ACE activity in blood plasma, associated with ACE I/D genotyping to support the follow-up of FEP patients, did not show correlation with general symptom amelioration in the present study. However, new insights into the influence of age and I/D genotype for ACE activity changes in FEP individuals upon treatment was demonstrated.     

Wound repair during arm regeneration in the red starfish Echinaster sepositus

Starfish can regenerate entire arms following their loss by both autotomic and traumatic amputation. Although the overall regenerative process has been studied several times in different asteroid species, there is still a considerable gap of knowledge as far as the detailed aspects of the repair phase at tissue and cellular level are concerned, particularly in post‐traumatic regeneration. The present work is focused on the arm regeneration model in the Mediterranean red starfish Echinaster sepositus; to describe the early cellular mechanisms of arm regeneration following traumatic amputation, different microscopy techniques were employed. In E. sepositus, the repair phase was characterized by prompt wound healing by a syncytial network of phagocytes and re‐epithelialisation followed by a localized subepidermal oedematous area formation. Scattered and apparently undifferentiated cells, intermixed with numerous phagocytes, were frequently found in the wound area during these first stages of regeneration and extensive dedifferentiation phenomena were seen at the level of the stump, particularly in the muscle bundles. A true localized blastema did not form. Our results confirm that regeneration in asteroids mainly relies on morphallactic processes, consisting in extensive rearrangement of the existing tissues which contribute to the new tissues through cell dedifferentiation, redifferentiation, and/or migration.     

The efficacy of immediate versus delayed antibiotic administration on bacterial growth and biofilm production of selected strains of uropathogenic Escherichia coli and Pseudomonas aeruginosa

Purpose

The treatment of urinary tract infections (UTI) with antibiotics is commonly used, but recurrence and antibiotic resistance have been growing and concerning clinicians. We studied whether the rapid onset of a protective biofilm may be responsible for the lack of effectiveness of antibiotics against selected bacteria.

Materials and Methods

Two established uropathogenic Escherichia coli strains, UTI89 and CFT073, and two Pseudomonas aeruginosa strains, PA01 and Boston-41501, were studied to establish a reliable biofilm formation process. Bacterial growth (BG) was determined by optical density at 600 nm (OD 600) using a spectrophotometer, while biofilm formation (BF) using crystal violet staining was measured at OD 550. Next, these bacterial strains were treated with clinically relevant antibiotics, ciprofloxacin HCl (200 ng/mL and 2 μg/mL), nitrofurantoin (20 μg/mL and 40 μg/mL) and ampicillin (50 μg/mL) at time points of 0 (T0) or after 6 hours of culture (T6). All measurements, including controls (bacteria -1% DMSO), were done in triplicates and repeated three times for consistency.

Results

The tested antibiotics effectively inhibited both BG and BF when administered at T0 for UPEC strains, but not when the antibiotic administration started 6 hours later. For Pseudomonas strains, only Ciprofloxacin was able to significantly inhibit bacterial growth at T0 but only at the higher concentration of 2 μg/mL for T6.

Conclusion

When established UPEC and Pseudomonas bacteria were allowed to culture for 6 hours before initialization of treatment, the therapeutic effect of selected antibiotics was greatly suppressed when compared to immediate treatment, probably as a result of the protective nature of the biofilm.     

Efficacy and safety of leflunomide and predisposing factors for treatment response in patients with active rheumatoid arthritis: RELIEF 6-month data

OBJECTIVE: The RELIEF investigation was a 48-week, multicenter, international study comprising 2 phases. Results from the first phase, a 24-week open-label cohort study that evaluated the safety and efficacy of leflunomide, as well as predisposing factors to treatment response, are reported here. METHODS: Patients received leflunomide 100 mg once daily for 3 days, followed by 20 mg once daily thereafter. All adverse events were documented. Efficacy variables were the European League Against Rheumatism (EULAR) response criteria using the Disease Activity Score (DAS 28) responder rate and the response rate according to American College of Rheumatology (ACR) criteria. At Week 24, baseline data were analyzed to determine predictive factors for treatment response. RESULTS: A total of 969 patients were entered in the trial. No adverse events that have not previously been seen with leflunomide were reported. Among 968 evaluable patients, 673 (69.6%) completed 24 weeks of treatment and were responders according to DAS 28 response rate, and 587 (60.6%) completed 24 weeks of treatment and were responders according to ACR 20%. Thus, there was a high correlation between the EULAR and ACR criteria in determining treatment response. In addition, 240 (24.8%) patients had a low DAS 28 (< or = 3.2) and 123 (12.7%) patients fulfilled the disease remission criteria (DAS 28 < 2.6) at the end of the study. CONCLUSION: This study demonstrates that leflunomide is well tolerated, with a safety profile similar to that seen previously in Phase III studies, and confirms the efficacy of leflunomide across a range of patient categories.     

The diagnostic yield of colonoscopy in hospitalized patients. An observational multicenter prospective study.

BackgroundColonoscopy demands a considerable amount of resources, and little is known about its diagnostic yield among inpatients.AimsTo assess indications, diagnostic yield and findings of colonoscopy for inpatients, and to identify risk factors for relevant findings and cancer.MethodsMulticentre, prospective, observational study including 12 hospitals. Consecutive adult inpatients undergoing colonoscopy were evaluated from February through November 2019.Results1,302 inpatients underwent colonoscopy. Diagnostic yield for relevant findings and cancer was 586 (45%) and 112 (8.6%), respectively. Adequate colon cleansing was achieved in 896 (68.8%) patients. Split-dose/same-day regimen was adopted in 847 (65%) patients. Factors associated to relevant findings were age ≥70 years (RR 1.32), male gender (RR 1.11), blood loss (RR 1.22) and adequate cleansing (RR 1.63). Age ≥70 years (RR 2.08), no previous colonoscopy (RR 2.69) and split-dose/same-day regimen (RR 1.59) significantly increased cancer detection. Implementing adequate cleansing and split-dose/same-day regimen in all patients would increase the diagnostic yield for any relevant findings and cancer from 43% to 70% and from 6% to 10%, respectively.ConclusionRelevant colorectal diseases and cancer were frequent among inpatients. Factors associated with detection of relevant findings were identified. Adequate colon cleansing and split-dose/same-day regimen significantly increased colonoscopy diagnostic yield.     

Associated changes of lipid peroxidation and transforming growth factor beta1 levels in human colon cancer during tumour progression

BACKGROUND: During neoplastic progression, alterations in transforming growth factor beta1 (TGF-beta1) dependent control of cell growth may be an important mechanism of selective proliferation of transformed cellular clones. Defective regulation of TGF-beta1 receptors has been reported to occur in a number of human malignant tumours while little is known of the actual levels of this growth inhibitory cytokine in cancer. On the basis of the demonstrated ability of major lipid peroxidation products such as 4-hydroxynonenal to modulate TGF-beta1 expression and synthesis, we speculated that decreased lipid oxidation, as frequently observed in neoplastic tissues, would contribute to the selective promotion of tumour growth through decreased expression of the cytokine within the tumour mass. AIMS: To seek a possible association between steady state levels of major aldehydic end products of lipid peroxidation and TGF-beta1 content in human colon cancer at different stages of growth. PATIENTS AND METHODS: Tissue biopsies from 15 adult patients with colon adenocarcinoma of different TNM and G stagings were compared with regard to lipid peroxidation aldehydes and net TGF-beta1 levels. For a more comprehensive analysis, cytokine type I and II receptors were measured in tumour biopsies. In one set of experiments, to support the conclusions, the apoptotic effect of TGF-beta1 was evaluated in a human colon cancer cell line, CaCo-2, retaining receptor changes consistent with those observed in cancer patients. RESULTS: With the exception of two extremely advanced cases (T4/G3) in which tissue levels of lipid peroxidation were within the normal range, 4-hydroxynonenal was significantly decreased in all other cancer specimens. Consistent with lipid peroxidation levels, TGF-beta1 protein was markedly decreased or even negligible compared with the corresponding normal tissue surrounding the tumour in all tested biopsies except for the two T4/G3 colon cancers in which cytokine content was again within the normal range. As regards TGF-beta1 receptors, both in tumour sections and CaCo-2 cells, downregulation was greater for TGF-beta1 receptor I than for receptor II. Of note, in CaCo-2 cells, incubation with appropriate doses of TGF-beta1 led to marked nuclear fragmentation and apoptosis. CONCLUSIONS: Evasion of human colon cancer cells from TGF-beta1 mediated growth inhibition appears to be due not only to downregulation of TGF-beta1 receptors, which is inconsistent and unrelated to cancer development, but also to the constant low concentration of this cytokine in the tumour mass. The associated levels of lipid peroxidation aldehydes, much lower than in control tissue, probably represent a lower stimulus for TGF-beta1 production in the neoplastic area and thus a favourable condition for neoplastic progression.     

Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment

OBJECTIVES:Experimental studies on sepsis have demonstrated that ethyl pyruvate is endowed with antioxidant and anti-inflammatory properties. This study aimed to investigate the effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation in a live Escherichia coli-induced sepsis model in rats.METHODS:Male Wistar rats were administered an intravenous suspension of E. coli bacteria or were subjected to a sham procedure. Three hours after bacterial infusion, the rats were randomized into the following groups: a control group without treatment, a group treated with lactated Ringer''s solution (4 mL/kg, i.v.), and a group treated with lactated Ringer''s solution (4 mL/kg, i.v.) plus ethyl pyruvate (50 mg/kg). At 24 h after bacterial infusion, leukocyte-endothelial interactions were investigated using intravital microscopy, and the expression of P-selectin and intercellular adhesion molecule-1 was evaluated via immunohistochemistry. White blood cell and platelet counts were also determined at baseline and 3 h and 24 h after E. coli inoculation.RESULTS:The non-treated and lactated Ringer''s solution-treated groups exhibited increases in the numbers of rolling leukocytes (∼2.5-fold increase), adherent cells (∼3.0-fold), and migrated cells (∼3.5-fold) compared with the sham group. In contrast, treatment with Ringer''s ethyl pyruvate solution reduced the numbers of rolling, adherent and migrated leukocytes to the levels observed in the sham group. Additionally, the expression of P-selectin and intercellular adhesion molecule-1 was significantly increased on mesenteric microvessels in the non-treated group compared with the sham group (p<0.001). The expression of both adhesion molecules was reduced in the other groups, with ethyl pyruvate being more effective than lactated Ringer''s solution. Infusion of bacteria caused significant leukopenia (3 h), followed by leukocytosis with granulocytosis (24 h). There was also an intense and progressive reduction in the number of platelets. However, no differences were observed after treatment with the different solutions.CONCLUSIONS:The presented data suggest that ethyl pyruvate efficiently reduces the inflammatory response in the mesenteric microcirculation in an experimental model of sepsis induced by live E. coli and is associated, at least in part, with down-regulation of P-selectin and intercellular adhesion molecule-1.