Nitric oxide mediates intestinal hyperaemic responses to intraluminal bile-oleate

It has long been recognized that intestinal blood flow increases at mealtimes. Mesenteric hyperaemia is also evoked by activation of sensory peptidergic nerves. Our studies explored the possible role of endogenous nitric oxide (NO) in the rat intestinal vasodilator response to luminal instillation of an oleic acid plus bile mixture before and after acute intrajejunal instillation of capsaicin and after chronic pretreatment with capsaicin. In anaesthetized rats we measured jejunal blood flow (BF) with an ultrasonic Doppler flowmeter and systemic arterial pressure (AP) with a pressure transducer. Intestinal perfusion with 80 mM oleic acid in bile increased BF by 98±12%. Instillation of 4 mg of capsaicin into the jejunal lumen initially increased BF by 42±9% but was followed by vasoconstriction. Inhibition of NO synthase with 25 mg/kg i.v. N-nitro-L-arginine (L-NNA) decreased BF by 27±5% and increased AP by 37±11%. After treatment with L-NNA and after acute and chronic administration of capsaicin, the bile-oleate-induced maximal increases in BF above control levels were 42±7%, 65±12%, and 58±8%, respectively. The observed inhibitory effect of L-NNA on the intestinal hyperaemic response to the bile-oleate mixture was reversed by pretreatment with L-arginine (100 mg/kg i.V.). In capsaicin pretreated rats the subsequent bile-oleate-induced hyperaemia was reduced in magnitude but the inhibitory effects of L-NNA were proportionately the same as in animals not receiving capsaicin. These findings support the hypothesis that NO is involved with bile-oleate-induced mesenteric hyperaemia.     

Visualisation of the extent of damage in a rat spinal cord injury model using MR microsopy of the water diffusion tensor

Magnetic Resonance Diffusion Tensor Imaging (DTI) of the control and traumatic injured spinal cord of a rat in vitro is reported. Experiments were performed on excised spinal cords from 10 Wistar rats, using a home-built 6.4 T MR microscope. MRI and histopathological results were compared. Presented results show that DTI of the spinal cord, perfused with formalin 10 minutes after the injury, can detect changes in water diffusion in white matter (WM) and in gray matter (GM), in areas extending well beyond the region of direct impact. Histology of neurons of the GM shows changes that can be attributed to ischemia. This is in agreement with the observed decrease of diffusion in the injured regions, which may be attributed to the cytotoxic edema due to ischemia. However, the diffusion changes in highly anisotropic WM seem to be caused by a direct action of mechanical force of impact, which significantly distorts the nerve fibers.     

Exome sequencing reveals a novel COL2A1 mutation implicated in multiple epiphyseal dysplasia

Mutations in the COMP, COL9A1, COL9A2, COL9A3, MATN3, and SLC26A2 genes cause approximately 70% of multiple epiphyseal dysplasia (MED) cases. The genetic changes involved in the etiology of the remaining cases are still unknown, suggesting that other genes contribute to MED development. Our goal was to identify a mutation causing an autosomal dominant form of MED in a large multigenerational family. Initially, we excluded all genes known to be associated with autosomal dominant MED by using microsatellite and SNP markers. Follow‐up with whole‐exome sequencing analysis revealed a mutation c.2032G>A (p.Gly678Arg) in the COL2A1 gene (NCBI Reference Sequence: NM_001844.4), which co‐segregated with the disease phenotype in this family, manifested by severe hip dysplasia and osteoarthritis. One of the affected family members had a double‐layered patella, which is frequently seen in patients with autosomal recessive MED caused by DTDST mutations and sporadically in the dominant form of MED caused by COL9A2 defect.     

Treatment with continuous positive airway pressure may affect blood glucose levels in nondiabetic patients with obstructive sleep apnea syndrome

STUDY OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) is often associated with impaired glucose metabolism. Data on the effects of OSAS treatment with continuous positive airway pressure (CPAP) on blood glucose and insulin resistance are conflicting. The study aimed at assessing the immediate effect of CPAP on glucose control measured with a continuous glucose monitoring system (CGMS). PARTICIPANTS AND MEASUREMENTS: Nine non-diabetes subjects with OSAS (mean age 53.0 +/- 8.0 years; body mass index 34.8 +/- 5.3 kg/m2) underwent 2 overnight polysomnographic examinations: a diagnostic study and one with CPAP treatment. Continuous glucose monitoring system (CGMS) was applied overnight on both occasions. Glucose metabolism was assessed with a 75-g oral glucose tolerance test, plasma insulin and homeostatic model assessment of insulin resistance (HOMA-IR) index. RESULTS: The mean (+/- SD) apnoea-hypopnea index (AHI) at diagnostic polysomnography was 54.3 +/- 29.3 (range 16-81). Fasting plasma insulin levels in patients with OSAS was 84.3 +/- 43.4 pM at baseline, and the HOMA-IR was 3.6 +/- 2.2. CPAP treatment in the subjects with OSAS resulted in a significant reduction in the AHI to 4.5 +/- 7.1. All of the major saturation parameters improved significantly on CPAP. CGMS showed mean glucose values significantly higher during the CPAP night than during the diagnostic night: 80 +/- 11 mg/dL versus 63 +/- 7 mg/dL (P < .01). Fasting insulin and HOMA-IR measured after the CPAP night tended to be higher than at baseline (98.4 +/- 51.0 pmol vs 84.3 +/- 43.4 pmol and 3.9 pmol +/- 2.6 vs 3.6 +/- 2.2 pmol, respectively, P > .05). CONCLUSION: CPAP treatment in nondiabetic obese patients with OSAS may have an immediate elevating effect on blood glucose.     

Mice with mutations in Mahogunin ring finger-1 (Mgrn1) exhibit abnormal patterning of the left-right axis.

Mahogunin Ring Finger 1 (Mgrn1) encodes a RING-containing protein with ubiquitin ligase activity that has been implicated in pigment-type switching. In addition to having dark fur, mice lacking MGRN1 develop adult-onset spongy degeneration of the central nervous system and have reduced embryonic viability. Observation of complete situs inversus in a small proportion of adult Mgrn1 mutant mice suggested that embryonic lethality resulted from congenital heart defects due to defective establishment and/or maintenance of the left-right (LR) axis. Here we report that Mgrn1 is expressed in a pattern consistent with a role in LR patterning during early development and that many Mgrn1 mutant embryos show abnormal expression of asymmetrically expressed genes involved in LR patterning. A range of complex heart defects was observed in 20-25% of mid-to-late gestation Mgrn1 mutant embryos and another 20% were dead. This finding was consistent with 46-60% mortality of mutants by weaning age. Our results indicate that Mgrn1 acts early in the LR signaling cascade and is likely to provide new insight into this developmental process as Nodal expression was uncoupled from expression of other Nodal-responsive genes in Mgrn1 mutant embryos. Our work identifies a novel role for MGRN1 in embryonic patterning and suggests that the ubiquitination of MGRN1 target genes is essential for the proper establishment and/or maintenance of the LR axis.     

A Vicious Cycle of Osteosarcopenia in Inflammatory Bowel Diseases—Aetiology,Clinical Implications and Therapeutic Perspectives

Sarcopenia is a disorder characterized by a loss of muscle mass which leads to the reduction of muscle strength and a decrease in the quality and quantity of muscle. It was previously thought that sarcopenia was specific to ageing. However, sarcopenia may affect patients suffering from chronic diseases throughout their entire lives. A decreased mass of muscle and bone is common among patients with inflammatory bowel disease (IBD). Since sarcopenia and osteoporosis are closely linked, they should be diagnosed as mutual consequences of IBD. Additionally, multidirectional treatment of sarcopenia and osteoporosis including nutrition, physical activity, and pharmacotherapy should include both disorders, referred to as osteosarcopenia.     

How Do Dieticians on Instagram Teach? The Potential of the Kirkpatrick Model in the Evaluation of the Effectiveness of Nutritional Education in Social Media

The growing popularity of health education on social media indicates the need for its appropriate evaluation. This paper aims to present the potential of the Kirkpatrick Model (KM) with New World Kirkpatrick Model (NWKM) additions to evaluate the nutritional education provided by dieticians via Instagram. Instagram profiles of ten dieticians providing nutritional education for their followers were analyzed in March and April 2021. The study sample included profiles of both macro- and micro-influencers. The analyzed quantitative data included Instagram Engagement Rate and the number of likes and comments per post. The qualitative analysis of the comments was performed following the theoretical framework provided by the KM and NWKM. Collected data showed followers’ satisfaction, commitment, and relevance of the presented content, fulfilling the Level 1 of NWKM. Level 2 of NWKM was represented by 4 out of 5 dimensions (knowledge, attitude, confidence, commitment). No comments were found only for skills. Both Levels 3 (Behavior) and 4 (Results) of the KM were met. However, the use of the NWKM for them seems limited. The KM can be used to evaluate nutritional education on social media. The NWKM additions seem applicable mostly for Levels 1 and 2.     

The Association between Nutritional Status and In-Hospital Mortality among Patients with Heart Failure—A Result of the Retrospective Nutritional Status Heart Study 2 (NSHS2)

Background: A nutritional status is related to the prognosis and length of hospitalisation of patients with heart failure (HF). This study aims to assess the effect of nutritional status on in-hospital mortality in patients with heart failure. Methods: We conducted a retrospective study and analysis of medical records of 1056 patients admitted to the cardiology department of the University Clinical Hospital in Wroclaw (Poland). Results: A total of 1056 individuals were included in the analysis. A total of 5.5% of patients died during an in-hospital stay. It was found that in the sample group, 25% of patients who died had a BMI (body mass index) within the normal range, 6% were underweight, 47% were overweight, and 22% were obese. Our results show that non-survivors have a significantly higher nutrition risk screening (NRS) ≥3 (21% vs. 3%; p < 0.001); NYHA (New York Heart Association) grade 4 (70% vs. 24%; p < 0.001). The risk of death was lower in obese patients (HR = 0.51; p = 0.028) and those with LDL (low-density lipoprotein) levels from 116 to <190 mg/dL (HR = 0.10; p = 0.009, compared to those with LDL <55 mg/dL). The risk of death was higher in those with NRS (nutritional risk score) score ≥3 (HR = 2.31; p = 0.014), HFmrEF fraction (HR = 4.69; p < 0.001), and LDL levels > 190 mg/dL (HR = 3.20; p = 0.038). Conclusion: The malnutrition status correlates with an increased risk of death during hospitalisation. Higher TC (total cholesterol) level were related to a lower risk of death, which may indicate the “lipid paradox”. Higher BMI results were related to a lower risk of death, which may indicate the “obesity paradox”.