Improvement of endothelial function in parallel with the amelioration of dry cough and dyspnea due to interstitial pneumonia by intravenous cyclophosphamide pulse therapy in patients with systemic sclerosis: a preliminary report of two cases

Intravenous cyclophosphamide pulse therapy (IVCY) exerts its efficacy against interstitial lung disease (ILD) associated with systemic sclerosis (SSc) by restoring vascular injuries as well as aberrant immune activation. We recently experienced two patients with SSc-ILD in whom the values of brachial flow-mediated dilation (FMD) reflected the efficacy of IVCY. We herein report the details of these cases and discuss the potential of FMD to predict and evaluate the effect of IVCY on SSc-ILD.     

Magnetic resonance imaging (MRI) detection of synovitis and bone lesions of the wrists and finger joints in early-stage rheumatoid arthritis: comparison of the accuracy of plain MRI-based findings and gadolinium-diethylenetriamine pentaacetic acid-enhanced MRI-based findings

Objective

To explore whether synovitis and bone lesions in the wrists and finger joints visualized by plain magnetic resonance imaging (MRI)-based findings correspond exactly or not to those judged by gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced MRI-based findings.

Methods

Magnetic resonance imaging of the wrists and finger joints of both hands were examined in 51 early-stage rheumatoid arthritis (RA) patients whose median disease duration from the onset of articular manifestations to entry was 5?months, by both plain (T1 and short-time inversion recovery images) and Gd-DTPA-enhanced MRI (post-contrast fat-suppressed T1-weighted images) simultaneously. We focused on 15 sites per hand, to examine the presence of synovitis and bone lesions (bone edema and bone erosion). Gd-DTPA-enhanced MRI-based findings were considered “true” lesions, and we evaluated the accuracy of plain MRI-based findings in comparison to Gd-DTPA-enhanced MRI-based findings.

Results

Synovitis, judged by plain MRI-based findings, appeared as false-positive at pretty frequency; thus, the specificity, positive predictive value and accuracy of the findings were low. The rate of enhancement (E-rate) in false-positive synovitis sites was significantly low compared with true-positive synovitis sites where Gd-DTPA enhancement appears. In contrast to synovitis, the false-positivity of bone lesions, judged by plain MRI-based findings, was very low compared with Gd-DTPA-enhanced MRI-based findings.

Conclusion

Synovitis judged by plain MRI-based findings is sometimes considered false-positive especially in sites where synovitis is mild. However, plain MRI is effective in identifying bone lesions in the wrist and finger joints in early-stage RA.     

Adult umbilical hernia with vertical dislocation

We present a case of adult umbilical hernia with vertical dislocation along the abdominal wall. The hernial sac arose from the internal ring and connected to the umbilicus 20?mm below the internal ring. The postoperative course was uneventful. Two years and four months after the operation there was no evidence of recurrent hernia even when abdominal pressure was increased, and the umbilicus looked acceptable. An umbilical hernia is usually within the umbilicus. The hernial sac arose from the internal ring so should be called an umbilical hernia not an epigastric hernia. It is unusual that the umbilical hernia dislocates vertically along the abdominal wall, while the umbilicus stays depressed. This atypical form of umbilical hernia has not been described previously as far as we know.     

Rare case of a rudimentary medial metatarsal non-ossified structure

A 9-year-old boy presented with a rudimentary medial metatarsal non-ossified structure. We considered his condition to be classified as hypoplastic medial member type in the metatarsal type of medial ray polydactyly. When it was considered as polydactyly, it had the longest delay of ossification among reported cases.     

Differences in vertebral,tibial, and iliac cancellous bone metabolism in ovariectomized rats

Bone histomorphometry is usually performed on the iliac bone in humans and the tibia or vertebrae in rats. Bone metabolism differences among skeletal sites may be problematic when translating experimental results from rats to humans, but data on such differences in rats are lacking. Therefore, we examined the differences in bone structure and metabolism among skeletal sites using the lumbar vertebra (LV), tibia, and iliac bone obtained from ovariectomized or sham-operated rats preoperatively and at various times from 3 days to 26 weeks postoperatively. The trabeculae were thicker in the LV, where bone metabolism was less active than at other sites, and numerous fine trabeculae were observed in the tibia, where bone metabolism was more active. The iliac bone structure and metabolism were intermediate between those of the tibia and LV. Ovariectomy induced lower bone volume and higher bone metabolism in all skeletal sites, but the changes were greatest and occurred earliest in the tibia, followed by the iliac bone and then LV. Ovariectomy caused changes in bone metabolic markers, which occurred earlier than those in bone tissue. Activation frequency (Ac.f) increased after ovariectomy. At week 26 in ovariectomized rats, Ac.f was highest in the tibia (3.13 N/year) but similar between iliac bone (0.87 N/year) and LV (1.39 N/year). Ac.f is reportedly 0.3–0.4 N/year in the iliac bone of postmenopausal women, suggesting that bone turnover in rats is several times higher than in humans. The reference values reported here are useful for translating experimental results from rats to humans.     

Combination Metabolomics Approach for Identifying Endogenous Substrates of Carnitine/Organic Cation Transporter OCTN1

Purpose

Solute carrier SLC22A4 encodes the carnitine/organic cation transporter OCTN1 and is associated with inflammatory bowel disease, although little is known about how this gene is linked to pathogenesis. The aim of the present study was to identify endogenous substrates that are associated with gastrointestinal inflammation.

Methods

HEK293/OCTN1 and mock cells were incubated with colon extracts isolated from dextran sodium sulfate-induced colitis mice; the subsequent cell lysates were mixed with the amino group selective reagent 3-aminopyridyl-N-hydroxysuccinimidyl carbamate (APDS), to selectively label OCTN1 substrates. Precursor ion scanning against the fragment ion of APDS was then used to identify candidate OCTN1 substrates.

Results

Over 10,000 peaks were detected by precursor ion scanning; m/z 342 had a higher signal in HEK293/OCTN1 compared to mock cells. This peak was detected as a divalent ion that contained four APDS-derived fragments and was identified as spermine. Spermine concentration in peripheral blood mononuclear cells from octn1 gene knockout mice (octn1^?/?) was significantly lower than in wild-type mice. Lipopolysaccharide-induced gene expression of inflammatory cytokines in peritoneal macrophages from octn1^?/? mice was lower than in wild-type mice.

Conclusions

The combination metabolomics approach can provide a novel tool to identify endogenous substrates of OCTN1.

     

Synthesis,biological evaluation and in silico molecular docking of novel 1-hydroxy-naphthyl substituted heterocycles

The versatile precursor 2-acetyl-4-allyl-1-hydroxy naphthalene was synthesized efficiently via Claisen rearrangement 2-acetyl-1-allyloxynaphthalene. The Claisen-Schmidt condensation of latter precursor afforded the corresponding chalcones which were exploited to synthesize a series of potential heterocycles such as pyrazoline, isoxazoline, benzocoumarin and benzoflavone. The synthesized products showed potent antioxidant and antimicrobial activities. Chalcone 3c, naphthyl pyrazoline 6b and hydroxycoumarin 13 exhibited the highest activity as antioxidants. Their binding mode showed specialized recognition of hydroxycoumarin 13 with the triad key amino acids at the active site of the oxidoreductase enzyme (PDB code 1DXO). 1-Hydroxynaphth-2-yl pyrazoline (6b) revealed the highest efficacy against both Gram positive and negative bacterial species. In silico molecular docking of pyrazoline 6b endorsed its proper binding at the active site of the 2EX6 enzyme which explains its potent antibacterial activity in comparison with standard ampicillin.