Five-year follow-up after percutaneous balloon mitral valvuloplasty in children and adolescents

Balloon mitral valvuloplasty (BMV) is an effective intervention in patients with symptomatic mitral stenosis. However, the late results of BMV in children and adolescents have not been well studied. The aim of this study was to assess the late functional and morphologic results after BMV in children and adolescents. BMV was performed in 46 children and adolescents (mean age 15.5 +/- 3.2 years, range 7 to 19; 19 males) with rheumatic mitral stenosis. Serial clinical and echocardiographic evaluation was conducted to assess the long-term results of the procedure during a follow-up period of 66 +/- 6 months. The mitral valve score was 6 +/- 2/16. BMV was successful in 45 patients (98%). There was a significant increase of the mean mitral valve area index (MVAI) (0.65 +/- 0.14 vs 1.54 +/- 0.23 cm2/m2, p <0.001) and a significant reduction of the mean transmitral pressure gradient (16.1 +/- 2.9 vs 5.1 +/- 3.1 mm Hg, p <0.001) from pre- to post-BMV, respectively. There was no significant change of MVAI or the pressure gradient during the follow-up compared with immediately after BMV (1.51 +/- 0.31 cm2/m2 and 4.9 +/- 2.5 mm Hg, respectively). No deaths or mitral valve replacement occurred during the follow-up period. Restenosis (loss of >50% of the achieved increase in MVAI) occurred in 3 patients (6.5%). All other patients showed persistent improvement in their New York Heart Association class (< or = II). Thus, the event-free survival with good functional results was encountered in 42 patients (91%) at the end of the follow-up period. The left atrial diameter decreased from 4.6 +/- 0.9 before BMV to 3.7 +/- 0.6 cm at follow-up (p <0.05). It is concluded that BMV has excellent intermediate-term results in children and adolescents with a relatively low mitral valve score.     

Side-to-side nerve bridges reduce muscle atrophy after peripheral nerve injury in a rodent model

Background

Peripheral nerve injury can result in muscle atrophy and long-term disability. We hypothesize that creating a side-to-side bridge to link an injured nerve with a healthy nerve will reduce muscle atrophy and improve muscle function.

Methods

Sprague-Dawley rats were divided into four groups (n = 7 per group). Group 1: transection only—a 10-mm gap was created in the proximal tibial nerve; group 2: transected plus repaired—the transected tibial nerve was repaired; group 3: transected plus repaired plus nerve bridge—transected nerve repaired with a distal nerve bridge between the tibial and peroneal nerves via epineurial windows; and group 4: transected plus nerve bridge—transected tibial nerve left unrepaired and distal bridge added. Gait was assessed every 2 wk. At 90 d the following measures were determined: gastrocnemius mass, muscle and nerve nuclear density, and axonal infiltration into the nerve bridge.

Results

Groups 3 and 4 had greater improvements in walking track recovery than groups 1 and 2. Group 3's gastrocnemius muscles exhibited the least amount of atrophy. Groups 1, 2, and 4 exhibited greater histologic appearance of muscle breakdown compared with group 3 and control muscle. Finally, most bridges in groups 3 and 4 had neuronal sprouting via the epineurial windows.

Conclusions

Our study demonstrated reduced muscle atrophy with a side-to-side nerve bridge in the setting of peripheral nerve injury. These results support the application of novel side-to-side bridges in combination with traditional end-to-end neurorrhaphy to preserve muscle viability after peripheral nerve injuries.     

Calorie restriction promotes remyelination in a Cuprizone-Induced demyelination mouse model of multiple sclerosis

Metabolic Brain Disease - Over the past few decades several attempts have been made to introduce a potential and promising therapy for Multiple sclerosis (MS). Calorie restriction (CR) is a dietary...     

Protective Effects of Cannabis sativa on chemotherapy-induced nausea in a rat: Involvement of CB1 receptors

Cyclophosphamide is an anticancer and immunosuppressive agent used in the treatment of various malignancies but causing gastrointestinal distress. Cannabis sativa and its derivatives have been used for the treatment of human gastrointestinal disorders. A purpose of this study was to investigate the effect of C. sativa on nausea induced by cyclophosphamide in rats. The rats were divided into four groups (eight animals per group): Group 1: Normal control (saline i.p.). Group 2: Rats received cyclophosphamide (200 mg/kg i.p.) 3 consecutive days. Group 3 and 4: Rats received cyclophosphamide (200 mg/kg i.p.) across Days 1–7, and C. sativa (20 and 40 mg/kg s.c.) was administered on cyclophosphamide days 4–7. We examined intake of kaolin, normal food and changes in body weight, as an indicator of the emetic stimulus. Oxidative stress markers, antioxidant enzymes status, serotonin (5-HT), dopamine, noradrenaline and CB1R levels were evaluated in the intestinal homogenate. Moreover, histopathological study was performed. Results showed that C. sativa ameliorates cyclophosphamide-induced emesis by increasing in body weight and normal diet intake with a decrease in kaolin diet intake after 7 days. Moreover, C. sativa significantly decreases (serotonin) 5-HT, dopamine and noradrenaline, as well as decreasing oxidative stress and inflammation. Administration of C. sativa significantly increased the expression of CB1R in intestinal homogenate. Treatment with C. sativa also improved the histological feature of an intestinal tissue. These results suggested that C. sativa possess antiemetic, antioxidant and anti-inflammatory effects in chemotherapy-induced nausea in rats by activating CB1R.     

Influence of chrysin on D-galactose induced-aging in mice: Up regulation of AMP kinase/liver kinase B1/peroxisome proliferator-activated receptor-γ coactivator 1-α signaling pathway

Adenosine monophosphate kinase/liver kinase B1/peroxisome proliferator-activated receptor-γ coactivator 1-α (AMPK/LKB1/PGC1α) pathway has a vital role in regulating age-related diseases. It controls neurogenesis, cell proliferation, axon outgrowth, and cellular energy homeostasis. AMPK pathway also regulates mitochondrial synthesis. The current study evaluated the effect of chrysin on D-galactose (D-gal) induced-aging, neuron degeneration, mitochondrial dysfunction, oxidative stress, and neuroinflammation in mice. The mice were allocated randomly into four groups (10 each group): Group 1: normal control group, Group 2: D-gal group, Groups 3 and 4: chrysin (125 and 250 mg/kg, respectively). Groups 2–4 were injected with D-gal (200 mg/kg/day; s.c) for 8 weeks to induce aging. Groups 3 and 4 were orally gavaged every day concurrent with D-gal. At the end of experiment, behavioral, brain biochemical and histopathological changes were monitored. Chrysin administration elevated discrimination ratio in object recognition, Y Maze percentage alternation, locomotor activity and brain contents of AMPK, LKB1, PGC1α, NAD (P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO-1), nerve growth factor (NGF) (neurotrophin-3; NT-3), and seretonin as well as reduced brain contents of tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), advanced glycation end products (AGEs) and glial fibrillary acidic protein (GFAP) compared to D-gal-treated mice. Chrysin also alleviated cerebral cortex and white matter neurons degeneration. Chrysin protects against neurodegeneration, improves mitochondrial autophagy and biogenesis as well as activates antioxidant genes expression. In addition, chrysin ameliorates neuroinflammation and stimulates the release of NGF and serotonin neurotransmitter. So, chrysin has a neuroprotective effect in D-gal induced-aging in mice.     

Genetic polymorphisms of tumour necrosis factor alpha (TNF‐α) promoter gene and response to TNF‐α inhibitors in Spanish patients with inflammatory bowel disease

Tumour necrosis factor alpha (TNF‐α) has an important role in inflammatory response. Alterations in the regulation of TNF‐α have been implicated in a variety of inflammatory disorders, including Inflammatory bowel disease (IBD). Indeed, a common treatment for IBD is the use of TNF‐α inhibitors. Polymorphisms in the TNF‐α promoter region are known to affect the level of gene expression. Our aim was to investigate the influence of these single nucleotide polymorphisms (SNPs) in TNF‐α promoter gene play in the risk of IBD in a Spanish population and their individual response to anti‐TNF‐α treatment. DNA samples from patients with IBD and controls were screened for TNF‐α ?238G/A (rs361525) and ?308G/A (rs1800629) SNPs by PCR‐SSOP using a microbeads luminex assay and compared with response to TNF‐α inhibitors. There were not statistical differences in ?238G/A and ?308G/A allele and genotype frequencies between patients. However, we found an increased frequency of ?308A allele and ?308GA genotype in these nonresponders patients to TNF‐α inhibitors with respect to responders patients (Pc < 0.05). This ?308GA genotype has been classified as high producer of this cytokine. This fact could actually be interesting to explain the different response of patients with IBD with respect to TNF‐α inhibitors. TNF‐α promoter gene polymorphism does not seem to play a role in IBD susceptibility, but particular TNF‐α genotypes may be involved in the different responses to TNF‐α inhibitor treatment in Spanish patients with IBD.     

Design,synthesis, docking study and anticancer evaluation of new trimethoxyphenyl pyridine derivatives as tubulin inhibitors and apoptosis inducers

Microtubules have become an appealing target for anticancer drug development including mainly colchicine binding site inhibitors (CBSIs). A new series of novel trimethoxypyridine derivatives were designed and synthesized as tubulin targeting agents. In vitro anti-proliferative activities of the tested compounds compared to colchicine against hepatocellular carcinoma (HepG-2), colorectal carcinoma (HCT-116), and breast cancer (MCF-7) was carried out. Most of compounds showed significant cytotoxic activities. Compounds Vb, Vc, Vf, Vj and VI showed superior anti-proliferative activities to colchicine. Where compound VI showed IC₅₀ values of 4.83, 3.25 and 6.11 μM compared to colchicine (7.40, 9.32, 10.41 μM) against HCT 116, HepG-2 and MCF-7, respectively. The enzymatic activity against tubulin enzyme was carried out for the compounds that showed high anti-proliferative activity. Also, compound VI exhibited the highest tubulin polymerization inhibitory effect with an IC₅₀ value of 8.92 nM compared to colchicine (IC₅₀ value = 9.85 nM). Compounds Vb, Vc, Vf, Vj, & VIIIb showed promising activities with IC₅₀ values of 22.41, 17.64, 20.39, 10.75, 31.86 nM, respectively. Cell cycle and apoptosis test for compound VI against HepG-2 cells, indicated that compound VI can arrest cell cycle at G2/M phase, and can cause apoptosis at pre-G1 phase, with high apoptotic effect 18.53%. Molecular docking studies of the designed compounds confirmed the essential hydrogen bonding with CYS241 beside the hydrophobic interaction at the binding site compared to reference compounds which assisted in the prediction of the structure requirements for the detected antitumor activity.

Interaction of compounds VI (IC₅₀ = 8.92 nM) (A) and Vj (IC₅₀ = 10.75 nM) (B) with key amino acids of CBS.