Transfusion-related acute lung injury induced by human leucocyte antigen-II antibodies: Analysis of antibody typing and source.

BACKGROUND AND OBJECTIVES: To explore transfusion-related acute lung injury (TRALI) induced by human leucocyte antigen (HLA)-II antibodies, and to analyse antibody typing and source. MATERIALS AND METHODS: We retrospectively analysed the clinical symptoms and signs of two leukaemia patients with suspected TRALI from the same female donor. HLA phenotyping was performed on the two patients, the platelet donor, her husband and her two children. The HLA and human neutrophil antigen antibodies in the donor's plasma were identified. RESULTS: The clinical manifestations of two leukaemia patients were those of TRALI, and we treated them with timely ventilator support. A high titre of HLA-II antibodies was in the plasma of the platelet donor. The antibodies were directed at HLA-DRB3*03:01, HLA-DRB1*09:01, HLA-DRB1*12:02, HLA-DRB3*01:01 and HLA-DRB1*12:01:01G, which were specific to the HLA antigens of the two patients. High-resolution HLA genotyping suggested that the donor's HLA-II antibodies were derived from immune stimulation by the husband's antigens during pregnancy. CONCLUSIONS: This study described two cases of TRALI caused by HLA-II antibodies from the same female donor. Appropriate management of blood donors with a history of multiple pregnancies is crucial.

Identification of ligustrazine-based analogs of piperlongumine as potential anti-ischemic stroke agents.

Piper longum has a specific aroma and spicy taste. In addition to edible value, current studies have shown that piper longum also has pharmacological activities such as anti-platelet aggregation, anti-inflammation, anti-cancer, anti-diabetes and anti-depression. Piperlongumine is an alkaloid isolated from Piper longum. Based on our previous studies, four Piperlongumine analogs were synthesized, and their anti-platelet aggregation activities were evaluated. Among them, compound 8 has the strongest anti-platelet aggregation activity. Therefore, compound 8 was docked with stroke-related protein targets, and it was found that compound 8 had good binding affinity to MRTF-A complex and Bcl-2. Through animal experiments, it was found that compound 8 could significantly improve the pathological damage of brain tissue after ischemia and could increase the expression of MRTF-A and Bcl-2 in cerebral cortex in rats. These results suggest that compound 8 may have a good inhibitory effect on apoptosis and tissue structurel disorders induced by cerebral ischemia-reperfusion, so as to reduce the injury caused by ischemic stroke.

Effects of school-based high-intensity interval training on body composition, cardiorespiratory fitness and cardiometabolic markers in adolescent boys with obesity: a randomized controlled trial.

BACKGROUND: With accumulating evidence suggesting that CVD has its origins in childhood obesity. The purpose of this study was to determine the effect of a real-world school-based high-intensity interval training intervention on body composition, cardiorespiratory fitness and cardiometabolic markers in obese boys aged 10 to 13 years. METHODS: Forty-five adolescent boys with obesity (age = 11.2 ± 0.7 years, BMI = 24.2 ± 1.0 kg/m2), were randomized to high-intensity interval training group (HIIT, n = 15), moderate-intensity continuous training group (MICT, n = 15), or a control group (CON, n = 15). The intervention groups performed three weekly exercise sessions over 12 weeks. HIIT group performed two sets of eight bouts of 15 s run at high-intensity [90 ~ 100% maximal aerobic speed (MAS)] separated by eight bouts of 15 s recovery run at low-intensity (50% MAS), MICT group performed 30 min run at moderate intensity (60 ~ 70% MAS) and CON group were instructed to continue their normal behaviors. All participants had indices of body composition, cardiorespiratory fitness (CRF) and cardiometabolic markers measured at baseline and post-intervention. Statistical differences between and within groups were determined by use of two-way analysis of variance (ANOVA) with repeated measures. RESULTS: Following the school-based training program, BMI and body fat mass decreased (BMI: - 1.8 kg/m2 vs. - 1.2 kg/m2, P < 0.01; FM: - 1.6 kg, P < 0.05 vs. -3.7 kg, P < 0.01) in HIIT and MICT group, but there was no significant difference between the two interventions; [Formula: see text] both increased significantly in two intervention groups, and the increment of HIIT group was significantly greater than that of MICT (6.1 mL/kg/min vs. 3.8 mL/kg/min, P < 0.01), Visceral adipose tissue was significant decrease in HIIT group (- 53 g vs. -17 g, P < 0.01) whilst the MICT group experienced a significant decrease in body fat percentage (- 3.1 ± 1.0 kg, P < 0.01), but there were no significant difference between the two interventions. Low-density lipoprotein cholesterol decreased only in HIIT group (- 17.2%, P < 0.05). Significant decrease in the usual index of insulin resistance (HOMA-IR) occurred in HIIT and MICT groups (- 27.3 and - 28.6%, respectively; P < 0.05). CONCLUSIONS: Our results demonstrated that high-intensity interval training based on running can be used to improve the physical health of obese adolescents in school. Further investigations involving a larger cohort of participants, taken from different schools, is recommended. TRIAL REGISTRATION: title Effect of High Intensity Interval Training on Obese Children and Adolescents, time 16/12/2017, ID ChiCTR-IOR-17013992 , website http://www.chictr.org.cn.

Resveratrol attenuates morphine antinociceptive tolerance via SIRT1 regulation in the rat spinal cord.

In recent years, researchers have begun to pay more attention to the role of Sirtuin 1 (SIRT1, a class III histone deacetylase) in pain. However, little research has been conducted examining the involvement of SIRT1 in chronic morphine tolerance. The aim of this study was to investigate the role of spinal SIRT1 and acetyl-histone H3(Ac-H3) in chronic morphine tolerance in rats. Chronic morphine tolerance was induced by twice-daily intrathecal (i.t.) injections of morphine (10µg) for 6 days. Control rats received normal saline (NS). Resveratrol (Res, a SIRT1 stimulant, 30µg i.t.) or dimethyl sulfoxide (DMSO, 10µl i.t.) was then injected on days 7-13. The thermal paw withdrawal threshold was assessed to determine the analgesic effects of morphine (10µg). qRT-PCR, western blotting and immunohistochemistry were used to detect the expression of SIRT1 and global Ac-H3. Administration of morphine for 6 days induced a stabilized antinociceptive tolerance, down-regulated SIRT1 expression and up-regulated Ac-H3 expression in the spinal dorsal horn. Resveratrol treatment from day 7 to 13 increased SIRT1 expression, suppressed global Ac-H3 expression compared to the morphine tolerance (MT) group, and significantly reversed morphine antinociceptive tolerance. These results suggest that resveratrol reversed morphine tolerance by upregulating the expression of SIRT1 in the spinal dorsal horn. SIRT1 and global Ac-H3 in the spinal cord may play an important role in the mechanisms of chronic morphine tolerance.

Fas and FasL expression in the spinal cord following cord hemisection in the monkey.

The changes of endogenous Fas/FasL in injured spinal cord, mostly in primates, are not well known. In this study, we investigated the temporal changes in the expression of Fas and FasL and explored their possible roles in the ventral horn of the spinal cord and associated precentral gyrus following T(11) spinal cord hemisection in the adult rhesus monkey. A significant functional improvement was seen with the time going on in monkeys subjected to cord hemisection. Apoptotic cells were also seen in the ventral horn of injured spinal cord with TUNEL staining, and a marked increase presents at 7 days post operation (dpo). Simultaneously, the number of Fas and FasL immunoreactive neurons in the spinal cords caudal and rostral to injury site and their intracellular optical density (OD) in the ipsilateral side of injury site at 7 dpo increased significantly more than that of control group and contralateral sides. This was followed by a decrease and returned to normal level at 60 dpo. No positive neurons were observed in precentral gyrus. The present results may provide some insights to understand the role of Fas/FasL in the spinal cord but not motor cortex with neuronal apoptosis and neuroplasticity in monkeys subjected to hemisection spinal cord injury.

Myosin heavy chain isoform profiles remain altered at 7 months if the lacerated medial gastrocnemius is poorly reinnervated: a study in rabbits.

Lacerated skeletal muscles often do not recover full function after repair. Denervated muscles with altered myosin heavy chain isoform (MHC) profiles are known to result in functional impairment. We studied the functional recovery of lacerated muscles, assessing MHC profile changes in association to the involvement of the intramuscular nerve (IM). We tested three lacerated models using the rabbit's medial gastrocnemius where the IM was either cut (NNR), repaired (NR), or preserved intact (NP). Muscles were assessed 7 months after repair for muscle atrophy, isometric contraction (by electrical stimulation), and fibrosis formation at the lesion site. Changes in myofibrillar actomyosin adenosine triphosphatase activity, MHC profile, regenerating myofibers and reinnervation were assessed by Western blot, histology, or immunohistology. Lacerated muscles with a repaired (NR) or an intact (NP) IM showed good recovery, with no significant changes in the MHC profile. Muscles where the IM was not repaired (NNR) resulted in significant scar area at the lesion site (p < 0.05), muscle atrophy (67%, p < 0.05) and loss in contractile properties (63% of the uninjured side, p < 0.05). At 7 months, all muscles were reinnervated. However, the NNR had an inappropriate (polyneural) and poorly distributed reinnervation, the presence of regenerating myofibers, and demonstrated a fast-to-slow MHC transition (71%:29% to 44%:56%, ANOVA, p = 0.018). This was associated to the cut IM when the NNR muscle was lacerated. Poor reinnervation in lacerated skeletal muscles alters the myosin heavy chain profile permanently. This study provides a rationale to also consider biological solutions to improve nerve regeneration and reinnervation in the surgical repair of lacerated muscles.

Unconfined compression properties of a porous poly(vinyl alcohol)-chitosan-based hydrogel after hydration.

A poly(vinyl alcohol) (PVA) hydrogel composite scaffold containing N,O-carboxymethylated chitosan (NOCC) was tested to assess its potential as a scaffold for cartilage tissue engineering in a weight-bearing environment. The mechanical properties under unconfined compression for different hydration periods were investigated. The effect of supplementing PVA with NOCC (20wt.% PVA:5vol.% NOCC) produced a porosity of 43.3% and this was compared against a non-porous PVA hydrogel (20g PVA: 100ml of water, control). Under non-hydrated conditions, the porous PVA-NOCC hydrogel behaved in a similar way to the control non-porous PVA hydrogel, with similar non-linear stress-strain response under unconfined compression (0-30% strain). After 7days' hydration, the porous hydrogel demonstrated a reduced stiffness (0.002kPa, at 25% strain), resulting in a more linear stiffness relationship over a range of 0-30% strain. Poisson's ratio for the hydrated non-porous and porous hydrogels ranged between 0.73 and 1.18, and 0.76 and 1.33, respectively, suggesting a greater fluid flow when loaded. The stress relaxation function for the porous hydrogel was affected by the hydration period (from 0 to 600s); however the percentage stress relaxation regained by about 95%, after 1200s for all hydration periods assessed. No significant differences were found between the different hydration periods between the porous hydrogels and control. The calculated aggregate modulus, H(A), for the porous hydrogel reduced drastically from 10.99kPa in its non-hydrated state to about 0.001kPa after 7days' hydration, with the calculated shear modulus reducing from 30.92 to 0.14kPa, respectively. The porous PVA-NOCC hydrogel conformed to a biphasic, viscoelastic model, which has the desired properties required for any scaffold in cartilage tissue engineering.

Role of multi-drug resistance-associated protein-1 transporter in statin-induced myopathy.

This study investigated the effects of probenecid to inhibit the multi-drug resistance-associated protein-1 (MRP-1) in mediating the efflux and myotoxicity in rat skeletal muscles, with administration of rosuvastatin. Male Sprague-Dawley rats were administered daily, for 15 days, with either rosuvastatin (50, 100 or 200 mg/kg) or probenecid (100 mg/kg) alone, or with a combination of rosuvastatin (50, 100 or 200 mg/kg) and probenecid (100 mg/kg). Skeletal muscle toxicity was elevated with probenecid administered with 200 mg/kg/day of rosuvastatin, with the elevation of creatine kinase by 12-fold, alanine aminotrasferase by 10-fold and creatinine by 9-fold at day 15, with no adverse effects observed when probenecid was given alone. Mitochondria ultrastructural damage with enlargement, disruption, cristolysis and vaculation was seen in the soleus and plantaris of animals administered with probenecid and high dosages of statin. These muscles were also expressing more succinic dehydrogenase (SDH)-positive and cytochrome oxidase (CyOX)-positive fibers. Although generally well-tolerated, statins produce a variety of adverse skeletal muscle events. Hydrophilic statins, with reduced levels of non-specific passive diffusion rates into extra-hepatic tissues, are still seen to produce myopathy. This highlights the important roles of transport mechanisms in statin transport at the skeletal muscles. Excessive influx, reduced efflux or the combination of the two could result in elevated cellular levels of statins at the skeletal muscles, resulting in toxicity. This study provides preliminary evidence that the MRP-1 transporter and efflux at skeletal muscles possibly play significant roles in statin-induced myopathy.