[A cross-sectional study on current status of rare disease related health information based on WeChat official accounts in China].

Objective: To understand the current status of rare disease related health information release in WeChat official accounts in China. Methods: We used a series of key words containing "rare diseases" and the names of the top 30 rare diseases in hospitalizations in China to search WeChat official accounts. Eligible articles were selected by systematic sampling. All including WeChat official accounts and articles were evaluated to extract the basic information. Results: No relevant WeChat official accounts were found for 14 rare diseases (46.67%). Most of the WeChat official accounts (52.17%) were initiated by patients and patient groups. No significant difference was detected in the total number of articles between the official accounts related with Traditional Chinese Medicine (TCM) and non-TCM related ones, however, the frequency of the monthly information release was significantly higher in TCM related official accounts (P<0.001), while the average reading number of articles was significantly higher in non-TCM related official accounts (P<0.001). Nearly 80% of the WeChat official accounts had navigation menu, and the average reading number of official accounts with menus was larger than those without menus. The top three topics were rare disease diagnosis and treatment knowledge (46.00%), public welfare activity for rare diseases (12.81%) and uncorrelated things (8.65%), while the first three leading topics were cutting-edge information, public welfare activity and patient story, respectively. Conclusions: The scale for rare disease related health information release based on WeChat official accounts in China has been basically formed, but it is still in development stage. Many improvements should be made in their coverage of rare diseases, release frequency, topic and form. It is urgent to establish or recreate some high-quality WeChat official accounts in order to provide precise information and effectively facilitate the prevention and treatment of rare diseases.

Betel Nut Chewing Is Associated With Reduced Tacrolimus Concentration in Taiwanese Liver Transplant Recipients.

PURPOSE: Studies have shown that arecoline, the major alkaloid component of betel nuts, alters the activity of enzymes in the cytochrome P450 (CYP-450) family. Tacrolimus, an immunosuppressant that protects against organ rejection in transplant recipients, not only is mainly metabolized by CYP3A enzymes but also has a narrow therapeutic range. We aimed to investigate whether dose-adjusted blood trough levels of tacrolimus differed over time between betel nut-chewing and non-betel nut-chewing liver transplant recipients. METHODS: In this retrospective case-control study, 14 active betel nut-using liver recipients were matched at a 1:2 ratio to 28 non-betel nut-using liver recipients by sex, age, graft source, duration of follow-up after liver transplantation, and estimated glomerular filtration rate. Differences in liver function index, renal function index, and dose-adjusted blood trough levels of tacrolimus over an 18-month period were compared between the 2 groups by using the Generalized Estimating Equation approach. RESULTS: Dose-adjusted blood trough levels of tacrolimus tended to be significantly (P = .04) lower in betel nut chewers (mean = 0.81, medium = 0.7, 95% confidence interval [CI] = 0.73 to 0.90) than in nonchewers (mean = 1.12, medium = 0.88, 95% CI = 1.03 to 1.22) during the 18-month study period. However, there was no significant difference in renal and liver function index between the 2 groups. CONCLUSION: Liver transplant recipients receiving tacrolimus tend to have lower blood trough levels of the drug over time if they chew betel nuts.

A randomized controlled trial of oral melatonin supplementation and breast cancer biomarkers.

We examined compliance with and the effects of melatonin supplementation on breast cancer biomarkers (estradiol, insulin-like growth factor I (IGF-1), insulin-like growth factor-binding protein 3 (IGFBP-3), and the IGF-1/IGFBP-3 ratio) in postmenopausal breast cancer survivors. In a double-blind, placebo-controlled study, postmenopausal women with a prior history of stages 0-III breast cancer who had completed active cancer treatment (including hormonal therapy) were randomly assigned to either 3 mg oral melatonin (n = 48) or placebo daily for 4 months. Plasma samples were collected at baseline and after the completion of the intervention. The primary endpoints were compliance and change in estradiol and IGF-1/IGFBP-3 levels. Ninety-five women were randomized (48 to melatonin and 47 to placebo). Eighty-six women (91%) completed the study and provided pre- and postintervention bloods. Melatonin was well tolerated without any grade 3/4 toxicity and compliance was high (89.5%). Overall, among postmenopausal women with a prior history of breast cancer, a 4-month course of 3 mg melatonin daily did not influence circulating estradiol, IGF-1, or IGFBP-3 levels. Compliance was comparable between the two groups. Short-term melatonin treatment did not influence the estradiol and IGF-1/IGBBP-3 levels. Effects of longer courses of melatonin among premenopausal women are unknown. Low baseline estradiol levels in our study population may have hindered the ability to detect any further estradiol-lowering effects of melatonin.

Chromium supplementation enhances insulin signalling in skeletal muscle of obese KK/HlJ diabetic mice.

AIM: Chromium is an essential nutrient required for glucose and lipid metabolism. Laboratory and clinical evidences indicate that chromium supplementation may improve insulin sensitivity by enhancing intracellular signalling. Considerable evidence suggests that serine phosphorylation of insulin receptor substrate 1 (IRS1) at 307 residue (IRS1-Ser307) inhibits insulin signalling and results in peripheral insulin resistance. Therefore, we investigated whether chromium-associated insulin action was mediated by modulation of IRS1-Ser307 phosphorylation. METHODS: Male KK/HlJ mice (genetically obese and insulin resistant) were supplemented daily with chromium-containing milk powder or placebo for 7 weeks. In analysing functionally characterized insulin resistance, the changes of blood biochemicals, inflammatory factors and insulin signalling molecules in skeletal muscle were analysed. RESULTS: Using KK mice model, we demonstrated that daily supplementation of trivalent chromium-containing milk powder reduced serum levels of glucose, insulin and triglycerides, and improved glucose and insulin tolerance. Mechanistic study showed that chromium supplementation activated postreceptor insulin signalling such as increasing IRS1, IRS1 tyrosine phosphorylation, p85alpha regulatory subunit of phosphatidylinositol 3-kinase and glucose transporter 4 expression, stimulating Akt activity, downregulating c-Jun N-terminal kinase (JNK) activity and decreasing IRS1 ubiquitinization and insulin resistance-associated IRS1 phosphorylation (IRS1-Ser307) in skeletal muscle. In addition, chromium supplementation attenuated pro-inflammatory cytokine expression in both blood circulation and skeletal muscle. CONCLUSION: Our data suggest that chromium-containing milk powder supplementation can provide a beneficial effect in diabetic subjects by enhancing insulin signalling in skeletal muscle. The improvement in insulin signalling by chromium was associated with the decreased IRS1-Ser307 phosphorylation, JNK activity and pro-inflammatory cytokine production.

Effect of hyperbaric oxygen on patients with traumatic brain injury.

Hyperbaric oxygen therapy (HBOT) is the medical therapeutic use of oxygen at a higher atmospheric pressure. The United States Food and Drug Administration have approved several clinical applications for HBOT, but HBOT in traumatic brain injury (TBI) patients has still remained in controversial. The purpose of our study is to evaluate the benefit of HBOT on the prognosis of subacute TBI patients. We prospectively enrolled 44 patients with TBI from November 1, 2004 to October 31, 2005. The study group randomly included 22 patients who received HBOT after the patients' condition stabilization, and the other 22 corresponding condition patients were assigned into the matched control group who were not treated with HBOT. The clinical conditions of the patients were evaluated with the Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS) before and 3 to 6 months after HBOT. The GCS of the HBOT group was improved from 11.1 to 13.5 in average, and from 10.4 to 11.5 (p < 0.05) for control group. Among those patients with GOS = 4 before the HBOT, significant GOS improvement was observed in the HBOT group 6 months after HBOT. Based on this study, HBOT can provide some benefits for the subacute TBI patients with minimal adverse side effects.

Effect of Toosendanin on acetylcholine level of rat brain, a microdialysis study.

The effect of prejunctional blocker Toosendanin (TSN) on acetylcholine (ACh) level in striatum and parietal cortex was investigated by means of method of brain dialysis coupled with microbore high-performance liquid chromatograph (HPLC)-electrochemical detection (ECD) with enzyme immobilized post-column at freely moving rats. The results are as follows: (1) TSN inhibits high K+ (100 mM)-induced ACh release from the mentioned two regions of brain, completely and irreversibly. (2) Before the inhibition, there appears a transient rise of ACh level. (3) This rise of ACh level can be blocked by TTX. (4) Calcium is necessary for the onset of this rise, but not for that of the sustained decrease of ACh level. These results indicate that the effect of TSN on central cholinergic synapses is similar to that of neuromuscular junction, namely, its blocking action is always preceded by a Ca(2+)-dependent facilitatory phase with result of a TSN-induced transient rise of ACh, but the sustained decline and final blockade of ACh release are Ca(2+)-independent.

Vasorelaxing effect in rat thoracic aorta caused by laurotetanine isolated from Litsea cubeba Persoon.

The pharmacological effects of laurotetanine on rat isolated thoracic aorta were examined. The contraction of aortic rings caused by high potassium (60 mM) and cumulative concentrations of calcium (0.03-3 mM) was inhibited by 3-50 microM laurotetanine in a dose-dependent manner with an IC50 value of 19.8 +/- 3.6 microM (n = 6) in a 1 mM Ca2+ medium. The phenylephrine (3 microM)-induced contraction was also inhibited by laurotetranine. Its effect was more marked on the tonic contraction than on the phasic contraction and was not easily washed-out. On addition of laurotetanine during the tonic contraction, relaxation could also be observed. This relaxing effect was not antagonized by indomethacin (20 microM) and was still seen in denuded aorta or in the presence of nifedipine (1 microM). The caffeine (20 mM)-induced contraction was not affected by laurotetanine. cAMP and cGMP levels of aorta were not changed by laurotetanine. It is concluded that laurotetanine relaxed the rat thoracic aorta mainly by suppressing the Ca2+ influx through both voltage- and receptor-operated calcium channels.

Functional expression of a mouse growth hormone receptor cDNA in transfected mouse L cells.

A cDNA encoding a full-length mouse (m) growth hormone receptor (GHR) derived from 3T3 F442A cells was amplified by RT-PCR and cloned into a mammalian expression vector. A mouse L cell line (mGHR1.6), which expresses high levels of full-length mGHR, was established. A mGHR-specific mRNA of approx 2.8 kb was found in these cells. Ligand binding studies showed that mGHR 1.6 cells were capable of binding 125I-hGH with a dissociation constant (Kd) of 2.9 +/- 0.13 nM. Scatchard analysis indicated that mGHR1.6 cells had only a single class of mGHR and possessed approx 128,000 GH specific binding sites per cell. Affinity crosslinking studies showed that the recombinant mGHR possessed an apparent molecular mass of 105 kDa. In addition, mGHR1.6 cells responded to growth hormones (GHs) from several species. Two proteins, pp92 and pp95, were found to be tyrosyl phosphorylated following GH treatment. An hGH antagonist, hGH-G120R, inhibited GH-induced phosphorylation of both pp92 and pp95 in a dose-dependent manner. This cell line may be used as an in vitro model in the studies of GH signal transduction and in the screening of GH analogs for biological activity.

Role of parathyroid hormone in rat remnant kidney ammonium metabolism.

The role of parathyroid hormone (PTH) in ammonium metabolism in the rat remnant kidney was studied by examining the effects of parathyroidectomy (PTx) in rats with intact kidneys and with 5/6 nephrectomy (Nx). PTx in rats with intact kidneys caused a rise in urine pH and a decrease in urinary ammonium excretion without affecting in vitro ammonium production rate or the ammonium content in the cortex. Unexpectedly, the ammonium content in the medulla was markedly reduced by PTx so that the corticomedullary ammonium gradient was inverted. As compared to control rats, rats with 5/6 Nx had a lower urinary ammonium excretion rate, a higher in vitro ammonium production rate, and an increase in ammonium content in both cortex and medulla with reduced corticomedullary ammonium gradient. PTx in rats with 5/6 Nx led to a further decrease in urinary ammonium excretion, attenuated the increase in the in vitro ammonium production rate, and lowered the ammonium content in both cortex and medulla with inverted corticomedullary ammonium gradient. These effects of PTx in Nx rats were corrected by continuous PTH infusion with Alzet minipump. In summary, results from these studies indicate that PTH plays an important role in maintaining the urinary ammonium excretion. In rats with intact kidneys, PTH contributes to urinary ammonium excretion by increasing urinary acidification and medullary ammonium accumulation. In rats with reduced nephron mass, PTH enhances urinary ammonium excretion by stimulating ammonium production and retaining medullary ammonium in the remnant kidney.

Effect of dietary lipids on inotropic responses of isolated rat left atrium: attenuation of maximal responses by an unsaturated fat diet.

The effect of varying the dietary fatty acid composition on inotropic responses to various pharmacological agents was investigated in isolated rat left atrium. Pregnant rats were fed either semisynthetic diets supplemented with coconut oil (saturated fatty acids), sunflower oil (unsaturated) or Purina Rodent Chow. Newborns were exposed through the maternal milk and later fed the same diets throughout adulthood. Sunflower oil caused a significant decrease in the maximal response of adult atria to norepinephrine, epinephrine and isoproterenol compared with the other diets. However, no differences in contractile response to norepinephrine were detected at ages 11 and 30 days, indicating a delayed onset of the response changes. We had previously demonstrated defects in the beta adrenoceptor-adenylate cyclase system in homogenates of atria from adult rats fed sunflower oil that may partly explain the attenuated adrenergic response. Additional inotropic studies were performed to further examine the role of this system. There was no change in the maximal contractile response to agents acting through cyclic AMP [cAMP (adenosine 3',5'-cyclic monophosphate)]-independent mechanisms, calcium and phenylephrine. In contrast, maximal responses to forskolin, 3-isobutyl-1-methylxanthine, and N6,2'-O-dibutyryl cAMP, which act via cAMP-dependent mechanisms, were significantly depressed by dietary sunflower oil. No differences were detected in cAMP hydrolysis by phosphodiesterase. These data are consistent with the hypothesis that alterations in adrenergic responsiveness of rat atria after dietary lipid treatment involve functional changes in the adenylate cyclase pathway distal to the enzyme.