Ghrelin improves cognition via activation of the cAMP- CREB signalling pathway in depressed male C57BL/6J mice.

BACKGROUND: Depression leads to a cognitive decline and decreases in ghrelin are observed in depression. Ghrelin affects the level of Brain-derived nerve growth factor (BDNF) through the cAMP-CREB signalling pathway, and lower BDNF levels lead to cognitive decline. Therefore, it is reasonable to assume that in depression, lower ghrelin causes a decrease in BDNF levels and cognitive decline though the cAMP- CREB signalling pathway. METHODS: A total of 120 C57BL/6J male mice were randomly divided into six groups of 20 mice: non-depression groups (sham group, ghrelin group, and ghrelin + (D-lys3)-GHRP-6 group) and depression groups (depression group, depression + ghrelin group and depression + ghrelin + (D-lys3)-GHRP group). A depression mouse model was established by injecting normal saline, ghrelin or ghrelin + (D-lys3) -GHRP-6 into the lateral ventricle of each group. Cognition, hippocampal long-term potentiation (LTP), ghrelin mRNA and protein level, BDNF level and CREB level in the hippocampus were detected. RESULTS: In the depression mouse model groups, all comparison indexes (cognition and hippocampal levels of LTP, ghrelin mRNA and proteins, and BDNF and CREB) had significant negative changes. In the mice with depression, ghrelin or ghrelin + (D-lys3)-GHRP-6 was injected, and all the comparison indicators showed significant positive changes. Supplementation of ghrelin+(D-lys3))-GHRP-6 resulted in more significant positive changes in all comparison indexes than those of ghrelin alone. CONCLUSIONS: In the depression model, lower ghrelin causes hippocampal BDNF to decrease and results in cognitive decline via the cAMP-CREB signalling pathway.

Circadian rhythm of TSH levels in subjects with Alzheimer's disease (AD).

OBJECTIVES: The circadian rhythm of serum thyroid stimulating hormone (TSH) levels in patients with Alzheimer's disease was measured by means of a case-control study. METHODS: Serum samples from cases and controls were collected continuously for 2 days, and then once every 2 h (even number time-point during the first day and odd number time-point in the second). TSH was detected by radioimmunoassay. RESULTS: AD patients had no significant circadian rhythm in serum TSH levels, whereas normal controls did. In normal controls, serum TSH levels from 19:00 to 20:00 were the lowest (19:00, 3.89 ± 0.97 mIU/L; 20:00, 3.76 ± 0.84 mIU/L) and those in the period 2:00-4:00 were the highest (2:00, 6.15 ± 0.94 mIU/L; 3:00, 6.32 ± 1.04 mIU/L; 4:00, 6.39 ± 1.13 mIU/L; F = 6.762, df = 23, P = 0.002). However, in AD patients, 24-h serum TSH levels were 3.80-4.03 mIU/L (F = 0.897, df = 23, P = 0.996). At the 24 time-points, except for the four time-points from 16:00 to 19:00, TSH levels in AD patients were significantly lower than those in normal controls. CONCLUSIONS: The circadian rhythm of serum TSH levels in AD patients did not appear, and their serum TSH levels were significantly lower than those in normal controls. SIGNIFICANCE: The circadian rhythm in serum TSH levels in AD patients differs greatly from that of the general population.

Neuroprotective effect of mesenchymal stem cell-derived extracellular vesicles on optic nerve injury in chronic ocular hypertension.

Mesenchymal stem cells have neuroprotective effects that limit damage to the retina and photoreceptors, and which may be mediated by extracellular vesicles (or exosomes) released by mesenchymal stem cells. To investigate the neuroprotective effect of extracellular vesicles derived from umbilical cord mesenchymal stem cells on glaucoma, we established rat models of chronic ocular hypertension by injecting conjunctival fibroblasts into the anterior chamber to mimic optic nerve injury caused by glaucoma. One week after injury, extracellular vesicles derived from umbilical cord-derived mesenchymal stem cells were injected into the vitreous cavity. We found that extracellular vesicles derived from mesenchymal stem cells substantially reduced retinal damage, increased the number of retinal ganglion cells, and inhibited the activation of caspase-3. These findings suggest that mesenchymal stem cell-derived extracellular vesicles can help alleviate optic nerve injury caused by chronic ocular hypertension, and this effect is achieved by inhibiting cell apoptosis.

Age and risk for depression among the elderly: a meta-analysis of the published literature.

OBJECTIVE: The goal of this study was to determine the relationship between age and risk for depression among the old and the oldest old. Method MEDLINE, EMBASE, and the Cochrane Library database were used to identify potential studies. The studies were divided into cross-sectional and longitudinal subsets. For each study, the numbers of the total participants, cases (for cross-sectional study), or incident cases (for longitudinal study) of depression in each age group were extracted and entered into Review Manager 4.2 software. Qualitative meta-analyses of cross-sectional studies and of longitudinal studies were performed. For prevalence and incidence rates of depression, odds risk (OR) and relative risk (RR) were calculated, respectively. RESULTS: The qualitative meta-analyses showed that, compared with younger participants (above vs. below 65 years, above vs. below 70 years, above vs. below 75 years, and above vs. below 80 years), older age groups had a significantly higher risk for depression. (All of the ORs and RRs were significant.) Compared with participants aged 55-89, those aged above 90 years had no higher risk for depression. (Neither the OR nor the RR was significant.) CONCLUSIONS: Despite the methodological limitations of this meta-analysis, older age appears to be an important risk factor for depression in the general elderly population (aged below 80 years), but not in the oldest population (aged above 85 years).

Association of serum uric acid with Pro12Ala polymorphism in PPAR-γ2 among Chinese nonagenarians/centenarians.

BACKGROUND AND AIMS: In previous studies, Pro12Ala polymorphism in peroxisome proliferator- activated receptors gamma 2 (PPAR-γ2) was shown to be associated with both longevity and metabolic syndrome, which was closely related with hyperuricemia. We examined long-lived subjects (≥90 years), to ascertain whether the polymorphism is associated with the level of serum uric acid (SUA). METHODS: The present study analysed data from a survey conducted in 2005 on all residents aged 90 years or more in a district with 2,311,709 inhabitants. RESULTS: The sample comprised 669 unrelated Chinese participants (aged 90-108 years, mean: 93.54±3.53 years; 67.2% women). The genotype frequencies of the Pro12Ala polymorphism were 0% Ala12Ala and 9.0% Pro12Ala, 91.0% Pro12Pro. Between men or women, and between subjects who were or were not 12Ala carriers, neither in SUA levels nor the prevalence of hyperuricemia were significant. Between subjects with and without hyperuricemia, the difference in prevalence of 12Ala carriers was also non-significant. Unadjusted and adjusted multiple logistic regressions showed that the odds ratios (OR) for hyperuricemia were not associated with Pro12Ala polymorphism in PPAR-γ2. CONCLUSIONS: In Chinese nonagenarians and centenarians, SUA levels are not associated with polymorphism in PPAR-γ2.

Probiotics for preventing acute upper respiratory tract infections.

BACKGROUND: Probiotics may improve a person's health by regulating their immune function. Some studies show that probiotic strains can prevent respiratory infections. However, no evidence of the benefits of probiotics for acute upper respiratory tract infections (URTIs) and related potential adverse effects has been published. OBJECTIVES: To assess the effectiveness and safety of probiotics for preventing acute URTIs. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (Ovid) (1950 to May week 1, 2011), EMBASE (1974 to May 2011), Web of Science which includes Science Citation Index (from 1900 to May 2011) and Conference Proceedings Citation Index (from 1991 to May 2011), the Chinese Biomedical Literature Database, which includes the China Biological Medicine Database (from 1978 to May 2011), the Chinese Medicine Popular Science Literature Database (from 2000 to May 2011) and the Masters Degree Dissertation of Beijing Union Medical College Database (from 1981 to May 2011). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing probiotics with placebo to prevent acute URTIs. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility, quality of trials and extracted data. MAIN RESULTS: We included 14 RCTs, although we could only extract available data to meta-analyse in 10 trials which involved 3451 participants. We found that probiotics were better than placebo when measuring the number of participants experiencing episodes of acute URTI: at least one episode: odds ratio (OR) 0.58; 95% confidence interval (CI) 0.36 to 0.92; at least three episodes: OR 0.53; 95% CI 0.36 to 0.80; rate ratio of episodes of acute URTI: rate ratio 0.88; 95% CI 0.81 to 0.96; and reduced antibiotic prescription rates for acute URTIs: OR 0.67; 95% CI 0.45 to 0.98. Probiotics and placebo were similar when measuring the mean duration (MD) of an episode of acute URTI: MD -0.29; 95% CI -3.71 to 3.13 and adverse events: OR 0.92; 95% CI 0.37 to 2.28. Side effects of probiotics were minor and gastrointestinal symptoms were the most common. We found that some subgroups had a high level of heterogeneity when conducting pooled analyses. AUTHORS' CONCLUSIONS: Probiotics were better than placebo in reducing the number of participants experiencing episodes of acute URTIs, the rate ratio of episodes of acute URTI and reducing antibiotic use. This indicates that probiotics may be more beneficial than placebo for preventing acute URTIs. However, the results have some limitations and there were no data for older people.

Education programmes for people with diabetic kidney disease.

BACKGROUND: Adherence to complex regimens for patients with diabetic kidney disease (DKD) is often poor. Interventions to enhance adherence require intensive education and behavioural counselling. However, whether the existing evidence is scientifically rigorous and can support recommendations for routine use of educational programmes in DKD is still unknown. OBJECTIVES: To evaluate the benefits and harms of education programmes for people with DKD. SEARCH STRATEGY: In January 2010 we searched the Cochrane Renal Group's Specialised Register, CENTRAL, MEDLINE, EMBASE and four Chinese medicine databases (CBM-disc, Chinese Science and Technique Journals Database, China National Infrastructure and WanFang). SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs studying the benefits and harms of educational programmes for people with DKD. DATA COLLECTION AND ANALYSIS: Two authors independently searched the literature, determined study eligibility, assessed quality, extracted and entered data. We expressed dichotomous outcomes as risk ratios (RR) with 95% confidence intervals (CI) and continuous data as mean difference (MD) or standardised mean differences (SMD). Data were pooled using the random effects model. MAIN RESULTS: Two studies (207 patients) were eligible. The methodological quality was not high. Compared with no educational programmes, educational programmes for patients with diabetes on dialysis improved patients' knowledge for the following outcomes: diagnosis (SMD 1.14, 95% CI 0.93 to 1.90); monitoring (SMD 1.51, 95% CI 1.0 to 2.01); hypoglycaemia (SMD 1.67, 95% CI 1.16 to 2.17), hyperglycaemia (SMD 0.80, 95% CI 0.35 to 1.25); medication with insulin (SMD 1.21, 95% CI 0.74 to 1.68); oral medication (SMD 0.98, 95% CI 0.52 to1.43); personal health habits (SMD 1.84, 95% CI 1.33 to 2.36); diet (SMD 0.53, 95% CI 0.09 to 0.97); exercise (SMD 1.13, 95% CI 0.67 to 1.60); chronic complications (SMD 1.28, 95% CI 0.80 to1.75) and living with diabetes and coping with stress (SMD 0.71, 95% CI 0.26 to 1.15). For patients with diabetes and microalbuminuria, educational programmes improved general knowledge for the following outcomes: diabetes (SMD 0.84, 95% CI 0.43 to 1.26); patients' total self-efficacy (MD 19.00, 95% CI 12.58 to 25.42) and patients' changes in beliefs on treatment effectiveness (MD 0.25, 95% CI 0.07 to 0.43) at the end of treatment, and general knowledge (MD 14.39, 95% CI 7.45 to 21.33); specific self-efficacy in home blood glucose monitoring (HBGM) (MD 11.28, 95% CI 1.92 to 20.64) and changes of beliefs on personal control (MD 0.31, 95% CI 0.01 to 0.61) at the end of three-months follow-up. For patients with diabetes on dialysis, educational programmes also showed improvement in the following self-management behaviours: checking feet (RR 1.63, 95% CI 1.01 to 2.63); using lotion (RR 9.71, 95% CI 2.45 to 38.56) and wearing appropriate shoes and socks (RR 4.39, 95% CI 1.87 to 10.32). For patients with diabetes and microalbuminuria, educational programmes improved the following behaviours: general diet (MD 0.73, 95% CI 0.10 to 1.36), specific diet (MD 1.02, 95% CI 0.42 to1.62) and HBGM (MD 2.13, 95% CI 1.18 to 3.08) at the end of treatment; and specific diet (MD 0.62, 95% CI 0.18 to 1.06) and HBGM (MD 1.48, 95% CI 0.48 to 2.48) at the end of three-months follow-up. No data were available on changes in kidney function, incidence of cardiovascular events, change of patients' attitude or adverse events. AUTHORS' CONCLUSIONS: Education programmes appear to have beneficial effects on improving patients' knowledge of diabetes and some self-management behavioural changes for patients with diabetes on dialysis or with microalbuminuria. Educational programmes appear to have beneficial effects on improving patients' self-efficacy and result in some beliefs changes for patients with diabetes and microalbuminuria. However, only two studies with small sample sizes and inadequate quality were included in this review. There is, therefore, inadequate evidence to support the beneficial effects of education programmes for people with DKD.

Cognitive function and risk for depression in old age: a meta-analysis of published literature.

BACKGROUND: We assessed the relationship between cognitive impairment (including mild cognitive impairment with no signs of dementia, and dementia) and risk for depression in old age (60 years and older). METHODS: MEDLINE, EMBASE and the Cochrane Library database were used to identify potential studies. All of the clinical studies that produced data on the association between cognitive function and risk of depression among individuals aged 55 years or older were identified and included in this review. The studies were classified into cross-sectional and longitudinal subsets. The quantitative meta-analysis of cross-sectional and longitudinal studies were performed. For prevalence and incidence rates of depression, odds risk (OR) and relative risk (RR) were calculated, respectively. RESULTS: Since all but two studies found in the search were for individuals aged 60 years or over, we assessed and reported on results for this larger group only. In this review we included 13 cross-sectional and four prospective longitudinal studies. The quantitative meta-analysis showed that, in old age, individuals with non-dementia cognitive impairment had neither significant higher prevalence nor incidence rates of depression than those without (odds risk (OR): 1.48, 95% confidence intervals (95% CI): 0.87-2.52; relative risk (RR): 1.12, 95% CI: 0.62-2.01). In old age, individuals with dementia had both significant higher prevalence and incidence rates of depression than those without (OR: 1.82, 95% CI: 1.15-2.89; RR: 3.92, 95% CI: 1.93-7.99). CONCLUSIONS: Despite the methodological limitations of this meta-analysis, we found that in old age, there was no association between depression and cognitive impairment with no dementia; however, there was a definite association between depression and dementia and thus dementia might be a risk for depression.

Fibrinogen, fibrin degradation products and risk of sarcopenia.

BACKGROUND & AIMS: Increasing data suggests that chronic low-grade inflammation plays an important role on development of sarcopenia. The present study was designed to identify the association between fibrinogen, fibrin degradation products (FDP) and sarcopenia risk in hospitalized old patients. METHODS: A total of 437 patients were enrolled in this cross-sectional study (148 with sarcopenia and 289 without sarcopenia). Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Body composition, grip strength and gait speed were performed to participants. Fibrinogen, FDP levels were measured. Logistic regression analyses were carried out to assess the association between fibrinogen and sarcopenia, between FDP and sarcopenia, respectively. RESULTS: Compared to non-sarcopenic patients, fibrinogen and FDP levels were found to be higher in the sarcopenic group (3.07 g/L vs 2.79 g/L, 1.75 µg/mL vs 1.00 µg/mL, respectively, p < 0.05). Multiple linear regression analysis showed a significant negative association between fibrinogen and gait speed (ß: -0.164, p = 0.008), and muscle strength (ß: -0.231, p < 0.001). Multivariable logistic regression analysis showed that fibrinogen and FDP were independently associated with sarcopenia (odds ratio 1.32 [95% confidence interval 1.03, 1.70], p = 0.009; odds ratio 1.07 [95% confidence interval 1.01, 1.19], p = 0.049, respectively). ROC curve revealed that the cutoff values of fibrinogen and FDP to predict sarcopenia risk were 2.54 g/L and 1.15 µg/mL, respectively. CONCLUSIONS: In hospitalized old patients, serum fibrinogen and FDP levels are elevated in sarcopenia patients than those without sarcopenia. Fibrinogen and FDP are associated with sarcopenia in a concentration-dependent manner.

Association between body mass index and cognitive function among Chinese nonagenarians/centenarians.

AIMS: We examined the individual association between body mass index (BMI) and cognitive function among the very elderly. METHODS: The present study analyzed data from a survey that was conducted on all residents aged 90 years or more from a district which had 2,311,709 inhabitants in 2005. The subjects were divided into 4 groups according to quartiles of BMI (<16.6, 16.6-18.9, 18.9-21.1 and >21.1), and according to classification criteria of underweight, normal weight, overweight and obesity in BMI (<18.5, 18.5-23.0, 23.0-27.5 and >27.5), respectively. RESULTS: The subjects included in the statistical analysis were 211 men and 427 women. Those in the 3rd quartile of BMI (18.9-21.1) had higher cognitive function scores (p < 0.001) and were less likely to present possible dementia (p = 0.016) than the others. However, there was no difference in cognitive function scores (p = 0.350) or prevalence of possible dementia (p = 0.263) among obesity, overweight, normal weight and underweight groups. CONCLUSIONS: Concerning longevity in Chinese, there is an association between BMI and cognitive function. BMI of around 20 (18.9-21.1) is associated with the lowest risk of prevalence of possible dementia and the highest cognitive function scores.

Relationship between anti-fibrotic effect of Panax notoginseng saponins and serum cytokines in rat hepatic fibrosis.

The aim of this study was to investigate the relationship between anti-fibrotic effect of Panax notoginseng saponins (PNS) and serum cytokines in rat hepatic fibrosis. Hepatic fibrosis induced by carbon tetrachloride (CCl(4)) was studied in animal models using SD rats. Liver index, serum alanine amino transferase (ALT), aspartate amino transferase (AST), transforming growth factor-beta1 (TGF-beta1), tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured, respectively. Liver index and the degree of liver fibrosis were also determined. Our results showed that the levels of ALT, AST and liver index in PNS-treated group were markedly lower than those in model group. PNS therapy also significantly attenuated the degree of hepatic fibrosis, collagen area and collagen area percent in liver tissue. Furthermore, the levels of serum TGF-beta1, TNF-alpha and IL-6 were strikingly reduced in PNS-treated group compared with model group while the production of IL-10 was up-regulated. These findings demonstrate that PNS has certain therapeutic effects on hepatic fibrosis probably by immunoregulating the imbalance between pro-fibrotic and anti-fibrotic cytokines.

Association of cognitive impairment with serum lipid/lipoprotein among Chinese nonagenarians and centenarians.

The association of cognitive impairment with abnormal levels of serum lipid/lipoprotein in the elderly, in whom there are differences between the old aged 65-84 years and the oldest old aged 85 years or above, has been confirmed by previous studies. However, there are no relevant data from a Chinese oldest old population. In the present study, we observed an association of cognitive impairment with abnormal levels of serum lipid/lipoprotein among very old people using a Chinese cohort aged 90-108 years. The population included 709 unrelated Chinese nonagenarians and centenarians (67.8% women, mean age 93.8 years). The mean score of cognitive function (measured with the 30-item Mini-Mental State Examination, MMSE) was 14.9 (SD 6.0). Comparing abnormal with normal levels of serum lipid/lipoprotein (including triglycerides, total cholesterol, high-density lipoprotein and low-density lipoprotein), in both genders, the odds ratio of cognitive impairment was statistically insignificant. There were no significant differences in levels of lipid/lipoprotein between subjects with and without cognitive impairment. Pearson correlation showed that MMSE scores were not significantly correlated with levels of lipid/lipoprotein. In summary, we found that levels of serum lipid/lipoprotein were not directly correlated with cognitive impairment among Chinese nonagenarians and centenarians.

Association of cognitive impairment with smoking, alcohol consumption, tea consumption, and exercise among Chinese nonagenarians/centenarians.

PURPOSE: In the present study, we observed the association of cognitive impairment with current/former habits of smoking, alcohol consumption, tea consumption, and exercise among very old people using a Chinese cohort aged 90 to 108 years. METHODS: A cross-sectional study. RESULTS: The sample included 681 unrelated Chinese nonagenarians/centenarians (67.25% women). In men, compared with subjects without cognitive impairment, those with cognitive impairment had significantly higher prevalence of habits of smoking (P=0.048 and 0.004, for former/current, respectively) and alcohol consumption (P=0.003 and 0.049, for former/current, respectively) but had significantly lower prevalence of habits of tea consumption (P=0.041 and 0.044, for former/current, respectively) and current exercise (P=0.020). Subjects with habits of smoking had significantly lower cognitive function scores than those without these habits (mean difference=1.78 and 1.69, P=0.029 and 0.035, for former/current, respectively), but subjects with habit of current exercise had significantly higher cognitive function scores than those without this habit (mean difference=1.53, P=0.038). However, in women, there were no significant differences in prevalence of these habits between subjects with and without cognitive impairment and also no significant differences in cognitive function scores between subjects with and without these habits. Only current smoking habits in men had a significant odds ratio for cognitive impairment (odds ratio, 2.125; 95% confidence interval, 1.186-3.998). CONCLUSIONS: Among nonagenarians/centenarians, in men, there are associations of cognitive impairment with habits of former/current smoking and current exercise, as well as indefinite associations with habits of alcohol and tea consumption. Smoking may have a significant negative impact on cognitive function, but current exercise significantly improve cognitive function. However, in women, there are no associations of cognitive impairment with all the habits.

[Study on the change of myocardial cell and matrix in the rats with insulin resistance and type 2 diabetes mellitus].

OBJECTIVE: To explore the injury of insulin resistance on cardiac muscle cell and matrix, and the relationship between insulin resistance and diabetic cardiomyopathy. METHODS: Twenty four Wistar rats of 6 months were randomly divided into normal control (N), insulin resistance group (I), diabetic group (D). Euglycemic insulin clamp technique (EICT) was used to determine insulin resistance (IR). Cadiocyte apoptosis was evaluated by TUNEL. Heart weight (HW) and body weight (BW) were measured to calculate HW/BW. Ultra-microstructure of cardiac muscle cell and structure of heart was observed. Masson dyeing, hydroxyproline detection and immunohistochemistry were used to measure the levels of collagen protein. RESULTS: Compared with controls, GIR decreased remarkably in D group and I group (P < 0.01). The number of apoptosis cell in I group was lower than that of D group (P < 0.01), and higher than that of N group (P < 0.01). Injury change of ultramicrostructure of myocardial cell was observed in the rats with type 2 diabetes mellitus or insulin resistance. Interstitial fibrosis of heart occurred in D group and I group. Content of Hydroxyproline, the level of I , III type of collagen, and the total level of collagen in I group were lower than those in D group, and higher than those in N group (P < 0.05). CONCLUSION: Insulin resistance in the rats with type 2 diabetes mellitus or insulin resistance can injury myocardial cell and matrix.

[Infrared spectrum and nuclear magnetic resonance analysis of the alkaloid extract of Gelsemium produced in east Guangdong province].

OBJECTIVE: To identify the structure of the alkaloid extract of Gelsemium from east Guangdong province of China. METHODS: Fourier transform infrared (FTIR) absorption spectrometry, hydrogen and carbon spectra of nuclear magnetic resonance (NMR) and distortionless enhancement by polarization transfer (DEPT) analysis were used for the structural identification of the alkaloid exstract of Gelsemium. RESULTS: The frequency, intensity and shape of the extract's characteristic peaks in infrared absorption spectra (4,000.0-400.0 cm(-1)) and (1)H NMR, (13)C NMR were recognized and compared. The molecular structure of the sample was consistent with the theoretically derived model. CONCLUSION: The extract is structurally identical to koumine, which may provide evidence for its safe clinical application and establishment of Chinese medicine fingerprint database of Gelsemium.

[Therapeutic effects of koumine on psoriasis: an experimental study in mice].

OBJECTIVE: To study the therapeutic effects of koumine on psoriasis in mouse models. METHODS: The effects of koumine on epithelial cell mitosis and epidermal cell differentiation was evaluated by collecting the samples of the vaginal mucous and squamous epidermis at the tail of mice treated with methotrexate or koumine at different doses. The levels of interleukin (IL)-2 were detected with enzyme-linked immunosorbent assay. RESULTS: High and intermediate doses of koumine showed remarkable inhibitory effect on mouse vaginal epithelial cell mitosis and promoted the formation of epidermal granular layer in the scales at the mouse tail. Three concentrations at 6, 30, 150 mg/kg of koumine decreased serum IL-2 level in the mice. CONCLUSION: The therapeutic effect of koumine against psoriasis is related to the inhibition of epidermal cell proliferation, promoting the formation of granular cells and decreasing the serum level of IL-2.

[Effect of koumine on proliferation of murine CD4+ T cells purified by magnetic-activated cell sorting in vitro].

OBJECTIVE: To assess the separation efficiency of magnetic-activated cell sorting in the purification of CD4+ T cells from murine spleen, and observe the effects of koumine on the proliferation of the separated cells. METHODS: CD4+ T cells were isolated from murine spleen by magnetic-activated cell sorting (MiniMACS). Fluorescence-activated cell sortering was employed to determine the purity of CD4+ T cells before and after the separation procedure followed by evaluation of the cell viability using trypan blue staining. Concanavalin A- (ConA, 5 microg/ml) or phytahematoagglutinin (PHA,1 mg/ml)-induced murine T cells were treated with different concentrations of koumine (10-320 microg/ml), and their proliferation was determined by MTT colorimetry, and enzyme-linked immunosorbent assay was used to measure IL-2 level in the cell culture supernatant. RESULTS: The purity of CD4+ T cells reached (90.3+/-5.8)% after the purification with a cell viability of (94.9+/-3.6)%. Koumine (20-320 microg/ml) dose-dependently inhibited ConA- or PHA-induced proliferation of murine lymphocytes as compared with the controls (P<0.05). Koumine (20, 100, and 200 microg/ml) significantly decreased the level of IL-2 in comparison with the control group (P<0.05). CONCLUSIONS: CD4+ T cells of high purity can be obtained from murine spleen using MiniMACS without impairing the viability of the cells. Koumine significantly inhibits the proliferation of murine CD4+ T cells due to its immunosuppressive effect and inhibition of IL-2 secretion.

[Current status of study on selective cyclooxygenase-2 inhibitors and evaluation of its application].

Selective cyclooxygenase-2 inhibitors have anti-inflammatory efficacy and can reduce the side effects and toxicity induced by inhibition of cyclooxygenase-1, thus can be widely used in clinical practice. However, the adverse effects of these drugs should be given their due attention. Currently, looking for better selective cyclooxygenase-2 inhibitors has become a hot topic in developing the non-steroidal anti-inflammatory drugs.

[Extraction and separation of koumine from Gelsemium alkaloids].

OBJECTIVE: To establish a method for isolating and identifying koumine. METHODS: Koumine was first extracted from Gelsemium alkaloids by using chloroform, which was further separated and purified by column chromatograph, and identified by thin-layer chromatography. RESULTS AND CONCLUSION: Koumine crystals were isolated and purified from Gelsemium alkaloids effectively.

[Comparative study of uniform design and orthogonal design in the extraction of Gelsemium alkaloids].

OBJECTIVE: To develop a simple and efficient method for extracting Gelsemium alkaloids. METHODS: Uniform design and orthogonal design were respectively utilized to optimize the 3 factors in the extraction process, namely the type of solvent used, the solid-to-liquid ratio in the extraction system and the reflux time. RESULTS: Both of the design methods adopted trichloromethane as the solvent, with the solid-to-liquid ratio of 1:7.5 and reflux time of 3 h with 3 repetitions for the highest yield of alkaloids. CONCLUSION: Similar results are obtained from the two design methods for extracting Gelsemium alkaloids.