Paired kidney analysis of tacrolimus and cyclosporine microemulsion-based therapy in Chinese cadaveric renal transplant recipients

Few studies used paired kidneys for comparison between tacrolimus and cyclosporine in renal transplantation. Most of the published data used whole blood trough levels for drug monitoring. However, the use of limited sampling strategy and abbreviated formula to estimate the 12-h area under concentration-time curve (AUC(0-12)) allowed better prediction of drug exposure. Sixty-six first cadaveric renal transplant recipients receiving paired kidneys were randomized to receive either tacrolimus-based (n = 33) or cyclosporine microemulsion (Neoral)-based therapies (n = 33). Abbreviated AUC(0-12) was used for drug monitoring and dose titration. Mean follow-up duration was 2.8 +/- 2 years. The patient and graft survival were comparable. Fewer incidence of acute rejection was observed in tacrolimus group (15% vs. 27.3%) though the difference was not significant (P = 0.23). The absolute value and the rate of decline of creatinine clearance were both significantly better in tacrolimus-treated patients. Prevalence of hypertension, post-transplant diabetes mellitus, infection, and malignancy were similar in both groups. Prevalence of hypercholesterolemia (11/33 vs. 4/33) and gum hypertrophy (6/33 vs. 1/33) was more common in cyclosporine-treated patients (P = 0.04 in both parameters). This was the first prospective, randomized study with paired kidney analysis showing the renal function was significantly better in tacrolimus-treated patients than in cyclosporine-treated patients.     

Immunotactoid glomerulopathy with fingerprint immune deposits

Summary Immunotactoid glomerulopathy is a distinct clinico-pathological entity which has recently been defined. The term immunotactoid refers to highly organized immune depositions appearing as rod-like microtubular structures in ultrastructural examination. We describe a patient with mixed connective tissue disease who demonstrates characteristic features of immunotactoid glomerulopathy. The diagnosis was made after excluding amyloidosis, cryoglobulinaemia and lupus nephritis. In addition to immunotactoid microtubules, ultrastructural examination also demonstrated presence of fingerprint depositions which were intimately mixed with immunotactoid structures. Fingerprint deposits have been described in lupus nephritis and cryoglobulin-related nephropathy, but rarely in other glomerulonephritis. These unique findings in our patient may suggest a previously unsuspected relationship between the syndrome of immunotactoid glomerulopathy and systemic lupus erythematosus.     

Goji Berry Intake Increases Macular Pigment Optical Density in Healthy Adults: A Randomized Pilot Trial

Age-related macular degeneration (AMD) is the third leading cause of blindness worldwide. Macular pigment optical density (MPOD), a biomarker for AMD, is a non-invasive measure to assess risk. The macula xanthophyll pigments lutein (L) and zeaxanthin (Z) protect against blue light and provide oxidant defense, which can be indexed by MPOD. This study examined the effects of Z-rich goji berry intake on MPOD and skin carotenoids in healthy individuals. A randomized, unmasked, parallel-arm study was conducted with 27 participants, aged 45–65, who consumed either 28 g of goji berries or a supplement containing 6 mg L and 4 mg Z (LZ), five times weekly for 90 days. After 90 days, MPOD was significantly increased in the goji berry group at 0.25 and 1.75 retinal eccentricities (p = 0.029 and p = 0.044, respectively), while no changes were noted in the LZ group. Skin carotenoids were significantly increased in the goji berry group at day 45 (p = 0.025) and day 90 (p = 0.006), but not in the LZ group. Regular intake of goji berries in a healthy middle-aged population increases MPOD may help prevent or delay the development of AMD.     

Prenatal immune activation potentiates endocannabinoid-related plasticity of inhibitory synapses in the hippocampus of adolescent rat offspring

There is strong evidence that immune activation from prenatal infection increases the risk for offspring to develop schizophrenia. The endocannabinoid (eCB) system has been implicated in the pathophysiology of schizophrenia while models of cortical dysfunction postulate an imbalance between neuronal excitation and inhibition in the disorder. The current study examined the impact of prenatal immune activation on eCB-mediated inhibitory mechanisms. We compared two forms of eCB-related plasticity of evoked inhibitory postsynaptic currents, namely depolarization-induced suppression of inhibition (DSI) and metabotropic glutamate receptor-induced long term depression (mGluR-iLTD), in both the dorsal and ventral hippocampus between adolescent offspring from rat dams that received either saline or bacterial lipopolysaccharide (LPS) during pregnancy. Compared to prenatal saline offspring, prenatal LPS offspring displayed prolonged DSI and stronger mGluR-iLTD in the dorsal and ventral hippocampus, respectively. The sensitivity of mGluR-iLTD to the CB1 receptor antagonist AM251 was also lower in the dorsal hippocampus of prenatal LPS compared to prenatal saline offspring. Testing whether changes in eCB receptor signaling or levels could contribute to these changes in inhibitory transmission, we found region specific increases in 2-arachidonoylglycerol-stimulated signaling and in basal and mGluR-induced levels of anandamide in prenatal LPS offspring when compared to prenatal saline offspring. Our findings indicate that prenatal immune activation can lead to long-term changes in eCB-related plasticity of hippocampal inhibitory synaptic transmission in adolescent rat offspring. Perturbation of the eCB system resulting from prenatal immune activation could represent a mechanism linking early life immune events to the development of psychopathology in adolescence.     

Chemical comparison and classification of Radix Astragali by determination of isoflavonoids and astragalosides

Eleven major isoflavonoids and three major astragalosides in the xylem and bark of cultivated Radix Astragali (RA) from different cultivated regions of China were determined by high performance liquid chromatography. The results showed that the contents of astragalosides in the bark are up to 74-fold higher than in the xylem, and that thin roots contained more astragalosides than thick roots. Although the contents of isoflavonoids varied between samples, no significant difference was observed between the isoflavonoids content of xylem and bark, or between that of thin and thick roots. It was also found that the chemical profile of isoflavonoids in the xylem and bark are related to their cultivated regions. Constituents in either xylem or bark were divided into five groups according to their chemical structures: (1) Group 1 (G1), contained calycosin and related constituents; (2) Group 2 (G2), contained ononin and related constituents; (3) Group 3 (G3), contained (6aR,11aR)-3-hydroxy-9,10-dimethoxypterocarpan and related constituents; (4) Group 4 (G4), contained (3R)-7,2′-dihydroxy-3′,4′-dimethoxyisoflavan and related constituents; and (5) Group 5 (G5), contained astragalosides, compounds AG I, AG II, and AG IV. Based on the integrated contents of constituents in each group, the cultivated region of RA was successfully distinguished by principal components analysis (PCA). Chemical constituents in RA cultivated from different regions of China were compared and it was concluded that the quality of thin RA roots is better than thick RA roots.     

Burden and contributing factors associated with tricuspid regurgitation: a hospital-based study

Objectives: Tricuspid regurgitation (TR) is common in patients referred for cardiac assessment. Nonetheless, current estimates of its prevalence and contributing factors are limited. The aim of the present study was to evaluate the prevalence and demographics of TR in patients referred for echocardiography assessment at two University-affiliated hospitals.

Methods: A total of 6711 consecutive Chinese patients were recruited as part of the Chinese Valvular Heart Disease Study (CVATS).

Results: The most common valvular lesion was TR (54.7%), followed by mitral regurgitation (44.7%) and aortic regurgitation (26.5%). Clinically significant (moderate or severe) TR was identified in 8.4% with the proportion increased from 3.9% amongst those aged <51 to 15.9% in those aged ≥81. Multivariable adjustment demonstrated that significant TR was associated with age, congenital heart disease, chronic obstructive pulmonary disease, left-sided valvular heart disease (VHD), impaired left ventricular ejection fraction <50%, atrial fibrillation and pulmonary hypertension.

Conclusions: Among all types of VHD, TR was the most common and was identified in over half of the subjects and clinically significant in 8.4%. These unique data provide contemporary clinical and epidemiological characteristics of TR in a large cohort of patients referred for cardiac assessment and confirm the increased burden of TR in the aged population.     

Investigating the relationship between formal and informal care: An application using panel data for people living together

There is limited evidence on the relationship between formal and informal care using panel data in a U.K. setting and focused specifically on people living together (co‐residents). Using all 18 waves of the British Household Panel Survey (1991–2009), we analyse the effect of informal care given by co‐residents on the use of formal home care and health care services more generally. To account for endogeneity, we estimate models using random effects instrumental variable regression using the number of daughters as a source of exogenous variation. We find that a 10% increase in the monthly provision of informal care hours decreases the probability of using home help (formal home care) by 1.02 percentage points (p < .05), equivalent to a 15.62% relative reduction. This effect was larger for home help provided by the state (β = ?.117) compared with non‐state home help (β = ?.044). These results provide evidence that significant increases in the supply of informal care would reduce the demand for home‐help provision.     

CGRP对缺氧缺血新生鼠脑细胞内游离Ca2+的影响

目的探讨降钙素基因相关肽(CGRP)对缺氧缺血新生鼠脑细胞内游离Ca2+的影响及对脑损伤的保护作用.方法 7日龄SD大鼠制成HIE模型.⑴药物治疗组于模型后即给CGRP 3μg*kg-1*d-1,腹腔内注射,共3d;⑵生理盐水组每天给予同剂量生理盐水腹腔内注射;⑶正常对照组(假手术组).各组于3d后断头取脑,采用钙荧光指标剂Fura-2AM法测定脑细胞胞浆游离钙浓度[(Ca2+)].结果生理盐水组脑细胞内钙含量最高,(129.47±17.21nmol/L)与正常对照组(93.72±24.16nmol/L)比较有显著差异P＜0.01,而药物治疗组(103.35±12.46nmol/L)与正常对照组比较无显著差异.结论 CGRP能阻止新生鼠缺氧缺血脑损伤后细胞钙内流,降低细胞膜对Ca2+通透性可能是CGRP对脑缺氧缺血保护作用的重要机制.