Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects

Aims/hypothesis The ACE insertion/deletion polymorphism has been examined for association with diabetic nephropathy over the past decade with conflicting results. To clarify this situation, we conducted a comprehensive meta-analysis encompassing all relevant studies that were published between 1994 and 2004 and investigated this potential genetic association.Methods A total of 14,727 subjects from 47 studies was included in this meta-analysis. Cases (n=8,663) were type 1 or 2 diabetic subjects with incipient (microalbuminuria) or advanced diabetic nephropathy (proteinuria, chronic renal failure, end-stage renal disease). Control subjects (n=6,064) were predominantly normoalbuminuric.Results No obvious publication bias was detected. Using a minimal-case definition based on incipient diabetic nephropathy, subjects with the II genotype had a 22% lower risk of diabetic nephropathy than carriers of the D allele (pooled odds ratio [OR]=0.78, 95% CI=0.69–0.88). While there was a reduced risk of diabetic nephropathy associated with the II genotype among Caucasians with either type 1 or type 2 diabetes, the association was most marked among type 2 diabetic Asians (Chinese, Japanese, Koreans) (OR=0.65, 95% CI=0. 51–0.83). This OR is significantly different from the OR of 0.90 (95% CI= 0.78–1.04) that was obtained for type 2 diabetic Caucasians (p=0.019). Using a stricter case definition based on advanced diabetic nephropathy, a comparable risk reduction of 24–32% was observed among the three subgroups, although statistical significance was reached only among Asians.Conclusions/interpretation The results of our meta-analysis support a genetic association of the ACE Ins/Del polymorphism with diabetic nephropathy. These findings may have implications for the management of diabetic nephropathy using ACE inhibitors especially among type 2 diabetic Asians.     

Sweet potato leaf extract inhibits the simulated in vitro gastrointestinal digestion of native starch

Several studies have reported the therapeutic use of caffeoylquinic acid (CQA) derivatives in the management of hyperglycemia. This study used a simulated in vitro gastrointestinal digestion model to assess the inhibitory effects of CQA derivatives-rich sweet potato leaf extract (SPLE) and a commercially produced green coffee bean extract (GCBE), each with total polyphenols contents of 452 mg g⁻¹ and 278 mg g⁻¹, respectively, against starch digestion. The changes in the amounts of total polyphenols and total CQA derivatives during in vitro gastrointestinal digestion were also examined. The results indicated that both extracts contained substantial levels of CQA derivatives (136 mg g⁻¹ and 83.5 mg g⁻¹ of extract for SPLE and GCBE, respectively). The amounts of total polyphenols and total CQA derivatives in 20 mg of SPLE and GCBE samples decreased from 9.04 mg to 0.58 mg and from 5.56 mg to 0.58 mg, and from 2.72 mg to 0.16 mg and from 1.67 mg to 0.10 mg, respectively, following in vitro gastrointestinal digestion and subsequent dialysis. When SPLE and GCBE were accompanied with starch for in vitro digestion test, they both exhibited inhibitory effect against starch digestion during simulated intestinal digestion, with estimated half maximal inhibitory concentration (IC₅₀) values of 4.91 mg and 6.06 mg polyphenols, respectively. The amount of glucose permeated through dialysis membrane also decreased significantly in comparison with the extract-negative control. Thus, both SPLE and GCBE were capable of modulating the release of glucose from starch digestion in simulated intestinal tract. The observed inhibitory effects against glucose release were presumably due in part to the presence of CQA derivatives in the tested extracts. The SPLE had higher inhibitory effect against in vitro starch digestion than the commercially prepared reference GCBE. Therefore, the SPLE might be used to manage hyperglycemia over the long term.     

Effectiveness and safety profiling of zolpidem and acupressure in CKD associated pruritus: An interventional study

Background:Chronic kidney disease (CKD)-associated pruritus (CKD-aP) contributes to poor quality of life, including reduced sleep quality and poor sleep quality is a source of patient stress and is linked to lower health-related quality of life. This study aimed to investigate the effectiveness of zolpidem 10 mg and acupressure therapy on foot acupoints to improve the sleep quality and overall quality of life among hemodialysis patients suffering from CKD-aP.Method:A multicenter, prospective, randomized, parallel-design, open label interventional study to estimate the effectiveness of zolpidem (10 mg) oral tablets versus acupressure on sleep quality and quality of life in patients with CKD-aP on hemodialysis. A total of 58 hemodialysis patients having sleep disturbance due to CKD-aP completed the entire 8-week follow-up. The patients were divided into a control (acupressure) group of 28 patients and an intervention (zolpidem) group of 30 patients.Results:A total of 58 patients having CKD-aP and sleep disturbance were recruited. In the control group there was a reduction in the PSQI score with a mean ± SD from 12.28 ± 3.59 to 9.25 ± 3.99, while in the intervention group the reduction in PSQI score with a mean ± SD was from 14.73 ± 4.14 to 10.03 ± 4.04 from baseline to endpoint. However, the EQ5D index score and EQ-visual analogue scale (VAS) at baseline for the control group with a mean ± SD was 0.49 ± 0.30 and 50.17 ± 8.65, respectively, while for the intervention group the values were 0.62 ± 0.26 and 47.17 ± 5.82, respectively. The mean EQ5D index score in the control group improved from 0.49 ± 0.30 to 0.53 ± 0.30, but in the intervention group there was no statistical improvement in mean EQ5D index score from 0.62 ± 0.26 to 0.62 ± 0.27 from baseline to week 8. The EQ 5D improved in both groups and the EQ-VAS score was 2.67 points higher at week 8 as compared to baseline in the control group, while in the intervention group the score was 3.33 points higher at week 8 as compared to baseline. Comparing with baseline, the PSQI scores were significantly reduced after week 4 and week 8 (P =  < .001). Furthermore, at the end of the study, the PSQI scores were significantly higher in the control as compared to the intervention group (P = .012).Conclusion:An improvement in sleep quality and quality of life among CKD-aP patients on hemodialysis has been observed in both the control and intervention groups. Zolpidem and acupressure safety profiling showed no severe adverse effect other that drowsiness, nausea and daytime sleeping already reported in literature of zolpidem.     

COVID-19 associated coagulopathy in critically ill patients: A hypercoagulable state demonstrated by parameters of haemostasis and clot waveform analysis

Journal of Thrombosis and Thrombolysis - Patients with COVID-19 are known to be at risk of developing both venous, arterial and microvascular thrombosis, due to an excessive immuno-thrombogenic...     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

Ultra‐deep T cell receptor sequencing reveals the complexity and intratumour heterogeneity of T cell clones in renal cell carcinomas

The recognition of cancer cells by T cells can impact upon prognosis and be exploited for immunotherapeutic approaches. This recognition depends on the specific interaction between antigens displayed on the surface of cancer cells and the T cell receptor (TCR), which is generated by somatic rearrangements of TCR α‐ and β‐chains (TCRb). Our aim was to assess whether ultra‐deep sequencing of the rearranged TCRb in DNA extracted from unfractionated clear cell renal cell carcinoma (ccRCC) samples can provide insights into the clonality and heterogeneity of intratumoural T cells in ccRCCs, a tumour type that can display extensive genetic intratumour heterogeneity (ITH). For this purpose, DNA was extracted from two to four tumour regions from each of four primary ccRCCs and was analysed by ultra‐deep TCR sequencing. In parallel, tumour infiltration by CD4, CD8 and Foxp3 regulatory T cells was evaluated by immunohistochemistry and correlated with TCR‐sequencing data. A polyclonal T cell repertoire with 367–16 289 (median 2394) unique TCRb sequences was identified per tumour region. The frequencies of the 100 most abundant T cell clones/tumour were poorly correlated between most regions (Pearson correlation coefficient, –0.218 to 0.465). 3–93% of these T cell clones were not detectable across all regions. Thus, the clonal composition of T cell populations can be heterogeneous across different regions of the same ccRCC. T cell ITH was higher in tumours pretreated with an mTOR inhibitor, which could suggest that therapy can influence adaptive tumour immunity. These data show that ultra‐deep TCR‐sequencing technology can be applied directly to DNA extracted from unfractionated tumour samples, allowing novel insights into the clonality of T cell populations in cancers. These were polyclonal and displayed ITH in ccRCC. TCRb sequencing may shed light on mechanisms of cancer immunity and the efficacy of immunotherapy approaches. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.