No abstract

Background: Whether electroacupuncture (EA) stimulation at different frequencies has a similar effect on spared nerve injury (SNI) as other neuropathic pain models, and how EA at different frequencies causes distinct analgesic effects on neuropathic pain is still not clear. Methods: Adult male Sprague-Dawley rats were randomly divided into sham SNI, SNI, 2 Hz, 100 Hz and sham EA groups. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were measured. EA was performed once a day on days 1 to 14 after SNI. The expressions of transient receptor potential cation subfamily V member 1 (TRPV1) and peripheral purinergic P2X receptor 3 (P2X3) were determined by western blotting and immunofluorescence. TRPV1 siRNA and P2X3 siRNA were administered by intrathecal injection. TRPV1 or P2X3 agonists were combined with EA. Results: There were significant decreases in PWT, but no changes in PWL in the 14 days after SNI. EA using 2- or 100-Hz stimulation similarly increased PWT at every time point. The cytosol protein expression of P2X3 in the L4–L6 dorsal root ganglia (DRG) increased, but the expression of TRPV1 decreased in the SNI model. Both these effects were ameliorated by EA, with 2-Hz stimulation having a stronger effect than 100-Hz stimulation. Blocking either TRPV1 or P2X3 specific siRNAs attenuated the decreased PWT induced by SNI. Administration of either a TRPV1 or P2X3 agonist inhibited EA analgesia. Conclusion: 2- and 100-Hz EA similarly induced analgesic effects in SNI. This effect was related to up-regulation and down-regulation, respectively, of cytosol protein expression of P2X3 and TRPV1 in L4–L6 DRG, with 2 Hz having a better effect than 100 Hz.

Background Tuberculosis (Tb) is the most frequent opportunistic infection among people living with HIV infection. The impact of Tb co-infection in the establishment and maintenance of the HIV reservoir is unclear. Method We enrolled 13 HIV-infected patients with microbiologically confirmed Tb and 10 matched mono-HIV infected controls. Total HIV DNA in peripheral blood mononuclear cells (PBMCs), plasma interleukin-7 (IL-7) concentrations and the activities of indoleamine 2,3-dioxygenase (IDO) were measured for all the participants prior to therapy and after antiretroviral therapy (ART). Results After a duration of 16 (12, 22) months’ ART, patients co-infected with Tb who were cured of Tb maintained higher levels of HIV DNA compared with mono-HIV infected patients [2.89 (2.65- 3.05) log10 copies/106 cells vs. 2.30 (2.11–2.84) log10 copies/106 cells, P = 0.008]. The levels of on-ART HIV DNA were positively correlated with the baseline viral load (r = 0.64, P = 0.02) in Tb co-infected group. However, neither plasma IL-7 concentration nor plasma IDO activity was correlated with the level of on-ART HIV DNA. Conclusions Tb co-infection was associated with the increased surrogate marker of the HIV reservoir, while its mechanism warrants further examination.

The incidence rate of tuberculosis (TB) in patients with human immunodeficiency virus (HIV) infection is 26 times higher than that in other patients. Patients with both infections require long-term combination therapy, which increases therapy complexity and might lead to serious adverse reactions and drug-drug interactions. To optimize therapy for patients with HIV and TB coinfection, we developed an ultra-high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method to simultaneously quantify four antituberculosis drugs and one isoniazid (INH) metabolite. Blood samples (n ¼ 32) from 16 patients with HIV and TB coinfection were collected. Plasma protein precipitation with acetonitrile was followed by a hydrazine reaction between INH and cinnamaldehyde (CA) to produce phenylhydrazone (CA-INH) and dilution with heptafluorobutyric acid. The separation was performed on an Acquity UHPLC HSS T3 1.8 μm column (2.1 Â 100 mm, Waters) with a mobile phase consisting of 10 mmol/L ammonium formate (pH ¼ 4) in water (solvent A) and 0.1 % formic acid in methanol (solvent B) in a gradient elution. The compounds were detected using a positive multiple reaction monitoring model. INH, acetyl-INH (AC-INH), rifampicin (RIF), ethambutol (EMB), and pyrazinamide (PZA) showed good linear relationships in their quantitative ranges, with lower limits of quantification of 48, 192, 200, 96, and 480 ng/mL, respectively. The inter-and intraday precision was within 15 %, and the accuracy was between 85 % and 115 %. The mean plasma concentrations of INH, AC-INH, RIF, EMB, and PZA in patients were 1990.23 (24-16 600), 863.06 (96-2880), 3507.05 (229-9800), 808.10 (149-2130), and 18 838.33 (240-34 800) ng/mL, respectively. The plasma concentrations detected in the 16 patients were lower than the targeted concentrations in HIV-negative TB patients. In summary, we developed a simple UHPLC-MS/MS method for simultaneous quantification of first-line TB drugs, and successfully applied it for therapeutic drug monitoring in patients with HIV and TB coinfection. This method will facilitate monitoring of TB drugs in the future.

Objectives People living with HIV (PLWH) have a high risk of kidney injury. Measurement of serum creatinine, along with proteinuria, is not sensitive to detect early kidney injury. Here, we investigated novel urinary biomarkers of early renal injury in PLWH. Methods We performed a cross‐sectional study of 166 antiretroviral‐naïve PLWH and 99 HIV‐negative persons who all had an estimated glomerular filtration rate > 90 mL/min/1.73 m2. We compared the levels of seven urinary biomarkers between the two groups using the propensity score matching (PSM) approach and explored the risk factors associated with elevated urinary biomarkers in PLWH. Results Eighty‐three pairs were successfully matched based on PSM. Compared with the HIV‐negative group, the HIV‐positive group had higher ratios of N‐acetyl‐β‐D‐glucosaminidase (NAG) to urine creatinine (UCr), alpha1‐microglobulin (α1‐M) to UCr, kidney injury marker‐1 (KIM‐1) to UCr, neutrophil gelatinase‐associated lipocalin to UCr, and epidermal growth factor to UCr, whereas the Tamm–Horsfall protein to UCr ratio and the abnormal albumin to UCr ratio were not significantly different. Positive correlations were observed between HIV RNA level and NAG: UCr (rs = 0.32; P < 0.001) and α1‐M:UCr (rs = 0.24; P = 0.002) ratios, and negative correlations were observed between CD4 cell count and NAG:UCr (rs = –0.34; P < 0.001), KIM‐1:UCr (rs = –0.16; P = 0.042) and α1‐M:UCr (rs = –0.36; P < 0.001) ratios. In multivariate linear regression analyses, older age, lower total cholesterol and higher HIV RNA were independently associated with higher NAG:UCr; older age, lower total cholesterol and lower CD4 cell count were independently associated with higher α1‐M:UCr. Conclusions In comparioson with HIV‐negative participants, PLWH were more likely to have tubular injury. Early antiretroviral treatment might mitigate the development of kidney injury.