Thrombopoietin and interleukin 11 have different modulatory effects on cell cycle and programmed cell death in primary acute myeloid leukemia cells.

The c-mpl ligand, thrombopoietin (TPO), is a physiologic regulator of platelet and megakaryocytic production, acting synergistically on thrombopoiesis with the growth factors interleukin 11 (IL-11), stem cell factor, interleukin 3 (IL-3), interleukin 6 (IL-6), and granulocyte-macrophage colony-stimulating factor. Because some of these growth factors, especially TPO and IL-11, are now being evaluated clinically to reduce chemotherapy-associated thrombocytopenia in cancer patients, we evaluated 25 acute myeloid leukemia (AML) samples to test whether TPO, IL-11, and other early-acting megakaryocyte growth factors can affect leukemic cell proliferation, cell cycle activation, and programmed cell death (PCD) protection. TPO induced proliferation in the majority of AML samples from an overall mean proportion of S-phase cells of 7.8% +/-1.5% to 14.5% +/- 2.1% (p = 0.0006). Concurrent G0 cell depletion was found in 47.3% of AML samples. TPO-supported leukemic cell precursor (CFU-L) proliferation was reported in 5 of 17 (29.4%) of the samples with a mean colony number of 21.4 +/- 9.6 x 10(5) cells plated. In 13 of 19 samples, a significant protection from PCD (from an overall mean value of 13% +/-0.7% to 8.8% +/- 1.8%;p = 0.05) was detected after TPO exposure. Conversely, IL-11-induced cell cycle changes (recruitment from G0 to S phase) were detected in only 2 of 14 samples (14.2%). In addition, IL-11 showed little, if any, effect on CFU-L growth (mean colony number = 17.5 9.5) or apoptosis. Combination of TPO with IL-11 resulted in only a slight increase in the number of CFU-L, whereas IL-3 and stem cell factor significantly raised the mean colony numbers up to 119.2 +/- 68.3 and 52.9 +/- 22.1 x 10(5) cells plated, respectively. We conclude that TPO induces cell cycle activation in a significant proportion of cases and generally protects the majority of AML blast cells from PCD. On the other hand, IL-11 has little effect on the cell cycle or PCD. Combination of both TPO and IL-11 is rarely synergistic in stimulating AML clonogenic growth. These findings may be useful for designing clinical studies aimed at reducing chemotherapy-associated thrombocytopenia in AML patients.     

双氯芬酸钠经皮电穿孔及电离子导入的研究

目的：考察离子导入和电穿孔对双氯芬酸钠经皮渗透的影响。方法：采用双室扩散池和SD大鼠皮、进行双氯芬酸钠饱和水溶液经皮被动扩散、离子导入（0．5mA/cm^2)和电穿孔导入（130V,740ms或100ms,200个脉冲,方波,占空比1：1）的 研究。结果：电穿孔和离子导入均能显著促进双氯芬酸钠的经皮渗透,其增渗倍数分别为25．1和7．5。延长脉冲7时间将改善电穿孔的促渗效果,初步研究表明本实验条件的电穿孔及离子导入未引起皮肤的损伤。结论：电穿孔技术可用于促进小分子解离型药物的经皮渗透。     

Aquaporin-4 autoantibodies in neuromyelitis optica spectrum disorders: comparison between tissue-based and cell-based indirect immunofluorescence assays

Background  

Neuromyelitis optica spectrum disorders (NMOSD) are severe central nervous system inflammatory demyelinating disorders (CNS IDD) characterized by monophasic or relapsing, longitudinally extensive transverse myelitis (LETM) and/or optic neuritis (ON). A significant proportion of NMOSD patients are seropositive for aquaporin-4 (AQP4) autoantibodies. We compared the AQP4 autoantibody detection rates of tissue-based indirect immunofluorescence assay (IIFA) and cell-based IIFA.     

Protective immunity against challenge with Leishmania (Leishmania) chagasi in beagle dogs vaccinated with recombinant A2 protein

In this study, we investigated in dogs the immunogenicity and protective immunity against Leishmania (Leishmania) chagasi infection induced by vaccination with a formulation containing the recombinant A2 protein, an amastigote specific antigen, and saponin. Vaccinated animals produced significantly increased levels of total IgG and IgG2, but not IgG1 anti-A2 antibodies, and remained negative in conventional leishmaniasis serodiagnostic methods. Significantly increased IFN-gamma and low IL-10 levels were detected in vaccinated animals before and after challenge, as compared to control animals. Importantly, while the symptoms onset appeared as early as three months after infection in most control dogs, 14 months after challenge, 5 out of 7 vaccinated dogs remained asymptomatic. Therefore, immunization with rA2 antigen was immunogenic and induced partial protection in dogs, and allowed the serological differentiation between vaccinated and infected animals, an important requirement for a canine visceral leishmaniasis (CVL) vaccine.     

[In Press] Posner-Schlossman syndrome induced LASIK keratectasia – a case report

Letter to the editor     

Low endogenous testosterone levels are associated with the extend of lymphnodal invasion at radical prostatectomy and extended pelvic lymph node dissection

Objective

To investigate clinical factors associated to lymphnodal metastasis load in patients who underwent to radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND).

Materials and methods

Between November 2014 and December 2019, ET was measured in 617 consecutive patients not under androgen deprivation therapy who underwent RP and ePLND. Lymphnode invasion (LNI) was codified as not present (N?=?0) or with one (N?=?1) or more than one metastatic node (N?>?1). The risk of multiple pelvic lymph node metastasis (N?>?1, mPLNM) was assessed by comparing it to the other two groups (N?>?1 vs. N?=?0 and N?>?1 vs. N?=?1). Then, we assessed the association between ET and lymphnode invasion for standard predictors, such as PSA, percentage of biopsy positive cores (BPC), tumor stage greater than 1 (cT?>?1) and tumor grade group greater than two (ISUP?>?2).

Results

Overall, LNI was detected in 70 patients (11.3%) of whom 39 (6.3%) with N?=?1 and 31 (5%) with N?>?1. On multivariate analysis, ET was inversely associated with the risk of N?>?1 when compared to both N?=?0 (odds ratio, OR 0.997; CI 0.994–1; p?=?0.027) as well as with N?=?1 cases (OR 0.994; 95% CI 0.989–1.000; p?=?0.015).

Conclusions

In clinical PCa, the risk of mPLNM was increased by low ET levels. As ET decreased, patients had an increased likelihood of mPLNM. Because of the inverse association between ET and mPLNM, higher ET levels were protective against aggressive disease. The influence of locally advanced PCa with high metastatic load on ET levels needs to be explored by controlled trials.

     

Shockwave Therapy in the Management of Complex Regional Pain Syndrome in Medial Femoral Condyle of the Knee

The aim of this prospective study was to assess the efficacy of shockwave (SW) therapy in the management of complex regional pain syndrome (CRPS). In this study, 30 patients (pts) who were affected by CRPS of the medial femoral condyle and unresponsive to previous standard physiotherapeutic and pharmacological treatment underwent 3 SW sessions at 72-h intervals, each consisting of 4000 shocks emitted by a MiniLith SL1 Storz electromagnetic generator. An energy flux density (EFD) of 0.035 or 0.09 mJ/mm² was used, depending on how well the patient endured the pain during the treatment. Satisfactory results were observed in 76.7% of the cases (23 pts) at the 2-month follow-up (FU) visit, and in 80% (24 pts) at the 6-month FU visit. The therapeutic effects of SW were caused by decreasing pain. The significant improvements we obtained bear witness to the potential value of SW therapy in the management of CRPS. (E-mail: angelanotarnicola@yahoo.it)     

Isolated molecular relapse in FIP1L1-PDGFRalpha hypereosinophilic syndrome after discontinuation and single weekly dose of imatinib: need of quantitative molecular procedures to modulate imatinib dose

Imatinib is the treatment of choice for FIP1L1-PDGFRα (F/P+) positive myeloproliferative neoplasms, but little is known about optimal dose and duration of treatment to maintain complete molecular remission once achieved. We describe a case of F/P+ patients who started imatinib and reached a molecular remission, but did relapse after 15 months of therapy for poor adherence to therapy, and re-obtained remission only with standard dose of 400 mg/day. We reviewed the literature and highlights the need of quantitative molecular procedures to modulate imatinib dose.