Lymphocytes proliferate in blood and lymph nodes following interleukin-2 therapy in addition to highly active antiretroviral therapy.

BACKGROUND: Substantial redistribution of lymphocytes occurs upon the initiation of highly active antiretroviral therapy (HAART) and immune-based HIV therapies. OBJECTIVE: To evaluate the relative contribution of apoptosis and proliferation to changes in lymphocyte populations in peripheral blood and lymph node resulting from interleukin-2 (IL-2) therapy in patients receiving stable HAART. METHODS: Lymphocyte apoptosis was analyzed on various subtypes using fluorescence activated cell sorting with an annexin-V antibody in peripheral blood and by the TUNEL (terminal uridine nucleotide end labelling) method in corresponding lymph node sections. Lymphocyte proliferation was evaluated using an antibody against the cell cycle-associated marker Ki-67 (MIB-1) in peripheral blood and lymph nodes. RESULTS: A transient increase in apoptosis was seen in peripheral blood and lymph nodes during a cycle of subcutaneous IL-2. A pronounced proliferative effect of IL-2 (from 6.4% of total lymphocytes in patients only treated with HAART to 23.4% in those treated with HAART + IL-2) was detected in peripheral blood, affecting the CD4, CD8 and CD16/56 subsets to a similar extent. Remarkably, the proliferative effect also occurred in lymphoid tissues. While the lymph node structure gradually disintegrated over 24 months in some individuals, the amount of proliferating lymphocytes, including CD4 cells, B cells and follicular dendritic cells, greatly increased upon IL-2, while HIV RNA load in lymph nodes remained unaffected. CONCLUSION: These results show that IL-2 leads to lymphocyte proliferation in peripheral blood and lymph nodes without an impact on viral load in lymphoid tissue. These results have important implications for attempts to reconstitute the immune system in HIV disease.     

Role of inducible nitric oxide synthase in myocardial ischemia-reperfusion injury in sleep-deprived rats

Introduction

REM sleep deprivation (SD) decreases tolerance of the rat heart to ischemia-reperfusion (IR) injury; the underlying mechanisms, however, are unknown. This study aimed at determining whether changes in iNOS, Bax, and Bcl-2 gene expression are involved in this detrimental effect.

Method

SD was induced by flowerpot technique for a period of 4 days. This method is simple and able to induce sleep fragmentation which occurs as one of the sleep disorder symptoms in clinical conditions. The hearts of control and SD rats were perfused in Langendorff apparatus and subjected to 30 min ischemia, followed by 90 min reperfusion. The hemodynamic parameters (left ventricular developed pressure (LVDP), and ± dp/dt), NOx (nitrite + nitrate) level, infarct size, and mRNA expression of iNOS, Bax, and Bcl-2 were measured after IR.

Results

SD rats had lower recovery of post-ischemic LVDP (32.8 ± 2.5 vs. 51.5 ± 2.1 mmHg; P < 0.05), + dp/dt (1555 ± 66 vs. 1119.5 ± 87 mmHg/s; P < 0.05) and ? dp/dt (1437 ± 65 vs. 888 ± 162 mmHg/s; P < 0.05). SD rats also had higher NOx levels (41.4 ± 3.1 vs. 22.4 ± 3.6 μmol/L; P < 0.05) and infarct size (64.3 ± 2.3 vs. 38.3 ± 1.6%; P < 0.05) after IR, which along with LVDP, ± dp/dt restored to near normal status in the presence of aminoguanidine, a selective iNOS inhibitor. Following IR, expression of iNOS and Bax increased and Bcl-2 decreased (502, 372, and 54%, respectively) in SD rats; whereas in the presence of aminoguanidine, expression of iNOS and Bax significantly decreased and Bcl-2 increased (165, 168, and 19%, respectively).

Conclusion

Higher expression of iNOS and subsequent increase in apoptosis in the hearts after IR may contribute to less tolerance to myocardial IR injury in SD rats.

     

Appropriateness of angiography for suspected coronary artery disease

The aim of this study was to assess the appropriate use of diagnostic catheterizations (DC) for the patients with suspected coronary artery disease performed in Iran. The Electronic Health Record System database and manual review of files were utilised to collect data between 2012 and 2014. Patients were categorized in three groups as appropriate, uncertain, and inappropriate usage of DC and the logistic regression was used to investigate the relationships between variables. One-quarter of the 2458 angiographies were rated as inappropriate, out of which 99% had no previous stress test. The rate of inappropriate DC between various hospitals were approximately the same. The regression showed that some risk factors (Sex, high cholesterol, smoking, chronic heart failure, renal failure, diabetes) were significantly associated with inappropriate rate.     

Brief Report: A model for a partnership of lipid transfer proteins and scramblases in membrane expansion and organelle biogenesis

The autophagy protein ATG2, proposed to transfer bulk lipid from the endoplasmic reticulum (ER) during autophagosome biogenesis, interacts with ER residents TMEM41B and VMP1 and with ATG9, in Golgi-derived vesicles that initiate autophagosome formation. In vitro assays reveal TMEM41B, VMP1, and ATG9 as scramblases. We propose a model wherein membrane expansion results from the partnership of a lipid transfer protein, moving lipids between the cytosolic leaflets of apposed organelles, and scramblases that reequilibrate the leaflets of donor and acceptor organelle membranes as lipids are depleted or augmented. TMEM41B and VMP1 are implicated broadly in lipid homeostasis and membrane dynamics processes in which their scrambling activities likely are key.     

Mitotic Index is an Independent Predictor of Recurrence‐Free Survival in Meningioma

While World Health Organization (WHO) grading of meningioma stratifies patients according to recurrence risk overall, there is substantial within‐grade heterogeneity with respect to recurrence‐free survival (RFS). Most meningiomas are graded according to mitotic counts per unit area on hematoxylin and eosin sections, a method potentially confounded by tumor cellularity, as well as potential limitations of accurate mitotic figure detection on routine histology. To refine mitotic figure assessment, we evaluated 363 meningiomas with phospho‐histone H3 (Ser10) and determined the mitotic index (number of mitoses per 1000 tumor cells). The median mitotic indices among WHO grade I (n = 268), grade II (n = 84) and grade III (n = 11) tumors were 1, 4 and 12. Classification and regression tree analysis to categorize cut‐offs identified three subgroups defined by mitotic indices of 0–2, 3–4 and ≥5, which on univariate analysis were associated with RFS (P < 0.01). In multivariate analysis, mitotic index subgrouped in this manner was significantly associated with RFS (P < 0.01) after adjustment for Simpson grade, WHO grade and MIB‐1 index. Mitotic index was then examined within individual WHO grade, showing that for grade I and grade II meningiomas, mitotic index can add additional information to RFS risk. The results suggest that the use of a robust mitotic marker in meningioma could refine risk stratification.     

Liver transplantation as a definitive treatment for familial hypercholesterolemia: A series of 36 cases

FH is a genetic disorder characterized by an increase in serum LDL and total cholesterol values. The afflicted patients are at increased risk of premature atherosclerosis and myocardial infarction. Different treatment modalities are present, including pharmacological agents and surgical procedures. The most effective method of therapy in refractive cases is liver transplantation. Herein, we report our experience on 36 cases of patients with FH undergoing liver transplantation in our center, the main referral center of liver transplantation in Iran. The clinical findings, hospital courses, post‐operative complications, and patient follow‐up are also described.