Bacterial translocation induces proinflammatory responses and is associated with early death in experimental severe injury

Objective

An experimental model of severe injury with great lethality was studied to define the impact of bacterial translocation on survival and on inflammatory response.

Methods

Forty-one rabbits were divided into two groups: A, femur myotomy; and B, myotomy and fracture of the femoral bone. Vital signs and survival were recorded. Serum circulating endotoxins (lipopolysaccharides; LPS) were determined and tissue cultures were performed at necropsy. A subgroup of animals was sacrificed at 48 h post injury; LPS was determined in abdominal aorta and portal vein, apoptosis of spleen cells was assessed by flow cytometry, and ex vivo production of tumor necrosis factor alpha by splenocytes was measured.

Results

Tissue bacterial burden was increased in animals that died early (i.e., within 48 h after injury) versus rabbits that died later. Portal vein LPS at 48 h was increased in group B compared with group A, whereas circulating LPS did not differ. No difference in apoptosis of either lymphocytes or macrophages of the spleen was found in group B compared with group A. Following stimulation with LPS or phytohemagglutinin, tumor necrosis factor α production by splenocytes of group B was greater than that of group A.

Conclusions

Bacterial translocation primes enhanced proinflammatory responses and it is associated with early death in severe trauma.     

PDE5 inhibition against acute renal ischemia reperfusion injury in rats: does vardenafil offer protection?

Purpose

To evaluate the effect of vardenafil on renal function after renal ischemia–reperfusion (IR) injury (IRI) in a rat model.

Materials and methods

Seventy-one Wistar rats were divided into 7 groups including (1) a vehicle-treated group, (2) a vehicle pretreated-IR group, (3–6) vardenafil pretreated-IR groups in doses of 0.02, 0.2, 2 and 20 μg/kg, respectively, (7) a group of IR followed by treatment with 2 μg/kg of vardenafil. Vardenafil or vehicle solution was administered one hour before unilateral nephrectomy and the induction of 45 min of ischemia on the contralateral kidney by clamping of renal pedicle. Four hours of reperfusion were allowed after renal ischemia. Studied parameters were serum creatinine, fractional excretion of sodium (FENa), and histological evaluation of renal specimens. In addition, renal tissue cGMP levels, ERK1/2 phosphorylation as well as renal function by renal scintigraphy were also evaluated.

Results

Administration of vardenafil before the induction of ischemia resulted in a significant reduction in creatinine and FENa levels as well as in less histological lesions observed in treated kidneys in comparison with the vehicle-treated group. The underlying mechanism of cytoprotection was cGMP depended and involved the phosphorylation of ERK proteins. Renal scintigraphy confirmed that PDE5 inhibition attenuates renal IRI.

Conclusions

Vardenafil attenuates renal IRI. Based on similar results from relevant studies on other PDE-5 inhibitors in renal and cardiac IRI, it can be assumed that all PDE-5 inhibitors share a common mechanism of cytoprotection.     

Hemangiopericytoma/solitary fibrous tumor of pectoralis major muscle mimicking a breast mass

INTRODUCTIONHemangiopericytoma (HPC)/solitary fibrous tumor (SFT) is a very uncommon tumor of uncertain malignant behavior. In 1942, Stout and Murray first characterized these neoplasms as “vascular tumors arising from Zimmerman's pericytes” and till now hemangiopericytomas and solitary fibrous tumors of the soft tissues are regarded as features of the same entity in the soft tissue fascicle.PRESENTATION OF CASEWe present a case of hemangiopericytoma/solitary fibrous tumor of the pectoralis major muscle in a 33-year-old female. She first noticed a painless mass in her right breast. Ultrasound of the breast revealed a large heterogeneously hypoechoic lesion within the pectoralis major muscle. Fine needle aspiration of the tumor did not produce any meaningful result. The lesion was completely removed by surgical resection. Histologically, the tumor had staghorn-like vasculature and immunohistochemistry for CD34 was positive, whereas desmin, smooth-muscle actin, S-100 protein, cytokeratins (AE1/AE3) and epithelial membrane antigen (EMA) were all negative. A diagnosis of hemangiopericytoma/solitary fibrous tumor was rendered.DISCUSSIONTumors comprising the HPC/SFT spectrum represent a small subset of soft tissue sarcomas and are found virtually at any site in the body. Wide surgical resection can achieve favorable long-term survival.CONCLUSIONDue to the rarity and unpredictable biological potential of these tumors, long-term follow-up is mandatory even after radical resection, because recurrence or development of metastasis may be delayed many years.     

DNA–histone complexes as ligands amplify cell penetration and nuclear targeting of anti‐DNA antibodies via energy‐independent mechanisms

We have generated three monoclonal cell‐penetrating antibodies (CPAbs) from a non‐immunized lupus‐prone (NZB × NZW)F₁ mouse that exhibited high anti‐DNA serum titres. These CPAbs are polyreactive because they bind to DNA and other cellular components, and localize mainly in the nucleus of HeLa cells, albeit with a distinct nuclear labelling profile. Herein, we have examined whether DNA–histone complexes (DHC) binding to CPAbs, before cell entry, could modify the cell penetration of CPAbs or their nuclear staining properties. By applying confocal microscopy and image analysis, we found that extracellular binding of purified CPAbs to DHC significantly enhanced their subsequent cell‐entry, both in terms of percentages of positively labelled cells and fluorescence intensity (internalized CPAb amount), whereas there was a variable effect on their nuclear staining profile. Internalization of CPAbs, either alone or bound to DHC, remained unaltered after the addition of endocytosis‐specific inhibitors at 37° or assay performance at 4°, suggesting the involvement of energy‐independent mechanisms in the internalization process. These findings assign to CPAbs a more complex pathogenetic role in systemic lupus erythematosus where both CPAbs and nuclear components are abundant.     

Efficacy and safety of a low monthly dose of intravenous iron sucrose in peritoneal dialysis patients

Purpose

Scientific data regarding intravenous iron supplementation in peritoneal dialysis (PD) patients are scarce. In attempting to administer the minimum monthly IV iron dose that could improve erythropoiesis, we wanted to assess the safety and efficacy of monthly maintenance intravenous administration of 100 mg iron sucrose in PD patients.

Methods

In a 9-month prospective study, all clinically stable PD patients received intravenously 200 mg of iron sucrose as a loading dose, followed by monthly doses of 100 mg for five consecutive months. Levels of hemoglobin (Hb), ferritin, transferrin saturation (TSAT), reticulocyte hemoglobin content (CHr) and C-reactive protein (CRP) were measured before each administration and 3 months after the last iron infusion. Also, doses of concurrent erythropoietin administration were recorded.

Results

Eighteen patients were eligible for the study. Mean levels of Hb and ferritin increased significantly (from 10.0 to 10.9 mg/dL, p?=?0.01 and from 143 to 260 ng/mL, p?=?0.005), as well as the increase in TSAT levels approached borderline significance (from 26.2 to 33.1%, p?=?0.07). During the 6 months of iron administration, the erythropoietin dose was reduced in five patients and discontinued in one. During the 3 months following the last iron infusion, three of them again raised the erythropoietin dose to previous levels. None of the patients experienced any side effects related to IV iron administration.

Conclusions

A monthly maintenance intravenous dose of 100 mg iron sucrose may be a practical, effective, and safe in the short term, treatment of anemia in PD patients resulting in improved hemoglobin levels, iron indices, and erythropoietin response.

     

Imbalance of tissue inhibitors of metalloproteinases (TIMP) – 1 and – 4 serum levels,in patients with inflammatory bowel disease

Background  

Tissue inhibitors of metalloproteinases (TIMPs) play a key role in tissue degradation and remodeling. Since chronic inflammation is associated with tissue remodeling in inflammatory bowel disease (IBD), we evaluated serum TIMP-1 and TIMP-4 levels in IBD patients, in comparison with healthy controls (HC).     

Treatment with bortezomib‐based regimens improves overall response and predicts for survival in patients with primary or secondary plasma cell leukemia: Analysis of the Greek myeloma study group

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, with poor outcome. Bortezomib‐based regimens (BBR) are highly effective in myeloma, but there is limited information about their efficacy and safety in PCL. Thus, we retrospectively collected data from 42 consecutive PCL patients (25 with primary PCL‐pPCL and 17 with secondary PCL‐sPCL) to explore the role of BBR in this entity. BBR were administered in 29 of 42 patients, while 6 of 25 patients with pPCL underwent autologous transplantation. Objective response (≥partial response) was significantly higher in patients treated with BBR versus conventional therapies (69% vs. 30.8%, P = 0.04); 27.5% of patients treated with BBR achieved at least very good partial response (vgPR). The highest ORR was observed in pPCL patients treated with BBR (88.9%; ≥vgPR: 33.3%). In BBR‐group, grade 3 of 4 hematological, neurological and renal toxicity and neutropenic infections were observed in 41.4%, 7%, 3.4%, and 31%, respectively. With a median follow‐up of 51 months, median overall survival (OS) for patients treated with BBR versus conventional therapies was 13 versus 2 months (P < 0.007). Median OS of patients with pPCL and sPCL treated with BBR was 18 and 7 months, respectively (P < 0.001). In the multivariate analysis normal PLTs, treatment with BBR and high quality response were the only powerful predictors for survival. Our study carrying the longest reported median follow‐up, demonstrated that treatment of PCL with BBR induces high response rates and prolongs survival over conventional therapies, regardless of additional autologous transplantation rescue or established high risk features, with manageable toxicity. Am. J. Hematol. 89:145–150, 2014. © 2013 Wiley Periodicals, Inc.