Biocompatibility of Hemoglobin Solutions. II. The Inflammatory Reaction of Human Monocytes and Mouse Peritoneal Macrophages

This study explored the inflammatory mechanism of toxicity of hemoglobin solutions (Hb-S). Human monocytes and mouse activated peritoneal macrophages were incubated with seven different solutions. The first four consisted of non-cross-linked bovine Hb. Of these, Hb-SI was incompletely purified of stromal phospholipids, Hb-SII was contaminated with environmental bacterial endotoxins, Hb-SIII was pure hemoglobin, and Hb-SIV was pure Hb with the addition of superoxide dismutase (SOD), catalase (CAT), and mannitol (M). The other three solutions were made of pure bovine Hb cross-linked with different agents: Hb-SV, reacted with glutaraldehyde; Hb-SVI reacted with bis-3,5-dibromosalicyl fumarate (DBSF); and Hb-SVII reacted with a ring-opened dialdehyde derivative of 5'(pyro)-phosphate of adenosine (ATP) (o-ATP). The reaction of monocytes and macrophages was studied in terms of (a) O2-derived radicals, as determined by the measurement of H2O2 and lipid peroxides; (b) complement factor C3a desArg; (c) 6-keto-prostaglandin F1 alpha (stable metabolite of prostacyclin); and (d) TxB2 (stable metabolite of thromboxane) released into the culture supernatants. The most significant reactions were obtained with the solutions contaminated with stromal phospholipids or bacterial endotoxins. Pure Hb was less reactive. Further reduction in proinflammatory activity was achieved by the addition of oxygen radical-scavengers (SOD, CAT, and M), or by the cross-linking of Hb with DBSF or o-ATP.     

Biocompatibility of Hemoglobin Solutions. I. Reactions of Vascular Endothelial Cells to Pure and Impure Hemoglobins

Hemoglobin (Hb) solutions can cause vasoconstriction and activation of intravascular coagulation. Because the endothelium plays a major role in the regulation of vascular tone and hemostasis, a study was conducted of human umbilical vein endothelial cells (EC) incubated with various Hbs. Cell injury was evaluated by electron microscopy and the release of lactic dehydrogenase, H2O2, and procoagulant "tissue factor." Cell reaction was assessed by the measurement of 6-keto-prostaglandin F (PGF)1 alpha (metabolite of prostacyclin) and thromboxane B2 (metabolite of thromboxane A2). Incubation with unmodified bovine hemoglobin for 24 h caused no cell injury and a reaction characterized by 48.4 +/- 8.2% increase in 6-keto-PGF1 alpha production, accompanied by 40.2 +/- 9.4% reduction in thromboxane (Tx)B2 (compared with a control group of EC incubated with saline solution). Incubation with a nonpure Hb solution (Hb plus red blood cell membrane aminophospholipids; a-PLs) caused cell injury with significant release of tissue factor, plus a reaction characterized by 97.5 +/- 12.5% increase in TxB2 production accompanied by 25.3 +/- 3% reduction in 6-keto-PGF1 alpha. A second nonpure Hb [Hb plus bacterial environmental endotoxin (E)] caused cell injury, the release of tissue factor, and increased production of both prostaglandins, with greater release of TxB2 (197 +/- 17%) than of 6-keto-PGF1 alpha (112 +/- 8.3%). These data indicate that the endothelium reacts differently to pure and nonpure hemoglobins. The biocompatibility of Hb solutions, with regard to vasoconstriction and activation of intravascular coagulation, depends on the absence of stromal a-PLs and bacterial E.     

Effects of carnitine administration in patients with chronic renal failure undergoing periodic dialysis, evaluated by computerized electromyography

The effects of chronic administration of L-carnitine were evaluated by EMG analysis in 20 uraemic patients undergoing periodical haemodialysis (mean duration of dialysis 34.7 months). No important changes in motor conduction velocity or distal latency of the external popliteal nerve were found after the treatment, while a reduction in the number of polyphasic muscle action potentials was observed. After carnitine administration, an increase of total EMG power was noted and the spectral array showed a progressive shift towards lower frequencies in 8 patients who had shown higher values. These results suggest that carnitine has a prevalent "myotrophic" effect.     

Italian experience with rVIII-single chain: a survey of patients with haemophilia A and their physicians

Journal of Thrombosis and Thrombolysis - rVIII-SingleChain is indicated for treatment and prophylaxis of bleeding in patients with haemophilia A (HA). The safety and efficacy of rVIII-SingleChain...     

Single-center experience of a quadripolar pacing lead for cardiac resynchronization therapy

AIM

Recent studies have shown that a quadripolar left ventricular (LV) lead can result in low rates of dislocation and phrenic nerve stimulation (PNS) acutely and on medium-term follow-up in cardiac resynchronization therapy (CRT). We evaluated the outcomes of CRT patients in whom a quadripolar LV lead was implanted in our institution.

Methods

We studied 45 consecutive heart failure patients (75 % men; age, 70.3?±?9.0 years) following successful implantation of a quadripolar LV lead. Demographic and clinical data were collected preoperatively, and patients were followed up for 18.9 months.

Results

The implantation success rate was 100 %. Mean overall duration was 100.1?±?34.6 min, and X-ray exposure time was 13.20?±?13.5 min. The most distal effective pacing site was used as the final pacing configuration in all patients. Acute dislodgment requiring reoperation occurred before discharge in three cases (6.6 %). Six patients (13 %) suffered PNS during follow-up; we solved this problem by changing the stimulation vector. Three months after implantation, a mean of six out of ten effective sites (threshold <2.5 V at 1.5 ms, no PNS) per patient was recorded.

Conclusions

Over the relatively long term, the quadripolar LV lead was associated with excellent pacing thresholds and low rates of dislocation and PNS.     

Changes in the rheological behavior of the vagina in women with pelvic organ prolapse

Introduction and hypothesis

Pelvic organ prolapse is a common condition impacting the quality of life of millions of women worldwide. Although vaginal estrogen is widely used in women with prolapse, little is known regarding estrogen’s benefits on the biomechanical properties of vaginal tissue. Here, we aimed to examine the effect of prolapse on the biomechanical properties of the vagina and determine alterations in vaginal mechanics in the presence and absence of hormone therapy (HT).

Methods

We characterized the viscoelastic properties of vaginal biopsies from age-matched premenopausal women without (n?=?12) and with prolapse (n?=?8) and postmenopausal women with prolapse on (n?=?18) and off HT (n?=?9). Utilizing a single-lap shear testing protocol, full-thickness anterior vaginal biopsies were subjected to ±10 % shear strain over a range of frequencies (1–90 Hz). This applied energy is either dissipated (viscous) or stored (elastic) as a function of frequency due to compositional or structural differences in the tissue.

Results

Prolapsed tissue was more stiff (higher complex modulus) under shear deformation resulting from increases in both elastic (elastic modulus) and viscous (loss modulus) contributions, with non-prolapsed premenopausal women being the least stiff. Postmenopausal women with prolapse currently on HT were the most stiff of all the groups.

Conclusions

These data suggest that prolapsed tissue has an increased elastic contribution likely resulting from changes in biochemical constituents, and hormones increase the viscous contribution of prolapsed tissue. Overall, this study design characterized the viscoelastic properties of vaginal biopsies and may be utilized to conduct longitudinal studies to better understand the mechanisms of prolapse development and progression.     

From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?

Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.