Granulocyte transfusions in the management of neutropenic fever: A pediatric perspective

Severe neutropenia-associated invasive bacterial or fungal infections are still the major cause of mortality and morbidity in children receiving cancer chemotherapy. Granulocyte transfusion therapy has been used for many years in the management of neutropenic patients with severe infections in whom the clinical condition deteriorated despite appropriate antimicrobial treatment. Transfused granulocytes can increase the recipient’s blood neutrophil count and accumulation of them into the site of infection. There are some data obtained from retrospective or prospective observational studies in pediatric granulocyte transfusion therapy, but results are not conclusive. This review appraises the potential benefits and risks of the use of granulocyte transfusion in children with neutropenic fever.     

P2X7 receptor antagonist delivery vehicle based on photocrosslinked amphiphilic hybrid gels

We report here a method for the synthesis of a unique hybrid gel system for the sustained delivery of P2X7 receptor (P2X7R) antagonist. P2X7R has been reported as a key mediator in inflammatory processes and controlled delivery of this molecule would be critical for the treatment of inflammatory arthritis. The hybrid gel designed here for the sustained delivery of P2X7R antagonists is based on crosslinked hydrophobic styrene-butadiene-styrene (SBS) polymer as a continuous network, where hydrogel particles prepared with hydrophilic poly(ethylene glycol) (PEG) were embedded into this system. PEG hydrogel particle-incorporated SBS gels were characterized through electron microscopy, water contact angle observations, and strong mechanical properties were confirmed through nanoindentation measurements. The release of P2X7R antagonist from these hybrid hydrogel-elastomer system demonstrated a sustained drug release profile up to 28 days at physiological pH, which was not observed in earlier reports. We obtained drug release percentages ranging from 49.72% to 93.04% which indicated the tunability of release through SBS crosslinking and hydrophilic/hydrophobic nature of SBS. This tunability is significant to achieve simultaneous improvements in drug efficacy with reduced side effects. CellTiter-Glo luminescence measurements using human kidney cells revealed that these networks are non-toxic and highly biocompatible with percent cell viabilities of higher than 85%. The approach presented here with crosslinked, amphiphilic and elastic SBS gel systems is not only promising for extended release of P2X7R antagonist but could also allow for incorporation of different molecules so that simultaneous/sequential and extended release profiles for therapeutic molecules could be achieved.

We report here a method for the synthesis of a unique hybrid gel system for the sustained delivery of P2X7 receptor (P2X7R) antagonist.     

Seroprevalence of tetanus immunity among noninsulin-dependent diabetes mellitus patients

Tetanus is a preventable disease that continues to affect people in both developing and developed countries. The aim of the present study was to evaluate the immunity profile to tetanus in patients with Type II diabetes mellitus (DM) and to compare them with healthy controls. The tetanus antitoxin levels in 310 diabetic patients (104 males and 206 females) and in 200 healthy controls (72 males and 128 females) were measured by ELISA (Virotech, Germany). The mean antitoxin concentration in patient and control groups were 0.8238+/-1.61 and 0.9978+/-1.49 IU/ml, respectively. There was a statistically significant difference between the two groups (z=-3.520, P=.0001 and odds ratio was 2.367). There was a definitive inverse correlation between the duration of diabetes and tetanus antibody titers (Spearman's correlation analysis, r=-.155, P=.006). A gender-dependent difference in the susceptibility to tetanus was present in the diabetic group with antibody titers being significantly higher in males compared with females (z=-2.267, P=.023). For both of control (chi(2)=20.207, P=.003) and patient (chi(2)=43.532, P=.0001) groups, there was a significant inverse correlation between the tetanus immunity levels and age. Statistically, a significant drop in antibody titers of both groups was found as the period past from the last immunization increased (Pearson correlation analysis: for patient group r=-.364, P=.0001; for control group r=-.143, P=.044). The tetanus antitoxin levels were significantly increased in individuals who had primary immunization during childhood (for patient group chi(2)=17.191, P=.0001; for control group chi(2)=9.911, P=.007). A significant reduction in the level of antitoxin immunity to tetanus in association with an increased susceptibility to infections in patients with diabetes may implicate the need for improving vaccination rates in this patient group.     

The Effects of Desflurane on Human Platelet Aggregation In Vitro

In view of the possible antiplatelet effects of general anesthetics, we investigated the in vitro effects of desflurane, a new inhalation agent, on platelet aggregation. For 15 patients who underwent elective operations, blood was sampled with desflurane induction before and after anesthesia but prior to surgery so that platelet aggregation in the drawn blood could be tested before desflurane anesthesia and again after exposure to the anesthetic. Platelet aggregation was measured with a whole-blood aggregometer. Adenosine diphosphate (ADP), collagen, and ristocetin were used as aggregating agents. Our results showed that aggregation in response to ADP, collagen, or ristocetin was not inhibited in patients who received desflurane anesthesia. This study with an in vitro model showed that desflurane had no influence on platelets in clinically relevant doses.     

Protective effects of melatonin against spinal cord injury induced oxidative damage in rat kidney: A morphological and biochemical study

Spinal cord injury (SCI) induced oxidative stress affects multiple organ systems including the kidney. We studied the possible protective effects of melatonin on SCI-induced oxidative damage in renal tissues of rats. Wistar albino rats (n = 24) were exposed to SCI and divided into vehicle- or melatonin-treated SCI groups. Melatonin was administred intraperitoneally at a dose of 10 mg/kg for seven days. Renal tissues were investigated by light and electron microscopy. Furthermore, tissue malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) and superoxide dismutase (SOD) activities were also determined. In the vehicle-treated SCI group, the renal histology was disturbed compared to controls, whereas the melatonin-treated SCI group showed significantly reduced degeneration of renal tissue as seen by both light and electron microscopy. MDA levels, MPO and SOD activities were increased and GSH levels were decreased in the vehicle-treated SCI group compared to controls. On the other hand, decreased MDA levels and MPO activities and increased GSH levels were observed in the melatonin-treated SCI group compared to vehicle-treated SCI group. These results showed that experimentally induced SCI caused oxidative stress in the rat kidney, whereas melatonin treatment reduced oxidative stress, suggesting that it may be used as a complementary therapy of renal problems occurring following SCI.     

Anti-cancer effect of metformin on the metastasis and invasion of primary breast cancer cells through mediating NF-kB activity

Current evidence strongly suggests that aberrant activation of the nuclear factor kappa B (NF-kB) signaling cascade is connected to carcinogenesis. The matrix metalloproteinases (MMP) which are also the key agents for tumor metastasis may be potent candidates for tumor diagnosis in clinics. In this in vitro study, we hypothesized that metformin with an effective dose can inhibit tumor cell proliferation and metastasis by modulating the expressions of MMP-2 and -9 and interfering with NF-kB signaling in primary breast cancer cells (PBCCs). 300 000 cells per ml were obtained from biopsies of breast tumors from five human donors. The cell viability and proliferation were tested. Immunocytochemistry was performed for MMP-2, MMP-9, and NF-kB, and enzyme-linked immunosorbent assay for NF-kB activity, quantitative real-time PCR for RELA/p65, IkBα, MMP-2, and MMP-9. Three different doses of metformin (5, 10, and 25 mM) (Met) reduced the viability and proliferation of PBCCs in a dose-dependent manner, maximum inhibition was observed at 25 mM Met. The expression of RELA/p65 was not affected by 25 mM Met. Nuclear immunoreactivity and activity of NF-kB reduced while cytoplasmic NF-kB (p65) elevated by 25 mM Met compared to non-treatment (P < 0.05). The expression and immunoreactivity of MMP-9 but not MMP-2 were decreased by 25 mM Met treatment, compared with the non-treatment (P < 0.05). Metformin may have an essential antitumor role in the invasion and metastasis pathways of PBCCs by downregulating the MMP-9 expression blocking both the activity and nuclear translocation of NF-kB.