Protection of murine bone marrow by dexamethasone during cytotoxic chemotherapy

Corticosteroids have the ability to suppress the production of growth factors and cytokines and are thus implicated in the negative regulation of hematopoiesis. We have shown that the corticosteroids, prednisolone and dexamethasone, were able to effectively protect progenitor cells in four strains of mice against cell-cycle-specific antimetabolic chemotherapy agents. The highest levels of protection against 5-fluorouracil (FU; 200 mg/kg) were achieved when two or three intraperitoneal injections of dexamethasone were administered between - 7 and +3 hours at a dose of 7.5 mg/kg/injection (optimal dose) or by continuous infusion between -4 and +20 hours. This protective effect is manifested as an increase in the number of high proliferative potential colony-forming cells that survive in the bone marrow 3 days after treatment with FU from between 0.5% and 11% to between 10% and 34% of normal. The bone marrow progenitors and blood cell numbers return to normal from 3 to 5 days and 1 to 2 days earlier, respectively. Less dexamethasone than prednisolone is required to give an equivalent protective effect, which is consistent with their anti-inflammatory potency. These findings are further evidence of the negative regulatory role played by corticosteroids, and indicate that the treatment schedules of corticosteroids during cancer therapy need to be reexamined to obtain the maximum benefit from their use.     

Conjugated dihydroxy bile salt inhibition of glucose influx in rat jejunumin vitro

Effects of bile salts on intestinal glucose transfer differ in diverse animal preparations exposed to various bile acids. Radiolabeled glucose influx into rat jejunum in vitro was studied in buffer and compared to taurodeoxycholate, taurochenodeoxycholate, taurocholate, and deoxycholate. Jejunum was obtained from intact, bile-diverted, and colestipoltreated rats and in similar categories after abdominal x-irradiation. Taurodeoxycholate but not taurocholate inhibited glucose influx only in bile-fistula and colestipol-treated rats. Bile diversion increased and colestipol decreased glucose uptake from buffer. Added inhibitory effects of irradiation and bile salts were seen in bile-fistula animals. These data suggest that normal exposure to bile is chronically inhibiting jejunal glucose transport and that dihydroxy bile salts are responsible for this effect. They do not provide an explanation for the role of bile in the intestinal radiation syndrome.This work was supported in part by contract No. AT-(40-1) 3882 from the U.S. Atomic Energy Commission.These data were presented in part at the annual meeting of the Southern Society for Clinical Investigation, New Orleans, La. February, 1975.     

Structural study and large magnetocaloric entropy change at room temperature of La1−x□xMnO3 compounds

In this study, our central focus is to investigate the magnetocaloric characteristics of a La_1−x□_xMnO₃ (x = 0.1, 0.2 and 0.3) series prepared by a sol–gel technique published in Prog. Mater. Sci., 93, 2018, 112–232. The crystallographic study revealed that our compounds crystallize in a rhombohedral structure with R$\bar{3}$c. Ferromagnetic (FM) and paramagnetic (PM) characters were detected from the variation in magnetization as a function of magnetic fields at different temperatures. The second order transition was verified from the Arrott plots (M²vs. (μ₀H/M)), where the slopes have a positive value. In order to verify the second order, we traced the variation of magnetization vs. temperature at different magnetic fields for x = 0.2. This revealed a ferromagnetic (FM)–paramagnetic (PM) transition when temperature increases. Relying on the indirect method while using the Maxwell formula, we determined the variation in the entropy (−ΔS_M) as a function of temperature for different magnetic fields for the three samples. We note that all the studied systems stand as good candidates for magnetic refrigeration with relative cooling power (RCP) values of around 131.4, 83.38 and 57.26 J kg⁻¹ with magnetic fields below 2 T, respectively. Subsequently, the magnetocaloric effect was investigated by a phenomenological model for x = 0.2. The extracted data confirm that this phenomenological model is appropriate for the prediction of magnetocaloric properties. The study also demonstrated that this La_0.8□_0.2MnO₃ system exhibits a universal behaviour.

In this study, our central focus is to investigate the magnetocaloric characteristics of a La_1−x□_xMnO₃ (x = 0.1, 0.2 and 0.3) series prepared by a sol–gel technique.     

Structural,optical and dielectric properties of Cu1.5Mn1.5O4 spinel nanoparticles

In this study, a Cu_1.5Mn_1.5O₄ spinel was successfully synthesized by a sol–gel method at 500 °C for 5 h and characterized by different techniques. X-ray diffraction (XRD), Fourier transformation infrared (FTIR) spectroscopy and Raman spectroscopic analyses confirmed the formation of a spinel cubic structure with the Fd$\bar{3}$m space group. The SEM proves that the grain size of our compound is of the order of 48 nm. Crystallite sizes determined from three estimates are closer to the grain size obtained from the SEM, indicating the single domain nature of the sample. The optical properties of UV-visible spectroscopy for our sample showed that the gap value is equal to 3.82 eV, making our compound a good candidate for optoelectronic applications. For electrical properties, impedance spectroscopy was performed at a frequency range of 40 ≤ frequency ≤ 10⁶ Hz. This suggested hoping conduction due to three theoretical models. The latter can be attributed to the correlated barrier hopping (CBH) model in region I, overlapping large polaron tunneling (OLPT) in region II and non-overlapping small polaron tunneling (NSPT) mechanism in region III. One dielectric relaxation is detected from the dielectric impedance and modulus, attributed to grain contributions. This behavior was confirmed by both Nyquist and Argand''s plots of dielectric impedance at different measuring temperatures.

In this study, a Cu_1.5Mn_1.5O₄ spinel was successfully synthesized by a sol–gel method at 500 °C for 5 h and characterized by different techniques.     

Gastric Stenosis After Laparoscopic Sleeve Gastrectomy: Diagnosis and Management

Purpose

The use of laparoscopic sleeve gastrectomy (LSG) is increasing worldwide. Although post-LSG gastric stenosis (GS) is less frequent, it has not been well defined and lacks standardized management procedures. The objective of the present study was to describe a series of patients with GS symptoms after LSG and to develop a standardized management procedure for this complication.

Methods

We performed a retrospective analysis of a prospective database of patients presenting with GS after LSG procedures performed between January 2008 and March 2014. The primary efficacy criterion was the frequency of post-LSG GS. GS was classified as functional (i.e. a gastric twist) or organic. The secondary efficacy criteria included the time interval between LSG and diagnosis of GS, the type of stenosis, the type of management, and the follow-up data.

Results

During the study period, 1210 patients underwent primary or secondary LSG. Seventeen patients had post-operative symptoms of GS (1.4 %); one patient had achalasia that had not been diagnosed preoperatively and thus was excluded from our analysis. The median time interval between LSG and diagnosis of GS was 47.2 days (1–114). Eleven patients had organic GS and six had functional GS. Seven patients required nutritional support. Endoscopic treatment was successful in 15 patients (88.2 %) after balloon dilatation (n?=?13) or insertion of a covered stent (n?=?2). Two of the 15 patients required conversion to Roux-en-Y gastric bypass (11.8 %).

Conclusion

GS after LSG is a rare complication but requires standardized management. Most cases can be treated successfully with endoscopic balloon dilatation.

     

Autoantibody against erythrocyte protein 4.1 in a patient with autoimmune hemolytic anemia

We observed the presence of a new autoantibody, anti-erythrocyte protein 4.1, in a patient with autoimmune hemolytic anemia (AIHA). Western blotting analysis revealed that IgG from the patient's plasma reacted with erythrocyte protein 4.1. However, among other patients with hemolytic diseases (six having AIHA and three each having either hereditary spherocytosis, elliptocytosis, or lead poisoning) as well as among control subjects, no antibody activity to protein 4.1 was observed. In addition to the anti-protein 4.1 antibody, two different kinds of anti-erythrocyte antibodies were detected by conventional serological studies in this patient. One of them was an anti-Ena-like antibody in the eluate from the patient's erythrocytes, while another was the anti-S-specific antibody in the plasma. An elution study and an absorption study using S antigen-positive erythrocytes demonstrated that the anti-protein 4.1 antibody differed from both the anti-Ena-like antibody and the anti-S antibody. Familial analysis of the patient revealed the same antibody in her brother, who did not have hemolytic anemia. These results demonstrate that anti-protein 4.1 antibody is considered to be included in the spectrum of anti-cytoskeleton autoantibodies, which have been observed in patients having increased cell lysis as well as in healthy subjects.     

Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukemia (CML) contribute to relapse after autologous bone marrow in CML

Relapse after autologous bone marrow transplantation for chronic myelogenous leukemia (CML) can be due either to the persistence of leukemia cells in systemic tissues following preparative therapy, or due to the persistence of leukemia cells in the autologous marrow used to restore marrow function after intensive therapy. To help distinguish between these two possible causes of relapse, we used safety-modified retroviruses, which contain the bacterial resistance gene NEO, to mark autologous marrow cells that had been collected from patients early in the phase of hematopoietic recovery after in vivo chemotherapy. The cells were then subjected to ex vivo CD34 selection following collection and 30% of the bone marrow were exposed to a safety-modified virus. This marrow was infused after delivery of systemic therapy, which consisted of total body irradiation (1,020 cGy), cyclophosphamide (120 mg/kg), and VP-16 (750 mg/m2). RT PCR assays specific for the bacterial NEO mRNA, which was coded for by the virus, and the bcr-abl mRNA showed that in two evaluable CML patients transplanted with marked cells, sufficient numbers of leukemia cells remained in the infused marrow to contribute to systemic relapse. In addition, both normal and leukemic cells positive for the retroviral transgenome persisted in the systemic circulation of the patients for at least 280 days posttransplant showing that the infused marrow was responsible for the return of hematopoiesis following the preparative therapy. This observation shows that it is possible to use a replication-incompetent safety-modified retrovirus in order to introduce DNA sequences into the hematopoietic cells of patients undergoing autologous bone marrow transplantation. Moreover, this data suggested that additional fractionation procedures will be necessary to reduce the probability of relapse after bone marrow transplantation in at least the advanced stages of the disease in CML patients undergoing autologous bone marrow transplantation procedures.