Plasma levels of pentraxin-3, an acute phase protein, are increased during sickle cell painful crisis

The painful crisis accounts for the majority of sickle cell disease (SCD) related hospital admissions. The prototypic long pentraxin 3 (PTX3), an acute phase protein, is elevated in patients with inflammatory and ischemic states. As the sickle cell painful crisis is associated with both inflammation and tissue ischemia, we questioned whether plasma PTX3 levels are increased during and associated with painful crisis severity. Furthermore, since PTX3 up-regulates endothelial expression of tissue factor we studied PTX levels in relation to markers of endothelial and coagulation activation. Plasma levels of PTX3, ultra-sensitive C-reactive protein (US-CRP), prothrombin fragment 1+2, thrombin-antithrombin (TAT) complexes, von Willebrand Factor antigen and soluble vascular adhesion molecule-1 were determined in 105 asymptomatic sickle cell patients, 33 patients during painful crisis and 30 race matched healthy controls. Plasma PTX3 levels were comparable between patients in asymptomatic state and healthy controls, but significantly higher during painful crisis (P<0.01). US-CRP levels were higher in asymptomatic patients compared to controls (P<0.0001) and increased further during painful crisis (P<0.0001). PTX3 levels at presentation with painful crisis correlated significantly with the duration of subsequent hospital admission (r(s) = 0.43; P = 0.013), whereas US-CRP levels did not. PTX3 levels did not correlate with markers of hypercoagulability. The increase of PTX3 levels during painful crisis and their relation to the duration of subsequent hospital stay suggest that PTX3 might serve both as a diagnostic and severity marker of the painful sickle cell crisis.     

The optimal dose of Adriamycin to create a viable rat model potentially applicable to congenital obstructive uropathy

Purpose

The Adriamycin rat model is an established model for different organ anomalies including congenital obstructive uropathy. In the current study, we carried out a dose-response analysis to find out the optimal dose of Adriamycin to create a viable rat model of obstructive uropathy.

Methods

Thirty time-mated Sprague-Dawley rats were divided into 5 groups including 1 control group and 4 different treatment groups. The 4 Adriamycin dosage regimens investigated in this study were 1.25, 1.5, 1.75, and 2 mg/(kg d). Experimental rats (n = 24) were injected intraperitoneally with different doses of Adriamycin on gestational days 7 to 9 (6 rats in each group). Control rats (n = 6) were injected with an equivalent volume of saline on the same days. Viable term fetuses were harvested on gestational day 21 by cesarean delivery and dissected under a dissecting microscope. Serial transverse sections from urinary tract system were obtained for histological examination.

Results

One hundred thirty-three viable fetuses were recovered from Adriamycin-treated rats, and 50 were from rats in the control group. There were no resorptions in the control group; however, 52 resorptions were recorded in Adriamycin groups. The rates of hydronephrosis and resorptions were 60% and 0%, 80.5% and 5.8%, 100% and 17.3%, and 100% and 76.9% at doses of 1.25, 1.50, 1.75, and 2 mg/(kg d), respectively. Histologic examination of the kidneys in the treated groups showed a significant decrease in renal parenchyma compared with the control group.

Conclusions

The dosage of 1.5 mg/(kg d) of Adriamycin yielded the highest number of viable hydronephrotic fetuses. At this dose, urinary abnormalities are milder; but the highest number of viable fetuses is provided, which is necessary to create a reproducible and viable animal model.     

Evaluation of the vascular anatomy in potential living kidney donors with gadolinium‐enhanced magnetic resonance angiography: comparison with digital subtraction angiography and intraoperative findings

Asgari MA, Dadkhah F, Ghadian AR, Razzaghi MR, Noorbala MH, Amini E. Evaluation of the vascular anatomy in potential living kidney donors with gadolinium‐enhanced magnetic resonance angiography: comparison with digital subtraction angiography and intraoperative findings.
Clin Transplant 2011: 25: 481–485. © 2010 John Wiley & Sons A/S. Abstract: Background: X‐ray contrast arteriography has traditionally been used for pre‐operative evaluation in living kidney donors. However, magnetic resonance angiography (MRA) offers a non‐invasive alternative, which has been considered to be less accurate. This study was performed to determine whether MRA in the pre‐operative investigation of living kidney donors provides sufficient information. Methods: From December 2005 to December 2007, 173 potential live donors were evaluated in this study. Donors performed digital subtraction angiography (DSA) and those with one or more accessory arteries at least on one side recruited for further evaluation with three‐dimensional gadolinium‐enhanced MRA. Results: A total of 30 donors constituted the study population. When compared with DSA as the reference method, MRA detected 20 of 36 renal accessory arteries which indicates a sensitivity of 55.6%. The difference between MRA and DSA in identifying accessory renal arteries was significant (p‐value <0.001). Considering intraoperative findings as the standard of reference, MRA depicted correctly four of six (66.7%) accessory arteries on the transplanted kidneys. Conclusions: MRA has the advantage of avoiding exposure to ionizing radiation and is non‐invasive. These are important considerations in pre‐operative evaluation of a generally healthy donor population. However, MRA provides suboptimal accuracy in detecting small accessory arteries.     

SAR Development of Lysine-Based Irreversible Inhibitors of Transglutaminase 2 for Huntington's Disease

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Effect of Comorbid Depression on Substance Use Disorders

ABSTRACT

The aim of the study was to investigate the effect of depression on pattern of substance use disorders (SUDs). Consecutive samples of (200) Egyptian male SUD inpatients were examined over 1-year period. Study and control samples were chosen. Study group consisted of 30 patients with comorbid substance dependence and depression. Control group consisted of 30 substance-dependent patients without depression. Semistructured interviews, Addiction Severity Index (ASI) and Hamilton Rating Scale for Depression (HDRS), were applied. Comparison between both groups showed significant differences for prescribed opioid use (100% versus 86%), polysubstance use (73% versus 43%), frequency of suicidal attempts (86% versus 43%), mean of admissions to substance use treatment (SUT) units (5 versus 2.2), mean of abstinence periods (3.8 versus 1.2); study group showed greater medical status impairment (P = .05), social and psychiatric impairment (P = .01). It was concluded that depression might affect SUD as regards type of substance used, pattern of use, suicide rate, duration of hospitalization, rate of rehospitalization, and finally medical, social, and psychiatric status impairment.     

Effect of beta-carotene on titanium oxide nanoparticles-induced testicular toxicity in mice

Objective

This study evaluated the protective effect of beta-carotene (BC) on titanium oxide nanoparticle (TNP) induced spermatogenesis defects in mice.

Materials and methods

Thirty-two NMRI mice were randomly divided into four groups. BC group received 10 mg/kg of BC for 35 days. TNP group received 300 mg/kg TNP for 35 days. TNP+BC group initially received 10 mg/kg BC for 10 days and was followed by concomitant administration of 300 mg/kg TNP for 35 days. Control group received only normal saline for 35 days. Epididymal sperm parameters, testicular histopathology, spermatogenesis assessments and testosterone assay were performed for evaluation of the TNP and BC effects on testis.

Results

Serum testosterone levels were markedly decreased in TNP-intoxicated mice. Epididymal sperm parameters including sperm number, motility and percentage of abnormality were significantly changed in TNP-intoxicated mice (p < 0.01). Histopathological criteria such as epithelial vacuolization, sloughing of germ cells and detachment were significantly increased in TNP-intoxicated mice (p < 0.001). BC+TNP treatment significantly prevented these changes (p < 0.05). BC also significantly elevates testosterone levels in BC+TNP group compared to TNP-treated mice (p < 0.01).

Discussion and conclusion

The results of this study demonstrated that BC improved the spermatogenesis defects in TNP-treated mice. BC had a potent protective effect against the testicular toxicity and might be clinically useful.     

Spray-drying enteric polymers from aqueous solutions: A novel, economic, and environmentally friendly approach to produce pH-responsive microparticles

We describe a novel method to fabricate pH-responsive microparticles suitable for oral delivery using an aqueous-based spray-drying approach. The approach involves the neutralization and generation of water-soluble salt forms of enteric polymers. The methacrylic acid polymers (Eudragit L and Eudragit S) were added separately to aqueous solutions of ammonium hydrogen carbonate; the solutions were then spray-dried. FTIR analysis of the harvested microparticle products identified the presence of ammonium methacrylate with the appearance of a peak at 1550 cm⁻¹ corresponding to the stretching of the N–H bond. Incubating the microparticles for three hours at 70 °C and 130 °C for the Eudragit S and L products, respectively, was sufficient to eradicate the ammonium residues. The microparticles, loaded with the model drug prednisolone, were spherical and small in size (2–5 μm). Moreover, the particles were gastro-resistant, and release was rapid and complete at small intestinal conditions. The pH threshold of release of the Eudragit S and Eudragit L microparticles was lowered from 7 and 6 to 6.5 and 5.5, respectively. In bicarbonate media, which are physiological and representative of the conditions of the proximal small intestine (mHanks) and the distal small intestine (Kreb’s), drug release from these spray-dried microparticles was faster compared to microparticles produced from conventional emulsion solvent evaporation methods. This new microparticle preparation concept obviates the need for organic solvents and utilizes spray-drying techniques that are amenable to industrial application; the approach therefore offers economic, safety, and environmental benefits.