Toxicity of myristic acid analogs toward African trypanosomes.

New drugs are needed for treatment of diseases caused by African trypanosomes. One possible target for chemotherapy is the biosynthesis of the glycosyl phosphatidyl-inositol (GPI) of this parasite's variant surface glycoprotein (VSG). Unlike mammalian GPIs, the diacylglycerol moiety of the VSG anchor contains only myristate (tetradecanoate), added in unique remodeling reactions. We previously found that 11-oxatetradecanoic acid [i.e., 10-(propoxy)decanoic acid] is selectively toxic to trypanosomes. We have now assayed 244 different fatty acid analogs, most with chain lengths comparable to that of myristate, for trypanocidal effects. In these assays we surveyed the effects on toxicity of systematic alterations in the analogs' steric, conformational, and hydrophobic properties. We also used three 3H-labeled oxatetradecanoic acids to explore the mechanism of analog action. Their incorporation into VSG correlated roughly with toxicity, although they also were incorporated into phospholipids and other proteins. Myristate analogs are useful for studying the mechanism of GPI myristolyation, and they are candidates for antitrypanosomal chemotherapy.     

Limitations of Gallium-67 SPECT in histological transformation of chronic lymphocytic leukaemia: an analysis of 13 patients with clinically suspected Richter's syndrome

Gallium-67 single photon emission computerized tomography (Ga-67 SPECT) was performed in 13 chronic lymphocytic leukaemia (CLL) patients suspected of evolution into diffuse large B-cell lymphoma (DLCL) or Richter's syndrome (RS). Six positive and nine negative Ga-67 SPECTs were observed. Ten patients were biopsied (five in each group). DLCL was not detected in any Ga-67-positive patient, including those in whom Ga-67-positive areas were biopsied. The only case of DLCL was demonstrated in a Ga-67-negative patient. The tumoral proliferative index (Ki67 antigen expression) was moderate and similar in both groups of patients. These results illustrate the limitations of Ga-67 SPECT in identifying RS.     

Low-frequency electro-acupuncture and physical exercise improve metabolic disturbances and modulate gene expression in adipose tissue in rats with dihydrotestosterone-induced polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity, and insulin resistance. Pharmacotherapy is often unsatisfactory. This study evaluates the effects of low-frequency electro-acupuncture (EA) and physical exercise on metabolic disturbances and adipose tissue mRNA expression of selected genes in a rat PCOS model characterized by insulin resistance and adiposity. Dihydrotestosterone (inducing PCOS) or vehicle (control) was administrated continuously, beginning before puberty. At age 10 wk, PCOS rats were randomly divided into three groups; PCOS, PCOS EA, and PCOS exercise. PCOS EA rats received 2-Hz EA (evoking muscle twitches) three times/wk during 4-5 wk. PCOS exercise rats had free access to a running wheel for 4-5 wk. EA and exercise improved insulin sensitivity, measured by clamp, in PCOS rats. Exercise also reduced adiposity, visceral adipocyte size, and plasma leptin. EA increased plasma IGF-I. Real-time RT-PCR revealed increased expression of leptin and IL-6 and decreased expression of uncoupling protein 2 in visceral adipose tissue of PCOS rats compared with controls. EA restored the expression of leptin and uncoupling protein 2, whereas exercise normalized adipose tissue leptin and IL-6 expression in PCOS rats. Thus, EA and exercise ameliorate insulin resistance in rats with PCOS. This effect may involve regulation of adipose tissue metabolism and production because EA and exercise each partly restore divergent adipose tissue gene expression associated with insulin resistance, obesity, and inflammation. In contrast to exercise, EA improves insulin sensitivity and modulates adipose tissue gene expression without influencing adipose tissue mass and cellularity.     

Clinical outcomes in outpatient respiratory syncytial virus infection in immunocompromised children

Background

Immunocompromised patients are at high risk for morbidity and mortality due to respiratory syncytial virus (RSV) infection. Increasingly, pediatric patients with malignancy or undergoing transplantation are managed primarily as outpatients. Data regarding the clinical presentation and outcomes of RSV in the outpatient pediatric immunocompromised population are limited.

Methods

We performed a retrospective cohort study of children with hematologic malignancy or hematopoietic or solid organ transplant with laboratory‐confirmed RSV infection diagnosed as outpatients at an academic medical center between 2008 and 2013.

Results

Of 54 patients with RSV detected while outpatients, 15 (28%) were hospitalized, 7 (13%) received ribavirin, and one (2%) received intravenous immunoglobulin. One (2%) patient was critically ill, but there were no deaths due to RSV infection. Fever (P < 0·01) was associated with increased risk of hospitalization.

Conclusions

Most immunocompromised children with RSV detected while outpatients did not require hospitalization or receive antiviral treatment. Potential studies of RSV therapies should consider inclusion of patients in an ambulatory setting.     

Lipid peroxidation is enhanced in patients with systemic lupus erythematosus and is associated with arterial and renal disease manifestations

OBJECTIVE: Cardiovascular disease with premature atherosclerosis is common in patients with systemic lupus erythematosus (SLE). We previously identified elevated levels of oxidized low-density lipoprotein (OxLDL) together with elevated levels of autoantibodies related to OxLDL as risk factors for cardiovascular disease in female patients with SLE. Autoantibodies to OxLDL are common in SLE and cross-react with anticardiolipin antibodies (aCL). We therefore hypothesized that lipid peroxidation is enhanced in patients with SLE in general. METHODS: One hundred forty-seven female patients with SLE and 60 age- and sex-matched controls were compared. A monoclonal antibody to oxidized phospholipids, EO6, was used to determine oxidation epitopes on LDL. Anti-OxLDL and autoantibodies to malondialdehyde (MDA)-modified LDL, cardiolipin, and oxidized aCL were determined by chemiluminescence technique. RESULTS: As determined by binding of EO6, patients with SLE had a higher level of oxidized phospholipids on LDL (P = 0.005) compared with controls. The level of OxLDL (e.g., oxidized phospholipid/apolipoprotein B) was associated with arterial disease (P = 0.006) and renal manifestations (P = 0.04). As reported previously, levels of aCL, autoantibodies to OxLDL, and autoantibodies to MDA-modified LDL were enhanced and were closely correlated in SLE. Anticardiolipin antibodies from these SLE patients recognized mainly oxidized forms of cardiolipin, indicating that antigenic epitopes on cardiolipin are related to lipid peroxidation in patients with SLE. CONCLUSION: In general, patients with SLE (particularly those with cardiovascular disease) had more oxidized epitopes on LDL compared with controls. Furthermore, aCL in these patients recognized epitopes generated during lipid peroxidation. Thus, "neo" self antigens on lipoproteins, generated during oxidation, are present in SLE and may be of importance for the development of premature cardiovascular disease and possibly also for other autoimmune phenomena observed in SLE.     

Biomechanical comparison of double grasping repair versus cross-locked cruciate flexor tendon repair

Purpose

This study was conducted to compare the in vitro biomechanical properties of tensile strength and gap resistance of a double grasping loop (DGL) flexor tendon repair with the established four-strand cross-locked cruciate (CLC) flexor tendon repair, both with an interlocking horizontal mattress (IHM) epitendinous suture. The hypothesis is that the DGL-IHM method which utilizes two looped core sutures, grasping and locking loops, and a single intralesional knot will have greater strength and increased gap resistance than the CLC-IHM method.

Methods

Forty porcine tendons were evenly assigned to either the DGL-IHM or CLC-IHM group. The tendon repair strength, 2-mm gap force and load to failure, was measured under a constant rate of distraction. The stiffness of tendon repair was calculated and the method of repair failure was analyzed.

Results

The CLC-IHM group exhibited a statistically significant greater resistance to gapping, a statistically significant higher load to 2-mm gapping (62.0 N), and load to failure (99.7 N) than the DGL-IHM group (37.1 N and 75.1 N, respectively). Ninety percent of CLC-IHM failures were a result of knot failure whereas 30 % of the DGL-IHM group exhibited knot failure.

Conclusions

This study demonstrates that the CLC-IHM flexor tendon repair method better resists gapping and has a greater tensile strength compared to the experimental DGL-IHM method. The authors believe that while the DGL-IHM provides double the number of sutures at the repair site per needle pass, this configuration does not adequately secure the loop suture to the tendon, resulting in a high percentage of suture pullout and inability to tolerate loads as high as those of the CLC-IHM group.     

Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children

Please cite this paper as: Martin et al. (2012) Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children. Influenza and Other Respiratory Viruses 6(1), 71–77. Background Molecular testing for viral pathogens has resulted in increasing detection of multiple viruses in respiratory secretions of ill children. The clinical impact of multiple virus infections on clinical presentation and outcome is unclear. Objectives To compare clinical characteristics and viral load between children with multiple virus versus single virus illnesses. Patients/methods Eight hundred and ninety‐three residual nasal wash samples from children treated for respiratory illness at Children’s Hospital, Seattle, from September 2003 to September 2004 were evaluated by quantitative PCR for respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (Flu), parainfluenza, adenoviruses, and coronaviruses (CoV). Illness severity and patient characteristics were abstracted from medical charts. Results Coinfections were identified in 103 (18%) of 566 virus‐positive samples. Adenovirus was most commonly detected in coinfections (52%), followed by CoV (50%). Illnesses with a single virus had increased risk of oxygen requirement (P = 0·02), extended hospital stays (P = 0·002), and admissions to the inpatient (P = 0·02) or intensive care units (P = 0·04). For Adv and PIV‐1, multiple virus illnesses had a significantly lower viral load (log₁₀ copies/ml) than single virus illnesses (4·2 versus 5·6, P = 0·007 and 4·2 versus 6·9, P < 0·001, respectively). RSV, Flu‐A, PIV‐3, and hMPV viral loads were consistently high whether or not another virus was detected. Conclusions Illnesses with multiple virus detections were correlated with less severe disease. The relationship between viral load and multiple virus infections was virus specific, and this may serve as a way to differentiate viruses in multiple virus infections.     

Measurement of leg length discrepancy after total hip arthroplasty. The reliability of a plain radiographic method compared to CT-scanogram

Objective  

To measure the interobserver reliability and intraobserver reproducibility of post total hip arthroplasty (THA) leg length discrepancy (LLD) measurement on radiographs as well as to evaluate its accuracy by comparing it with LLD measurement on computed tomographic scanogram (CT-scanogram).     

Interaction between the functional SNP rs2070951 in NR3C2 gene and high levels of plasma corticotropin-releasing hormone associates to postpartum depression

Archives of Women's Mental Health - Postpartum depression (PPD) is a common mood disorder that occurs after delivery with a prevalence of approximately 10%. Recent reports have related...