Impaired branched chain amino acid metabolism alters feeding behavior and increases orexigenic neuropeptide expression in the hypothalamus

Elevation of dietary or brain leucine appears to suppress food intake via a mechanism involving mechanistic target of rapamycin, AMPK, and/or branched chain amino acid (BCAA) metabolism. Mice bearing a deletion of mitochondrial branched chain aminotransferase (BCATm), which is expressed in peripheral tissues (muscle) and brain glia, exhibit marked increases in circulating BCAAs. Here, we test whether this increase alters feeding behavior and brain neuropeptide expression. Circulating and brain levels of BCAAs were increased two- to four-fold in BCATm-deficient mice (KO). KO mice weighed less than controls (25·9 vs 20·4?g, P<0·01), but absolute food intake was relatively unchanged. In contrast to wild-type mice, KO mice preferred a low-BCAA diet to a control diet (P<0·05) but exhibited no change in preference for low- vs high-protein (HP) diets. KO mice also exhibited low leptin levels and increased hypothalamic Npy and Agrp mRNA. Normalization of circulating leptin levels had no effect on either food preference or the increased Npy and Agrp mRNA expression. If BCAAs act as signals of protein status, one would expect reduced food intake, avoidance of dietary protein, and reduction in neuropeptide expression in BCATm-KO mice. Instead, these mice exhibit an increased expression of orexigenic neuropeptides and an avoidance of BCAAs but not HP. These data thus suggest that either BCAAs do not act as physiological signals of protein status or the loss of BCAA metabolism within brain glia impairs the detection of protein balance.     

Immunomodulatory activity of a protein isolated from garlic extract on delayed type hypersensitivity

Garlic is known as a potent spice and a medicine with broad therapeutic properties ranging from antibacterial to anticancer, and anticoagulant. One major protein has been isolated and purified; it is the 14-kDa glycoprotein. This protein has shown to have immunomodulatory effects. In this study, two sources of garlic (freshly prepared and commercial tablet) were used. Both sources of garlic were augmented delayed type hypersensitivity (DTH) response, the optimum enhancement were detected at 20 mg/kg. Histological studies indicate that 20 mg/kg caused a hyperplasia and hypertrophy of periarteriolar lymphoid sheath of spleen and paracortical zone of lymph nodes. Partial purified fraction could increase the DTH response comparing to garlic extract, and purified protein could highly increase the DTH response comparing to both garlic extract and partial purified fraction. Garlic at all doses employed did not exhibit any effect on enhancement of antibody titer to SRBC.     

Phosphatidylinositol 3‐kinases inhibitor LY294002 potentiates the cytotoxic effects of doxorubicin,vincristine, and etoposide in a panel of cancer cell lines

Many novel therapeutic approaches to overcome chemoresistance have involved targeting specific signaling pathways such as the phosphatidylinositol 3‐kinase (PI3K) pathway. PI3K is a known stress response pathway which is involved in the regulation of cell survival, apoptosis, and growth. Inhibition of this pathway may possibly restore or augment the effectiveness of chemotherapy. Using three human malignant cell lines, we examined the effects of LY294002 (PI3K inhibitor) on chemotherapeutic agent‐induced apoptosis and cytotoxicity. An antimicrotubule agent vincristine, a topoisomerase II inhibitor etoposide, and a DNA cross‐linking agent doxorubicin were used accompanied with LY294002. Cell viability was determined by MTT assay, and the induction of apoptosis was assessed by immunoblotting of caspase‐3. Blocking the PI3K/Akt cascade with a PI3K inhibitor LY294002 (10 μM) increased the cytotoxic effect of vincristine and doxorubicin on SK‐OV‐3 cell line. Furthermore, LY294002 showed a greater promoting effect in etoposide‐ and doxorubicin‐induced cytotoxicity on MDA‐MB‐468 and A549 cells. The quantity of cleaved caspase‐3 in cancer cells that had combination therapy was increased compared with that in the cells treated with each drug alone. We suggest that inhibitors of the PI3K/Akt pathway in combination with chemotherapeutic agents may induce cell death effectively and be a potent modality to treat various types of cancer. The effectiveness of such combination therapy is depending to the used cell line and class of anticancer drug.     

Prevalence of type I allergy to natural rubber latex and type IV allergy to latex and rubber additives in operating room staff with glove-related symptoms.

There is lack of data on the prevalence of latex allergy in the health care setting in Iran. This study was performed to determine the prevalence of type I latex allergy and type IV allergy to latex and rubber additives among the operating room staff with glove-related symptoms in 13 general hospitals in Tehran. Skin-prick tests with commercial latex extract, patch tests with latex and 25 rubber additive series, and total and latex-specific IgE detection were performed on the operating room staff who reported latex glove-related symptoms. Five hundred twelve self-administered questionnaires (100%) were completed by all operating room staff and latex glove-related symptoms were reported by 59 (11.5%) employees. Among all symptomatic operating room staff tested, the prevalence of type I latex allergy was 30.5% and the prevalence rates of type IV allergy to latex and rubber additives were 16.7 and 14.6%, respectively. The most positive patch test result with rubber additives was related to tetramethylthiuram monosulfide (38.5%). The risk factors for type I latex allergy were female sex (p = 0.009) and positive patch test with rubber additives (p = 0.012). Subjects who had positive patch test with latex were significantly more likely to have positive patch test with rubber additives (p < 0.0001). Our results showed a high prevalence of type I latex allergy and type IV allergy to latex and rubber additives. Based on this study, we recommend eliminating powdered latex gloves from the operating rooms of the 13 studied general hospitals and support the substitution of powder-free latex gloves.     

Nintinol self-expandable metallic stenting in management of malignant obstructive jaundice: a case series

Background and Aims

Palliation therapy is the only available therapeutic method for most patients with tumor-induced obstructive jaundice. Metallic stents are now performed percutaneously as an alternative route to the endoscopic approach. It is widely accepted because of its safety, good patency rate, and minimal invasiveness. This study was designed to evaluate the long-term results of metallic self-expandable stent insertion in patients with malignant stenosis of the biliary tree.

Methods

It is a longitudinal study of patients with percutaneously biliary stenting from September 2005 to March 2009. The patients had unresectable malignant biliary obstruction with unsuccessful endoscopic stenting and access. Percutaneous transhepatic cholangiogram performed after adequate local anesthesia, under sonographic or fluoroscopic guidance. Stenting or balloon dilation was performed through the hydrophilic guide wire. Among 50 patients, 45 stents were placed in biliary tree stenosis sites. Patients’ follow-up was during the first, second, third, and then the sixth month after insertion of biliary stents. Stent patency was considered successful in our patients, when there were no lab results or sonographic appearance of biliary tree obstruction.

Results

10(20%) patients’ stent placement treatment failed because of unsuccessful technical procedure. The stenosis of biliary tract was complete and passage of guide wire was not possible through the tumor growth. 6 (15 %) patients with successful stent placements died within one month (mean, 22 days). Total serum bilirubin resolved to below 1.5 mg/dl within 30 days for 36 (90%) patients with successful stent placements. Early complications not leading to death occurred in 28% of cases. The mean survival time for all patients who underwent stent placement was 140 days (16-420days). The mean patency rate for all stents was 147 days.

Conclusions

Percutaneous biliary stenting is a safe procedure with few technical complications and a high success rate of palliation for patients with malignant biliary jaundice. Early complications are mostly managed conservatively and death is mainly due to systemic effects of the malignant disease.     

X-ray Diffraction Analysis and Williamson-Hall Method in USDM Model for Estimating More Accurate Values of Stress-Strain of Unit Cell and Super Cells (2 × 2 × 2) of Hydroxyapatite,Confirmed by Ultrasonic Pulse-Echo Test

Taking into account X-ray diffraction, one of the well-known methods for calculating the stress-strain of crystals is Williamson-Hall (W–H). The W-H method has three models, namely (1) Uniform deformation model (UDM); (2) Uniform stress deformation model (USDM); and (3) Uniform deformation energy density model (UDEDM). The USDM and UDEDM models are directly related to the modulus of elasticity (E). Young’s modulus is a key parameter in engineering design and materials development. Young’s modulus is considered in USDM and UDEDM models, but in all previous studies, researchers used the average values of Young’s modulus or they calculated Young’s modulus only for a sharp peak of an XRD pattern or they extracted Young’s modulus from the literature. Therefore, these values are not representative of all peaks derived from X-ray diffraction; as a result, these values are not estimated with high accuracy. Nevertheless, in the current study, the W-H method is used considering the all diffracted planes of the unit cell and super cells (2 × 2 × 2) of Hydroxyapatite (HA), and a new method with the high accuracy of the W-H method in the USDM model is presented to calculate stress (σ) and strain (ε). The accounting for the planar density of atoms is the novelty of this work. Furthermore, the ultrasonic pulse-echo test is performed for the validation of the novelty assumptions.     

Mechanical Characteristics of Cement Paste in the Presence of Carbon Nanotubes and Silica Oxide Nanoparticles: An Experimental Study

Considering the remarkable characteristics of nanomaterials, previous research studies investigated the effects of incorporating different types of these materials on improving the concrete properties. However, further studies are required to evaluate the complementary hybridization and synergistic influence of nanomaterials. In this research, the combined effect of adding nano silica particles (NS) and multi-walled carbon nanotubes (MWCNT) on enhancing both the compressive and flexural strengths of the cement paste was investigated. Moreover, the morphology of the interface between cement paste and aggregates was studied by scanning electron microscopy (SEM). The mixtures were prepared using three different portions of MWCNT and NS. Electron microscopy images indicated a uniform distribution of nanoparticles in the cement matrix, enhanced hydration reactions, and increased density. Based on the experiments’ outcomes, the combined utilization of silica and carbon nanomaterials in the cement paste did not necessarily result in the maximum compressive and flexural strengths. Furthermore, it was observed that the use of higher percentages of pristine NS in the absence of MWCNT can lead to further enhancement of strength properties of the cement paste.     

Hepatitis C virus (HCV) Infection Rate among Seronegative Hemodialysis Patients Screened by Two Methods; HCV Core Antigen and Polymerase Chain Reaction

Background

End-stage renal disease patients on chronic hemodialysis are among high risk groups for hepatitis C virus (HCV) infection for whom routine HCV screening is recommended. Anti-HCV antibody (ab) testing may not be reliable to detect all infected cases because of the blunted ab response due to depressed immune state in these patients. Using a more reliable, cost-effective and non-complex HCV screening test may be necessary in this group of patients for case finding and management, and also for prevention of infection spread.

Objectives

The aim of this study was to find the prevalence of HCV infection in HCV ab negative hemodialysis patients by Real time PCR and total HCV core antigen (ag) test and comparing the results of the two tests.

Patients and Methods

From a single hemodialysis center, 181 anti- HCV ab negative patients were screened by total HCV core ag using an ELISA kit. Real time PCR was used for determination of the virus and viral load quantity.

Results

Among the 181 anti-HCV ab negative patients, 13 (7.2%) were positive for HCV core ag and 11 (6%) had detectable HCV RNA with a range of 40-336543 IU/ml by PCR. The two tests had a high measurement agreement (Kappa=0.82, P<0.001). Of the 13 patients with positive HCV core ag test results, 3 were negative for HCV RNA. Considering real time PCR for HCV RNA as the gold standard for HCV infection determination in this patient population, HCV core ag assay yielded a sensitivity of 90.9%, specificity of 98.2%, positive predictive value of 76.9% and negative predictive value of 99.4%.

Discussion

The rate of HCV infection among HCV ab negative hemodialysis patients was high. HCV core ag testing could be used as a sensitive method for HCV infection screening in this group of patients.     

Prolonging androgen sensitivity in prostate cancer – a role for COX inhibitors?

Background: Advanced prostate cancer has long been known to respond to androgen deprivation, but disease inevitably progresses to become androgen independent. Lengthening the responsive period is an important, yet underinvestigated, clinical goal. This study aims to determine whether cyclooxygenase‐2 (COX‐2) inhibitors are potentially useful agents in prolonging androgen sensitivity. Methods: The expression of COX‐2 in human prostate surgical specimens, both benign and malignant, androgen dependent and independent, was determined by immunohistochemistry. Nude mice, in which prostate cancer xenografts had been established, were castrated and randomized to receive either COX‐2 inhibitor or vehicle for 8 weeks. Time to androgen independence (AIPC), growth rate and rate of PSA rise were compared between groups. COX‐2 expression, at the mRNA and protein level, was determined in the native xenograft cell line and in tissues of varying androgen sensitivity derived from the xenografts. Results: In human tissues, COX‐2 protein was expressed in prostate epithelium and was upregulated in prostate cancer and remained upregulated after androgen ablation and in the androgen‐independent state. Tissue obtained from the LNCaP xenograft model showed variable COX‐2 expression, with some evidence of downregulation in AIPC. The addition of a COX‐2 inhibitor to castration does not lengthen the time to AIPC (P= 0.53), rate of tumour growth (P= 0.59) or rate of PSA rise (P= 0.34) in the LNCaP xenograft model. Conclusion: This study does not support a role for COX‐2 inhibitors in prolonging androgen responsiveness in prostate cancer.     

The role of mild treadmill exercise on spatial learning and memory and motor activity in animal models of ibotenic acid-induced striatum lesion

Purpose

The basal ganglia have long been implicated in motor and cognitive function. Previous research has shown that regular forced treadmill running improves cognitive performance especially learning and memory. In this study, we examined the role of mild forced treadmill exercise on spatial learning and memory, and motor activity.

Methods

56 male Wistar rats were randomly split into seven groups. Animals received ibotenic acid infusions into striatum bilaterally. Spatial learning and memory for all rats were evaluated by Morris water maze test. On the following day, visible and probe tests were performed for all groups. Motor activity of rats was assessed by open-field apparatus.

Results

Our results showed that animals with striatal lesion were much slower at finding the platform. Mild treadmill exercise during training could decrease the distance traveled to find the hidden platform. While exercise has shown to improve learning/memory, it has not been able to completely treat the impairment caused by ibotenic acid injection into the striatum. Results of open-field test were congruent with the Morris water maze test, with exercise animals displaying higher levels of motor activity.

Conclusions

The present results suggest that striatum has a critical role in spatial learning and memory. However, mild treadmill exercise could not improve impaired spatial learning and memory in rats with striatum lesion.