Malnutrition–Inflammation Complex Syndrome and Hepatitis C in Maintenance Hemodialysis Patients

Protein-energy malnutrition and inflammation are among the leading causes of poor outcome in hemodialysis patients. Hepatitis C virus (HCV) infection is accompanied by elevated proinflammatory mediators, also found in dialysis patients with malnutrition–inflammation complex syndrome. We aimed to study the rate and characteristics of malnutrition–inflammation complex syndrome (MICS) in hemodialysis patients, especially those with hepatitis C. The study included 147 patients (mean age 55.1 ± 12.9 years), 24.5% of whom were HCV-positive, undergoing adequate hemodialysis three times a week for the last 52.7 ± 52.5 months. Parameters of nutrition and inflammation were investigated to evaluate MICS. HCV-positive vs. HCV-negative patients had significantly higher hematocrit (29.6 ± 4.5 g/dL vs. 28.1 ± 4.3, P < 0.05), uric acid (345.8 ± 96.5 vs. 321.3 ± 118.8 µmol/mL, P < 0.05), aspartate aminotransferase (AST, also known as serum glutamic oxaloacetic transaminase [SGOT]) (23.3 ± 14.9 vs. 17.8 ± 9 U/L, P < 0.008), alanine aminotransferase (ALT, also known as serum glutamic pyruvic transaminase [SGPT]) (41.2 ± 28.7 vs. 26.6 ± 17.1 U/L, P < 0.0003), serum creatinine (980.4 ± 219.1 vs. 888.4 ± 202.9 µmol/mL, P < 0.022), intact parathyroid hormone (329.7 ± 630.5 vs. 110.2 ± 145.3 pg/mL, P < 0.002), malnutrition–inflammation score (7.4 ± 5.2 vs. 5.6 ± 4.1, P < 0.038), and Charlson comorbidity index (4.5 ± 1.5 vs. 4 ± 1.4, P < 0.05). MICS had a prevalence of 20–40% in our study. HCV-positive patients had a significantly higher prevalence of MICS than HCV-negative patients (30–40% vs. 20–30%).     

A comparison of the antinociceptive and temperature responses to morphine and fentanyl derivatives in rats

In addition to producing antinociception, opioids exert profound effects on body temperature. This study aimed at comparing antinociceptive and hyperthermic responses between two groups of μ-opioid receptor agonists: fentanyl (4-anilinopiperidine-type) and morphine (phenanthrene-type) derivatives in rats. Analgesic activity was assessed by tail immersion test and the body temperature by insertion of a thermometer probe into the colon. Fentanyl (F), (±)-cis-3-methyl fentanyl (CM), (±)-cis-3-carbomethoxy fentanyl (C), (±)trans-3-carbomethoxy fentanyl (T) and (±)-cis-3 butyl fentanyl (B) produced dose-dependent increase in antinociception and hyperthermia. The relative order of analgesic potency was: CM(11.27)>F(1)>C(0.35)≥T(0.11)≥B(0.056). Similar to this, the relative order of hyperthermic potency was: CM(8.43)>F(1)>C(0.46)≥T(0.11)≥B(0.076). Morphine (M), oxycodone (O), thebacon (T) and 6,14-ethenomorphinan-7-methanol, 4,5-epoxy-6-fluoro-3-hydroxy-α,α,17-trimethyl-, (5α,7α) (E) also produced dose-dependent increase in antinociception and hyperthermia. Among morphine derivatives the relative order of analgesic potency was: E(56)>O(5)≥T(2.6)>M(1), and similar to this, the relative order of hyperthermic potency was: E(37)>O(3)≥T(2.3)>M(1). Morphine (phenanthrene-type) and fentanyl (4-anilinopiperidine-type) derivatives produced hyperthermia in rats at doses about 2 times lower, and 6–11 times higher, than their median antinociceptive doses, respectively. This study is first to identify difference between these two classes of opioid drugs in their potencies in producing hyperthermia. Further studies are needed to clarify the significance of these findings.     

Cancer Mortality Among Men in Central Serbia: 1985-2006 Survey Study

Aim

To analyze cancer mortality trends in men in Central Serbia during 1985-2006 period.

Methods

Mortality rates and trends for the most frequent cancers in men (lung, stomach, colorectal, pancreatic, and prostate cancer) were calculated. Mortality rates for all cancers were adjusted by direct standardization. Percentage changes of the rates were calculated as the percentage difference between the rates of two successive years and then as a mean of these changes for the entire observed period. Trend lines were estimated using linear regression.

Results

Total cancer mortality in men increased, with mean percentage of annual changes being 1.53% (95% confidence interval [CI], -0.09-3.16). Lung, stomach, colorectal, pancreatic, and prostate cancers represented 58.1% and 61.6% of total cancer deaths in 1985 and 2006, respectively. Increasing trends were observed for all investigated cancers: mean annual percentage change for lung cancer was 2.31%(95% CI, 1.03-3.59), for colorectal cancer 2.23% (95% CI, -0.18-4.65), for prostate cancer 3.06% (95% CI, -2.07-8.18), and for pancreatic cancer 1.58% (95% CI, -2.17-5.32). Stomach cancer mortality significantly decreased in age groups 40-49 and 50-59 years.

Conclusion

The most frequent cancers in men in Central Serbia, ie, lung, colorectal, prostate, and pancreatic cancer, showed an increasing trend. Only stomach cancer mortality decreased over time.Cancer mortality in the European Union (EU) (1) and the United States (2) peaked in the late 1980s and has declined thereafter. Since 1988, the total cancer mortality in men from the EU has leveled off, and declined by an average 1.3% per year over the last 10 years due to the combined effect of early detection and improved treatment (3). The prevention of cancer in the EU was defined by the Code Against Cancer in 1987. The Code was revised in 1994 (4) and again in 2003 (5) as new member states entered the Union.There are geographic differences in cancer burden between Western and Eastern Europe. According to estimates from 2002, cancer mortality in men was higher in Central-Eastern European countries than in North-Western countries (6). In Serbia, neither prevention activities nor mass screening tests were applied, with the sole exception of the government’s effort to implement tobacco control.The aim of this study was to analyze recent changes in cancer mortality trends for men in Serbia, a country with approximately 5.5 million population (excluding the two autonomous provinces), in the period 1985-2006.     

Trichinella spiralis: shaping the immune response

The co-evolution of a wide range of helminth parasites and vertebrates represented a constant pressure on the host's immune system and a selective force for shaping the immune response. Modulation of the immune system by parasites is accomplished partly by dendritic cells. When exposed to helminth parasites or their products, dendritic cells do not become classically mature and are potent inducers of Th2 and regulatory responses. Treating animals with helminths (eggs, larvae, extracts) causes dampening or in some cases prevention of allergic or autoimmune diseases. Trichinella spiralis (T. spiralis) possess a capacity to retune the immune cell repertoire, acting as a moderator of the host response not only to itself but also to third party antigens. In this review, we will focus on the ability of T. spiralis-stimulated dendritic cells to polarize the immune response toward Th2 and regulatory mode in vitro and in vivo and also on the capacity of this parasite to modulate autoimmune disease--such as experimental autoimmune encephalomyelitis.     

The association of V249I and T280M fractalkine receptor haplotypes with disease course of multiple sclerosis

We investigated the association of CX3CR1 genotypes/haplotypes with MS and performed the prediction analysis of protein sequence variants' effects on CX3CL1/CX3CR1 interaction. We found no association of CX3CR1 with MS susceptibility. Frequency of I(249)T(280) haplotype was significantly lower in SP compared to RR patients (RR>10 years, OR=0.30, 95%CI=0.11-0.79, p=0.01; OR=0.53, 95%CI=0.18-1.56, p=0.2, in SP<10 years vs. RR>10 years). Prediction analysis showed that I249 T280 protein variant would significantly affect CX3CL1/CX3CR1 interaction. Our results suggest that CX3CR1 I???T??? haplotype could have protective effect for switch to SP MS. Further research is warranted to validate and replicate currently observed results.     

Changes in the astrocytic aquaporin‐4 and inwardly rectifying potassium channel expression in the brain of the amyotrophic lateral sclerosis SOD1G93A rat model

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting upper and lower motor neurons. Dysfunction and death of motor neurons are closely related to the modified astrocytic environment. Astrocytic endfeet, lining the blood–brain barrier (BBB), are enriched in two proteins, aquaporin‐4 (AQP4) and inwardly rectifying potassium channel (Kir) 4.1. Both channels are important for the maintainance of a functional BBB astrocytic lining. In this study, expression levels of AQP4 and Kir4.1 were for the first time examined in the brainstem and cortex, along with the functional properties of Kir channels in cultured cortical astrocytes of the SOD1^G93A rat model of ALS. Western blot analysis showed increased expression of AQP4 and decreased expression of Kir4.1 in the brainstem and cortex of the ALS rat. In addition, higher immunoreactivity of AQP4 and reduced immunolabeling of Kir4.1 in facial and trigeminal nuclei as well as in the motor cortex were also observed. Particularly, the observed changes in the expression of both channels were retained in cultured astrocytes. Furthermore, whole‐cell patch‐clamp recordings from cultured ALS cortical astrocytes showed a significantly lower Kir current density. Importantly, the potassium uptake current in ALS astrocytes was significantly reduced at all extracellular potassium concentrations. Consequently, the Kir‐specific Cs⁺‐ and Ba²⁺‐sensitive currents were also decreased. The changes in the studied channels, notably at the upper CNS level, could underline the hampered ability of astrocytes to maintain water and potassium homeostasis, thus affecting the BBB, disturbing the neuronal microenvironment, and causing motoneuronal dysfunction and death. © 2012 Wiley Periodicals, Inc.     

Impact of stem cell source on allogeneic stem cell transplantation outcome in hematological malignancies

BACKGROUND/AIM: Peripheral blood (PB) is used more frequently as a source of stem cells (SCs) for allogeneic transplantation. However, the influence of cell source on the clinical outcome of SC transplantation is not yet well established. The aim of this study was to compare the results of PBSC transplantation (PBSCT) with bone marrow transplantation (BMT) on the basis of engraftment, frequency and severity of immediate (mucositis, acute Graft versus Host Disease--aGvHD) and delayed (chronic GvHD--cGvHD) complications, as well as transplant-related mortality (TRM), transfusion needs, relapses and overall survival (OS). METHODS: We analyzed 158 patients, women/men ratio 64/94 median age 29 (range 9-57), who underwent allogeneic SC transplantation between 1989 and 2009. All included patients had diseases as follows: acute myeloid leukemia (AML)--39, acute lymphoblastic leukemia (ALL) 47, chronic myeloid leukemia (CML)--32, myelodysplastic syndrome (MDS)--10, Hodgkin's lymphoma (HL)- 2, multiple myeloma (MM) 3, granulocytic sarcoma (GrSa) 3, severe aplastic anemia (sAA)--22. The patients underwent transplantations were divided into two groups: BMT group (74 patients) and PBSCT group (84 patients). Each recipient had HLA identical sibling donor. SCs from bone marrow were collected by multiple aspirations of iliac bone and from PB by one "Large Volume Leukapheresis" (after recombinant human granulocyte colony stimulating factor, rHuG-CSF) application (5-12 microg/kgbm, 5 days). Conditioning regimens were applied according to primary disease, GvHD prophylaxis consisted of combination of a cyclosporine A and methotrexate. Results. Engraftment, according to the count of polymorphonuclear and platelets, were significantly (p < 0.001) faster in the PBSCT vs BMT group. The needs for transfusion support were significantly (P < 0.01) higher in the BMT group. Those patients had more frequently oropharingeal mucositis grade 3/4 (33.3% vs 10.0%, p < 0.05). There were no significant differences in the incidence of aGvHD and cGvHD between the two groups. The patients who underwent PBSCT had more frequently extensive cGvHD in comparison with the BMT group (29.1% vs 11.29%, p < 0.05). SC source (SCS) had no significant influence on the TRM (21.62% vs 23.8%, p = 0.64) and the incidence of relapses (21.6% vs 29.7%, p = 0.32). Finally, the patients treated by BMT hd a significantly better OS (logrank 2.33, p < 0.05). Conclusion. SCs harvesting from PB resulted in improved cell yield, faster engraftment, as well as in a decrease of immediate transplantation related complications with a reduced treatment cost. Allogeneic PBSCT were associated with more frequent extensive cGvHD, while the influence of SCS in TRM and relapses was not observed. Finally, the long-term OS was better in the patients treated by BMT. To verify impact of SC source on transplantation (PBSCT vs BMT) overall efficacy, more larger randomized clinical studies are needed.