In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens

Cytotoxic T lymphocytes (CTL) respond to antigenic peptides presented on MHC class I molecules. On most cells, these peptides are exclusively of endogenous, cytosolic origin. Bone marrow-derived antigen-presenting cells, however, harbor a unique pathway for MHC I presentation of exogenous antigens. This mechanism permits cross-presentation of pathogen-infected cells and the priming of CTL responses against intracellular microbial infections. Here, we report a novel diphtheria toxin-based system that allows the inducible, short-term ablation of dendritic cells (DC) in vivo. We show that in vivo DC are required to cross-prime CTL precursors. Our results thus define a unique in vivo role of DC, i.e., the sensitization of the immune system for cell-associated antigens. DC-depleted mice fail to mount CTL responses to infection with the intracellular bacterium Listeria monocytogenes and the rodent malaria parasite Plasmodium yoelii.     

Use of chemotherapy at the end of life in Turkey

Background

An increasing number of patients receive palliative chemotherapy near the end of life. The aim of this study is to evaluate the aggressiveness of chemotherapy in Turkish individuals near the end of life.

Methods

Patients diagnosed with solid tumors and died from 2010 to 2011 in the medical oncology department of Akdeniz University were included in the study. Data about the diagnosis, treatment details and imaging procedures were collected.

Results

Three hundred and seventy-three people with stage IV solid tumors died from 2010 to 2011 in our clinic. Eighty-nine patients (23.9%) patients underwent chemotherapy in the last month of life while 39 patients (10.5%) received chemotherapy in the last 14 days. The probability of undergoing chemotherapy in the last month of life was influenced by: age, ‘newly diagnosed’ patients, and performance status. There was no significant association of chemotherapy in the last month of life with gender and tumor type. Having a PET-CT scan did not alter the chemotherapy decision.

Conclusion

In conclusion, chemotherapy used in the last month of life in a tertiary care center of Turkey is high. Increasing quality of life should be a priority near the end of life and physicians should consider ceasing chemotherapy and direct the patient to early palliative care.

     

Protective effects of melatonin against spinal cord injury induced oxidative damage in rat kidney: A morphological and biochemical study

Spinal cord injury (SCI) induced oxidative stress affects multiple organ systems including the kidney. We studied the possible protective effects of melatonin on SCI-induced oxidative damage in renal tissues of rats. Wistar albino rats (n = 24) were exposed to SCI and divided into vehicle- or melatonin-treated SCI groups. Melatonin was administred intraperitoneally at a dose of 10 mg/kg for seven days. Renal tissues were investigated by light and electron microscopy. Furthermore, tissue malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) and superoxide dismutase (SOD) activities were also determined. In the vehicle-treated SCI group, the renal histology was disturbed compared to controls, whereas the melatonin-treated SCI group showed significantly reduced degeneration of renal tissue as seen by both light and electron microscopy. MDA levels, MPO and SOD activities were increased and GSH levels were decreased in the vehicle-treated SCI group compared to controls. On the other hand, decreased MDA levels and MPO activities and increased GSH levels were observed in the melatonin-treated SCI group compared to vehicle-treated SCI group. These results showed that experimentally induced SCI caused oxidative stress in the rat kidney, whereas melatonin treatment reduced oxidative stress, suggesting that it may be used as a complementary therapy of renal problems occurring following SCI.     

Is human kallikrein-11 in gastric cancer treated with surgery and adjuvant chemoradiotherapy associated with survival?

Human kallikreins (hKs) have been reported to be involved in human cancers, and several hKs are promising biomarkers of various cancers, such as prostate, ovarian, breast, and testicular cancer. In the present study, we aimed to evaluate the prognostic value of immunohistochemical expression of hK11 in patients with gastric cancer. The study included 55 (36 men and 19 women; 58 ± 10 years of mean age) patients with gastric cancer treated with surgery and adjuvant chemoradiotherapy. Tissue sections were evaluated immunohistochemically with a monoclonal anti-hK11 antibody. Of the 55 patients, 35 (63.6%) were hK11-positive and 20 (36.4%) were hK11-negative. Disease-free and overall survival rates were significantly higher in patients with hK11 positive than in those with hK-11 negative expression (24 months vs. 11 months, p: 0.043; 29 months vs. 13 months, p: 0.038, respectively). In conclusion, hK11 expression in gastric cancer appears to be associated with a better prognosis. hK11 may be a prognostic biomarker of gastric cancer. On the other hand, it is needed to elucidate the mechanisms underlying the regulation of hK11 expression in gastric cancer.     

Interleukin‐2 gene polymorphism in Turkish patients with Behçet's disease and its association with ocular involvement

Behçet's disease (BD) is a chronic immune‐mediated systemic disease, characterized by oral and genital lesions and ocular inflammation. Several cytokine genes may play crucial roles in host susceptibility to BD, because the cytokine production capacity varies among individuals and depends on the cytokine gene polymorphisms. The association of the interleukin (IL)‐2 gene polymorphisms with the susceptibility to BD was investigated in this study. DNA samples were obtained from a Turkish population of 97 patients with BD and 76 healthy control subjects. Polymorphisms of IL‐2 gene at position ?330 and +166 were determined using the polymerase chain reaction with sequence‐specific primers. In the patients with BD, there was a significantly increased frequency of IL‐2 ?330 GT genotype. Interestingly, we demonstrated that the frequencies of IL‐2 ?330 GT and IL‐2 + 166 GG genotypes were increased in BD patients with ocular involvement, whilst IL‐2 ?330 TT genotype was significantly decreased. Also, analysis of allele frequency demonstrated that the presence of G allele at position +166 of IL‐2 seems to be a risk factor for ocular involvement. These results reveal that IL‐2 ?330 GT genotype may be a susceptibility factor for BD, whereas IL‐2 ?330 TT genotype seems to display a protective association with BD. Additionally, IL‐2 gene polymorphisms might be associated with ocular involvement in BD.     

Protective effect of lycopene against ochratoxin A induced renal oxidative stress and apoptosis in rats

This study was designed to investigate the possible protective effect of lycopene against the renal toxic effects of OTA. Male Sprague-Dawley rats (<200 g, n = 6) were treated with OTA (0.5 mg/kg/day) and/or lycopene (5 mg/kg/day) by gavage for 14 days. Histopathological examinations were performed and apoptotic cell death in both cortex and medulla was evaluated by TUNEL assay. Besides, biochemical parameters and activities of renal antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD); concentrations of total glutathione (GSH), and malondialdehyde (MDA) levels were measured. OTA treatment was found to induce oxidative stress in rat kidney, as evidenced by marked decreases in CAT (35%) activity and GSH levels (44%) as well as increase in SOD activity (22%) vs control group. Furthermore, TUNEL analysis revealed a significant increase in the number of TUNEL-positive cells in cortex (49%) and medulla (75%) in OTA administrated group compared to control (p < 0.05). Lycopene supplementation with OTA increased GPx1 activity and GSH levels, and decreased apoptotic cell death in both cortex and medulla vs. control. The results of this study showed that at least one of the mechanisms underlying the renal toxicity of OTA is oxidative stress and apoptosis is the major form of cell death caused by OTA. Besides, our data indicate that the natural antioxidant lycopene might be partially protective against OTA-induced nephrotoxicity and oxidative stress in rat.     

Is SHORT syndrome another phenotypic variation of PITX2?

Even though responsible genetic loci and mode of inheritance for the Rieger syndrome have been well established, the mode of inheritance and the genetic basis for SHORT syndrome are still uncertain. The purpose of this paper is to document a familial translocation of t(1;4)(q31.2;q25), in a mother and her son manifesting Rieger syndrome with polycystic ovaries and SHORT syndrome, respectively. It is suggested that these two syndromes may be different expressions of the same gene, PITX2, localized at 4q25. Our patient is the second with the association of Rieger syndrome and polycystic ovaries, and thus this may not be coincidental, moreover insulin resistance-related phenotypes, such as lipodystrophy and polycystic ovaries, can be major component of syndromes with Rieger eye malformation.