Modulating gut immunity and neoplasia with oral cytokine adjuvants.

Oral administration of particulate IL-10 suppressed polyposis, ameliorated systemic pathology and extended lifespan in APCmin/+ mice. Therapeutic effect was associated with selective activity of IL-10 on intestinal CD4+Foxp3+RORγt+IL-17+ pathogenic T-regulatory cells. Studies were recently extended to a bacterially-driven murine colon adenocarcinoma model with similar results. Clinical implications of these findings are discussed.

Effects of melatonin on the serum levels of pro-inflammatory cytokines and tissue injury after renal ischemia reperfusion in rats.

We investigated the changes in the serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6, the pro-inflammatory cytokines, and the possible effect of melatonin on the modulation of these inflammatory molecules after renal ischemia reperfusion (IR). The study was carried out in the laboratory of Department of Pharmacology. Forty-six male Wistar albino rats were divided into five groups as control (n=6), positive control (n=4), sham (n=12), renal IR (n=12), and renal IR melatonin (n=12). After 1 h renal pedicle occlusion, the blood samples were taken for the measurement of cytokine levels at second hour of the reperfusion. The rats were sacrificed after 24 h of reperfusion for histopathological evaluation. Melatonin or vehicle was administrated to IR rats. Lipopolysaccharide (LPS) was administered to the positive control group and the blood was taken at fourth hour. Serum TNF-α levels increased significantly in renal IR and LPS groups. Serum IL-6 levels were not different from control except the LPS group. There was no significant correlation between the serum TNF-α levels and the histopathological score after renal IR. Melatonin treatment reversed the increase of serum TNF-α levels and histopathological injury in renal tissue after renal IR. Melatonin may have a protective effect by reducing the serum level of TNF-α in renal IR.

Modulation of inflammation by mesenchymal stem cell transplantation in peritoneal dialysis in rats.

AIM: The purpose of this study was to determine the effect of mesenchymal stem cell (MSC) transplantation on the peritoneal morphology and inflammation markers in rat models of peritoneal dialysis (PD). MATERIALS AND METHODS: Wistar albino rats were divided into two groups: control (C) (n = 8) and experimental groups (n = 50). PD solution was given to the experimental group during 6 weeks. Then, experimental group was divided into three groups as PD, MSC, and placebo (P) groups. MSC group was treated with MSC (1.5 × 10(6) cells/kg) and P group was treated with phosphate buffer solution via intraperitoneal injection. Evaluation was performed to C and PD groups at the end of 6 weeks and to MSC and P groups at second and third week of the treatment (MSC-2, P-2, MSC-3, and P-3 groups). RESULTS: The submesothelial area was significantly thickened in PD and P groups compared to C and MSC groups. Peritoneal fibrosis was seen in P-3 group but not in MSC group. There were no significant differences between the MSC-3 and C groups according to morphological findings. Levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly increased in MSC-2 group compared to the other groups (p-values ranged from 0.0001 to 0.04). TNF-α and IL-6 levels in MSC-3 and P-3 groups were lower than PD and C groups (p < 0.0001 for TNF-α and p = 0.0001-0.002 for IL-6). CONCLUSION: Giving MSC may protect the peritoneal membrane from the deleterious effect of PD and extend the life of the peritoneal membrane. Our study is the first on this issue and more detailed studies are needed.

The effects on immune response of levamisole treatment following infection of U-937 macrophages with Candida albicans.

The aim of this study was to investigate the effects on the immune response of levamisole alone and in conjunction with Candida albicans stimulation in human macrophage cell culture by determining the alterations in the levels of cytokine release. Levamisole treatment was performed before, during and after infecting U-937 human macrophage cells with C. albicans. In cell supernatants, interleukin (IL)-1b, IL-12, IL-18, tumour necrosis factor alpha (TNF-α) levels were measured by ELISA. In vitro levamisole treatment accompanied by C. albicans stimulation significantly increased IL-12, IL-1ß and IL-18 production in macrophage cells (p < 0.05). It was observed that when administered before C. albicans infection, levamisole significantly increased IL-12 and IL-1ß production in macrophage cells (p < 0.05). Another finding was that when applied to macrophage cells simultaneously with C. albicans infection, or before infection with C. albicans, levamisole suppressed the TNF-ß production stimulating effect of C. albicans (p < 0.05). These results indicated that levamisole could be useful in treating patients infected with C. albicans or in protecting individuals under the risk of being infected with this pathogen. There is a need for further experimental and clinical studies on this hypothesis.

In vitro antimicrobial activity of propolis, BioPure MTAD, sodium hypochlorite, and chlorhexidine on Enterococcus faecalis and Candida albicans.

OBJECTIVE: To evaluate the antimicrobial effect by measuring the minimum inhibitory concentration MIC and minimum bactericidal concentration MBC of propolis, BioPure MTAD, 5% sodium hypochlorite (NaOCl), and 2% chlorhexidine CHX on Enterococcus faecalis (E. faecalis) and Candida albicans (C. albicans) in vitro. METHODS: This study was performed in the Faculty of Dentistry and Pharmacy at Erciyes University, Kayseri, Turkey from February to April 2010. Ethanol extract of propolis (EEP) was prepared from propolis collected from Kayseri, Turkey, and proper media for microorganisms were prepared using sterile broth medium to give final concentrations between 0.002-2.4 mg/ml for propolis, 0.000125-0.512 mg/ml for CHX, and 1:2-1:4096 dilutions for NaOCl and BioPure MTAD. Using the macrobroth dilution method, MIC, and MBC values of irrigants on the growth of E. faecalis and C. albicans were determined. RESULTS: Propolis and other irrigants were found to be effective on C. albicans and E. faecalis. Propolis and NaOCl were more effective in lower concentrations on C. albicans than on E. faecalis. In contrast, CHX and MTAD were more effective in lower concentrations on E. faecalis than on C. albicans. CONCLUSION: Propolis showed antimicrobial activity against E. faecalis and C. albicans. It appears that propolis is an effective intracanal irrigant in eradicating E. faecalis and C. albicans.

Classification of root canal microorganisms using electronic-nose and discriminant analysis.

BACKGROUND: Root canal treatment is a debridement process which disrupts and removes entire microorganisms from the root canal system. Identification of microorganisms may help clinicians decide on treatment alternatives such as using different irrigants, intracanal medicaments and antibiotics. However, the difficulty in cultivation and the complexity in isolation of predominant anaerobic microorganisms make clinicians resort to empirical medical treatments. For this reason, identification of microorganisms is not a routinely used procedure in root canal treatment. In this study, we aimed at classifying 7 different standard microorganism strains which are frequently seen in root canal infections, using odor data collected using an electronic nose instrument. METHOD: Our microorganism odor data set consisted of 5 repeated samples from 7 different classes at 4 concentration levels. For each concentration, 35 samples were classified using 3 different discriminant analysis methods. In order to determine an optimal setting for using electronic-nose in such an application, we have tried 3 different approaches in evaluating sensor responses. Moreover, we have used 3 different sensor baseline values in normalizing sensor responses. Since the number of sensors is relatively large compared to sample size, we have also investigated the influence of two different dimension reduction methods on classification performance. RESULTS: We have found that quadratic type discriminant analysis outperforms other varieties of this method. We have also observed that classification performance decreases as the concentration decreases. Among different baseline values used for pre-processing the sensor responses, the model where the minimum values of sensor readings in the sample were accepted as the baseline yields better classification performance. Corresponding to this optimal choice of baseline value, we have noted that among different sensor response model and feature reduction method combinations, the difference model with standard deviation based dimension reduction or normalized fractional difference model with principal component analysis based dimension reduction results in the best overall performance across different concentrations. CONCLUSION: Our results reveal that the electronic nose technology is a promising and convenient alternative for classifying microorganisms that cause root canal infections. With our comprehensive approach, we have also determined optimal settings to obtain higher classification performance using this technology and discriminant analysis.

Bacterial adhesion of porphyromonas gingivalis on provisional fixed prosthetic materials.

BACKGROUND: When provisional restorations are worn for long term period, the adhesion of bacteria becomes a primary factor in the development of periodontal diseases. The aims of this study were to evaluate the surface roughness and bacterial adhesion of four different provisional fixed prosthodon-tic materials. METHODS: Ten cylindrical specimens were prepared from bis-acrylic composites (PreVISION CB and Protemp 3 Garant), a light-polymerized composite (Revotek LC), and a polymethyl methacrylate-based (Dentalon) provisional fixed prosthodontic materials. Surface roughness was assessed by profilometry. The bacterial adhesion test was applied using Porphyromonas gingivalis (P. gingivalis) and spectro-fluorometric method. Statistical analysis was performed using ANOVA and Dunnett t-tests. RESULTS: All tested materials were significantly rougher than glass (P < 0.05). Revotek LC had the greatest fluorescence intensity, PreVISION and Protemp 3 Garant had moderate values and all of them had significantly more bacterial adhesion compared to glass (P < 0.05). Dentalon had the lowest fluorescence intensity among the provisional fixed prosthodontic materials. CONCLUSION: The quantity of bacterial adhesion and surface roughness differed among the assessed provisional fixed prosthodontic materials. The light-polymerized provisional material Revotek LC had rougher surface and more bacterial adhesion compared with the others.

The influence of omentectomy on bacterial clearance: an experimental study.

BACKGROUND: The influence of an omentectomy on peritoneal defense mechanisms and its clinical consequences have not been fully elucidated. In the present study, we aimed to investigate the influence of omentectomy on bacterial growth in blood and tissue specimen cultures in rats with experimental peritonitis. METHODS: Fifty Wistar-Albino rats were included in the present study. Animals were assigned into five groups as follow: Group 1 (n = 10), omentectomy alone; Group 2 (n = 10), omentectomy + bacterial peritonitis; Group 3 (n = 10), bacterial peritonitis alone; Group 4 (n = 10), laparotomy alone; and Group 5 (n = 10), sham group. Culture positivity rate and bacterial growth (colony forming units [CFU]/gram tissue) were assessed in mesenteric lymphoid tissue and venous blood of all animals. RESULTS: Bacterial growth in lymphoid tissue was significantly higher in Groups 2 and 3 than others (both, p < 0.05). CFU of Escherichia coli in lymphoid tissue was significantly higher in Group 2 than in Groups 1 and 3 (both, p < 0.05/4). Blood culture positivity was significantly higher in Group 2 than the others (both, p < 0.05). CONCLUSION: The omentum has an important role in the host peritoneal defense system. Peritoneal infection may pursue a more severe course with increased bacterial entrance into the blood in the absence of the omentum.

[Cystic echinococcosis in Turkey from 2001-2005]. / Türkiye'de 2001-2005 Yillari Arasinda Kistik Ekinokokkozis.

Cystic echinococcosis (CE) caused by the metacestode form of Echinococcus granulosus is a major public health problem especially in animal-raising regions of the world. In the present study, CE cases were determined during 2001-2005 by investigating different hospital and health directorship documents and Health Ministry documents, retrospectively. Our results show that there were 2534 (13.13%) cases in the Marmara region; 2114 (16.94%), in the Aegean region; 2578 (16.09%), Mediterranean region; 5404 (38.57%), in the Middle Anatolian region; 428 (5.70%), in the Black Sea region; 844 (6.80%), in the eastern Anatolian region; and 887 (2.75%), in the southeastern Anatolian region making a total of 14,789 CE cases. Finally, it has been determined that the patients were hospitalized for a total of 149,464 days.

Effect of melatonin on testicular ischemia/reperfusion injury in rats: is this effect related to the proinflammatory cytokines?

OBJECTIVE: To determine whether the protective effect of melatonin in testicular ischemia/reperfusion (IR) injury is mediated by the proinflammatory molecules. DESIGN: Experimental study. SETTING: University pharmacology laboratory. ANIMAL(S): Fifty-six 8-week-old male Wistar albino rats. INTERVENTION(S): Left testicular artery and vein was occluded for 1 hour, followed by 3 hours or 24 hours of reperfusion. Melatonin (10 mg/kg IP) or vehicle (1% ethanol in saline) was given 10 minutes before ischemia. MAIN OUTCOME MEASURE(S): Malondialdehyde (MDA), protein carbonyl (PC) content, myeloperoxidase (MPO) activity, and proinflammatory cytokines TNF-alpha, IL-1beta, and IL-6 were examined in testicular tissue after 3 hours of reperfusion. Histologic examination was made after 24 hours of reperfusion. RESULT(S): The MDA, PC, and MPO levels in testicular tissue increased significantly after IR, but the proinflammatory cytokine levels did not change. Melatonin treatment decreased lipid and protein oxidation and ameloriated histopathologic alterations induced by IR without any change in proinflammatory cytokine levels. CONCLUSION(S): The protective effect of melatonin on IR-induced testiculary injury is related to its antioxidant properties but not to proinflammatory cytokines.

Melatonin protects from ischemia/reperfusion-induced renal injury in rats: this effect is not mediated by proinflammatory cytokines.

The pathophysiologic mechanisms leading to acute ischemic renal failure are not completely understood. Melatonin, a compound with well-known antioxidant properties, reduces IR-induced renal injury. The purpose of the present study was to investigate the changes in levels of tumor necrosis factor (TNF)-alpha, IL-beta, and IL-6 in postischemic reperfused renal tissue, and to determine whether the protective effect of melatonin is related the modulation of the production of these inflammatory molecules. Male Wistar albino rats were unilaterally nephrectomized and subjected to 1 hr of renal pedicle occlusion followed by 2 hr or 24 hr of reperfusion. Melatonin (10 mg/kg, i.p.) or vehicle was administrated at 10 min prior to ischemia. After 24 hr of the reperfusion, following decapitation, kidney samples were taken both for histologic examination and for the determination of malondialdehyde (MDA), myeloperoxidase (MPO) activity, total antioxidant capacity (TAC), total oxidative stress (TOS), creatinine, and blood urea nitrogen (BUN). These were measured in serum samples. TNF-alpha, IL-beta, and IL-6 were measured in kidney samples after 2 hr of reperfusion. IR caused a significant increase in renal MDA, MPO, TOS, creatinine, and BUN while decrease TAC without any change in TNF-alpha, IL-beta, and IL-6 levels. Melatonin treatment reduced the biochemical indices without any change in the cytokine levels and ameliorated histopathologic alterations induced by IR. The protective effect of melatonin on IR-induced renal injury is related to its antioxidant properties but not to proinflammatory cytokines.

[Parasitic fauna and the frequency of Entamoeba histolytica/Entamoeba dispar detected by ELISA in stool samples in Sanliurfa, Turkey]. / Sanliurfa'da parazit faunasi ve ELISA yöntemi ile diskida Entamoeba histolytica/Entamoeba dispar sikligi.

Amoebiasis is a significant health problem in developing countries. Humans are infected by two morphologically identical species of Entamoeba. Entamoeba histolytica causes amebic colitis and liver abscess, and Entamoeba dispar is noninvasive. The aim of this study was to determine the prevalence of the E. histolytica/E. dispar complex using the ELISA method on stools of patients. A total of 1600 stool specimens were examined using Lugol preparations and the modified Ritchie method. A total of 583 (36.4%) of the stool specimens were found to be positive for one or more than one parasite. Twenty two subjects (3.8%) of the study population with intestinal parasites harbored two parasites and one subject (0.2%), three parasites. A total of 87 stool specimens that were doubtful using the Lugol method were examined by the E. histolytica specific sensu-lato antigen based ELISA test and the trichrome staining method. Of these 87 specimens, 23 (26.4%) specimens were positive for E. histolytica/E. dispar trophozoites/cysts microscopically using trichrome staining and 19 (21.7%) of the stool specimens were found to be positive for the E. histolytica/E. dispar complex by the ELISA test.

IgG and IgG subclass antibodies in patients with active cutaneous leishmaniasis.

This research was planned to detect IgG and IgG subclasses in sera of patients with active cutaneous leishmaniasis (CL). Sera from 30 patients with active CL aged between 10 and 50 years and from 30 healthy controls aged between 8 and 50 years were included in the study. Levels of IgG and its subclasses were measured by a nephelometer. Levels of IgG, IgG1 and IgG3 in the CL patients were higher than in the controls. In addition, IgG and IgG1, and IgG and IgG3 levels showed a significant positive correlation. These results showed that IgG subclasses could possibly be used as a helpful diagnostic marker in CL.

Serum malondialdehyde level in children infected with Vampirolepis nana.

BACKGROUND: Vampirolepis nana is the only human tapeworm in which the intermediate host is not necessary and transmission is from person to person. In this study the changes of serum malondialdehyde level, that is, the oxidative stress hypothesis in patients infected with V. nana, was investigated. METHODS: Serum malondialdehyde concentration activity was measured in 32 patients who were positive for intestinal parasite of V. nana. Levels were obtained for the positively infected patients and their age and gender were matched to 32 healthy controls. RESULTS: The difference between malondialdehyde levels of patients infected with V. nana and the control group was statistically significant both for females (P < 0.05) and males (P < 0.05). In the patient and control groups, no correlation was found between age and malondialdehyde levels both in females and males. In addition, no significant correlation could be found between malondialdehyde levels of both females and males for the patient and control groups. CONCLUSION: Malondialdehyde levels were clearly increased in the patients infected with V. nana.

Effectiveness of topical taurolidine versus ciprofloxacin, ofloxacin, and fortified cefazolin in a rabbit Staphylococcus aureus keratitis model.

PURPOSE: Taurolidine is a broad-spectrum, non antibiotic antimicrobial agent, not previously tested against the common causes of bacterial keratitis. This study, employing an experimental rabbit model of Staphylococcus aureus keratitis, investigated the effectiveness of topical taurolidine in reducing the number of bacteria, and its effectiveness was compared with topical ciprofloxacin, ofloxacin, and 5% cefazolin. METHODS: The right corneas of all rabbits were intrastromally injected with 100 colony-forming units of Staphylococcus aureus ATCC strain 25923. The animals were divided into the following seven groups: Group 1 (6 rabbits) received taurolidine, group 2 (6 rabbits) received ciprofloxacin, group 3 (6 rabbits) received ofloxacin, group 4 (6 rabbits)received cefazolin, group 5 (5 rabbits) received polyvinylpyrrolidone (vehicle),group 6 (4 rabbits) received sterile water, and group 7 (4 rabbits) was left un-treated (control group). The eyes were topically treated every 30 min with the above-mentioned substances from 4 to 9 h postinjection. One hour after the last drop administration (at 10 h postinjection), signs of inflammation were scored in a masked fashion by slit-lamp examination. Then, their corneas were processed. The number of colony-forming units (cfu) per cornea in all eyes was also determined. RESULTS: All antimicrobial (taurolidine, ciprofloxacin, ofloxacin, and cefazolin) treatments significantly reduced cfu numbers and slit-lamp examination scores compared with untreated eyes, eyes that received the vehicle, or eyes with sterile water (all p values <0.05). Regarding cfu numbers, although taurolidine therapy was significantly less effective than ciprofloxacin or ofloxacin,there was no significant difference between taurolidine and cefazolin groups.However, taurolidine had similar clinical examination scores with the other antimicrobials, while it had lower scores than the vehicle, sterile water, or un-treated eyes. CONCLUSIONS: The results obtained in this study suggest that topicaltaurolidine is an effective, novel ocular chemotherapeutic agent for the therapy of rabbit experimental Staphylococcus aureus keratitis. This drug may be a useful and promising ocular antimicrobial.

Evaluation of oxidative stress in cutaneous leishmaniasis.

Oxidative stress occurs when there is excessive free-radical production or a low antioxidant level. The role of free radicals in the pathogenesis and in the progression of many diseases has often been discussed, but it has not been widely investigated in leishmaniasis. However, measurement of oxidants and antioxidants in the serum seems to be of great value. In this study, we aimed to determine lipid peroxidation levels as markers of oxidative stress in the serum of patients suffering from cutaneous leishmaniasis, which is a common health problem in our region of Southern Anatolia, Turkey. Forty patients aged between 5-50 years and forty controls aged between 5-50 years were included in the study. The LPO levels of the patients with active cutaneous leishmaniasis were significantly higher (p<0.001) than those of healthy controls. As a result, it is possible to conclude that patients with cutaneous leishmaniasis are affected by oxidative stress, which may contribute to the progression of the disease.

A preliminary approach to the separation of Leishmania cell-surface antigens.

The purpose of the current study was to characterize Leishmania cell-surface antigens by two different methods established for the purification of glycoproteins and proteins, and to point out a useful approach to define their size and mass heterogeneity. L. tropica parasites were initially isolated from patients with active cutaneous leishmaniasis and were then cultured in vitro. The parasite-cell layer was solubilised with 6 M guanidinium chloride (GuHCl) and subsequently prepared for the purification procedure. The methods used in this work were gel filtration chromatography and isopycnic density-gradient centrifugation. Because of the presence of a substantial amount of non-specific proteins in the culture medium, these methods were not effective alone in distinguishing these antigens. However, a good idea of their N-glycosylated structures could be obtained by using Periodic acid-Schiffs (PAS) and Con A lectin, and also size and mass heterogeneity. A combination of these methods effected a clear separation of the antigens. Amino acid analysis of the purified antigens was performed to positively identify them as well-known Leishmania cell-surface antigen gene products. The results confirmed the presence of more than one cell-surface antigen on the Leishmania parasite and the combination of gel chromatography and density-gradient centrifugation could be useful for their isolation.

Alterations of oxidative-antioxidative status in human cutaneous leishmaniasis.

Enhanced lipid peroxidation and decreased antioxidant defences have been defined in several diseases. In the present study, we aimed to evaluate the oxidative-antioxidative status of patients with cutaneous leishmaniasis (CL). Concentrations of erythrocyte lipid peroxidation (LPO), as an indicator for the oxidative status, reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and serum vitamin C levels, as indicators for the antioxidative status, were measured. Seventy patients aged between 15 and 50 years (38 patients had active CL and 32 patients had healed CL) and 40 healthy controls aged between 19 and 50 years were included in the study. LPO and GSH of the patients with active CL were significantly higher (p < 0.001), whereas erythrocyte GSH-Px and serum vitamin C levels were lower (p < 0.001, p < 0.01 respectively) than those of healthy controls. There was a significant inverse correlation between LPO and serum vitamin C level (r=-0.32, p < 0.05) in active CL. No significant correlation of LPO, GSH, GSH-Px and serum vitamin C levels in control groups or in the group with healed CL was detected. In the light of our findings it is possible to conclude that patients having CL are affected by oxidative stress, which most likely induces the endogenous antioxidant system. An imbalance between the oxidant and antioxidant systems occurs and the suppressed antioxidants and increased lipid peroxidation may contribute to the progression of the disease.

The experimental model of hydatidosis in rabbit testis. A preliminary study.

OBJECTIVES: Although no part of the human anatomy is invulnerable to hydatid disease, it has been reported to occur mostly in vital organs such as liver, lungs and brain. Hydatid disease of the urinary tract is uncommon accounting for only 2% of all such cases. Testes are extremely rare sites for echinococcosis. To our knowledge there are only 3 cases of testicular hydatid cyst described. In this animal model, we studied echinococcosis in rabbit testis. METHODS: We directly infected the unilateral testis of 4 male rabbits with infective protoscolices via intratesticular injection and housed them under pathogen-free conditions for 10 weeks. All rabbits survived during the follow-up period and then, at the 10th week, all testes were removed for histopathologic investigation. RESULTS: Despite of the direct infection of the rabbit testes with Echinococcus granulosus, there was no demonstrable hydatid cyst after a 10-week period except from some fibrosis in the injection tract of the testicular tissue in 1 case. CONCLUSION: The testes are extremely rare anatomic locations for echinococcosis infection. The mechanism of this resistance should be another reason apart from blood-testicular barrier. We think that low temperature in the scrotum or different properties of the testicular tissue may be the reasons of this defense mechanism. If this hypothesis clarifies with the further studies, new treatment options may be defined in the medical literature for the hydatid cyst.