Evaluation of intestinal necrosis with laser Doppler in experimental mesenteric ischemia model.

BACKGROUND: Acute mesenteric ischemia (AMI) is responsible for one in a thousand emergency hospital admissions in America and Europe and is associated with high morbidity and mortality rates. Current diagnostic and treatment methods fall short of desired outcomes, often resulting in delayed diagnoses and difficulties in detecting ischemic bowel tissue during treatment. This study evaluates the diagnostic value of commonly used biochemical markers in clinical practice-creatine kinase, C-reactive protein (CRP), and lactate dehydrogenase (LDH)-alongside blood flow measurements using laser Doppler in a rat model of experimental mesenteric ischemia. We also compare these markers with pathological ischemia scoring. METHODS: Rats were divided into five groups: control, 1 hour, 2 hours, 3 hours, and 4 hours. Mesenteric ischemia was induced for the respective durations in each group. After these periods, we measured blood flow using laser Doppler. We also collected blood samples and intestinal biopsies for biochemical parameter analysis. These values were assessed in relation to intestinal viability using the Chiu ischemia scoring system. RESULTS: Blood flow measurement with laser Doppler correlated with both the duration and severity of bowel ischemia. No significant relationship was found between CRP levels and the duration of ischemia. However, creatine kinase and lactate dehydrogenase (LDH) levels were significantly higher in ischemia lasting into the third and fourth hours. CONCLUSION: Creatine kinase and lactate dehydrogenase (LDH) levels may be useful biomarkers in patients with suspected acute mesenteric ischemia (AMI). Blood flow measurements using laser Doppler can accurately identify intestinal loops for resection during surgery.

Local myelin damage in the hippocampus fluctuates gut microbiome profile and memory.

The concept of the gut-brain axis has focused research on how gut dysbiosis affects myelin biology in the brain. However, this axis has not been tested to determine whether it conveys the effects of myelin damage on the gut microbiome profile. Therefore, we aimed to investigate how myelin biology is correlated with gut microbiome profile. The impact of local myelin damage in the hippocampus on gut microbiome profile was investigated with 16S rRNA metagenomic sequence and molecular analysis of myelin biology-associated proteins, and its reflections on memory performance were tested with behavioral tests. Local myelin damage in the hippocampus triggered severe gut dysbiosis, p < .05, changed memory performance, p < .05, and deviated emotional responses. Moreover, myelin treatment with clemastine improved gut dysbiosis and behavioral deviations. Our study provides animal-based evidence on the direct interaction between glial biology in the hippocampus and gut microbiome profile. This study proposes a framework for generating new hypotheses bridging different systems to the gut-brain axis.

Improvement of cognitive deficit of curcumin on scopolamine-induced Alzheimer's disease models.

BACKGROUND: It has been suggested that curcumin may be useful in diseases with cognitive dysfunction because it slows the progression and leads to the improvement of cognitive functions. In this study, the protective effects of curcumin on scopolamine-induced rat models of cognitive impairment were evaluated. METHODS: 21 male Wistar Albino rats, 1 year old, 200±25 grams, were included in the study. They were divided into three groups (n: 7 in each group); the untreated control group, scopolamine group, and the group treated with curcumin and then exposed to scopolamine. Animals were evaluated for behavioral tasks with the Morris Water Maze test. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), total oxidative status (TOS), and total antioxidative status (TAS) were measured in hippocampal tissues. CRP levels were measured in serum specimens. RESULTS: We found that the length to reach the platform was the highest in the scopolamine group, and the lowest in the curcumin group (p<0.001). Time to reach the platform was the longest in the scopolamine group, and the shortest in the curcumin group (P=0.002). The length to reach the platform was the highest in the scopolamine group, and the lowest in the control group in the probe test (p<0.001). IL-6 levels were higher in the scopolamine group than the curcumin group (P=0.017) and the control group (P=0.005). CONCLUSION: We revealed that curcumin provides a protective effect on scopolamine-induced cognitive impairment mimicking Alzheimer's disease. The use of curcumin for the protection of cognition in individuals at risk of developing AD may be considered.

Effects of regular physical exercise on skin blood flow and cardiovascular risk factors in overweight and obese subjects / Efeitos do exercício físico regular sobre o fluxo sanguíneo da pele e nos fatores de risco cardiovascular em indivíduos com sobrepeso e obesidade

Objective: it is well known that low omentin levels and reduced bioavailability of nitric oxide (NO) are outgrowth of obesity. Besides, in obese subjects, microvascular dysfunction can be an initial stage of cardiovascular diseases. This situation can be evaluated with skin laser­Doppler flowmetry (LDF). Methods: in this study we investigated the effects of 12 weeks moderate physical exercise on microvascular reactivity and plasma levels of omentin and NO in 25 overweight and obese subjects. Control group was composed of 28 sedentary participants who were neither obese nor overweight. Microvascular reactivity was handled by measurement of skin blood flow from the ring finger of the right hand with LDF, which is a non­invasive method for evaluation. With this method, it was aimed to examine the post­occlusive reactive hyperemia response of the patients. None of the participants in both groups have never followed a regular exercise schedule in their life span. Results: with regular exercise, there was a statistically significant decrease in glucose (p=0.008), cholesterol (p=0.05), and triglyceride (p=0.048) levels, while body mass index, high­density lipoprotein, and low­density lipoprotein levels did not change significantly in overweight/obese group. Also, the omentin level significantly increased (p=0.01), but NO level did not change significantly. Moreover, the amount of change in omentin and NO levels measured before and after the physical exercise were significantly correlated (r=0.57). Considering the microcirculation, rest flow (p=0.001) and peak flow value of LDF (p=0.001) increased after the physical exercise. Conclusion: our study shows that moderate physical exercise affects microvascular reactivity and plasma levels of omentin in overweight and obese subjects.

Objetivo: sabe-se que níveis baixos de omentina e a reduzida biodisponibilidade de óxido nítrico (NO) são consequências da obesidade. Além disso, a disfunção microvascular pode ser um estágio inicial de doenças cardiovasculares em indivíduos obesos. Essa situação pode ser avaliada com a fluxometria de pele laser-Doppler (LDF). Métodos: foram investigados os efeitos do exercício físico moderado por 12 semanas na reatividade microvascular e nos níveis plasmáticos de omentina e NO em 25 indivíduos com sobrepeso e obesidade. O grupo controle foi composto por 28 participantes sedentários que não eram obesos nem com sobrepeso. A reatividade microvascular foi obtida pela medida do fluxo sanguíneo da pele do dedo anelar da mão direita com LDF, que é um método não invasivo de avaliação. Com este método, objetivou-se examinar a resposta da hiperemia reativa pós-oclusiva dos pacientes. Os participantes de ambos os grupos nunca seguiram um cronograma regular de exercícios em sua vida. Resultados: com o exercício regular houve diminuição estatisticamente significativa dos níveis de glicose (p=0,008), de colesterol (p=0,05) e de triglicerídeos (p=0,048), enquanto o índice de massa corporal e os níveis de lipoproteínas de alta e baixa densidade não se alteraram significativamente no grupo com sobrepeso/obesidade. Além disso, o nível de omentina aumentou significativamente (p=0,01), mas o nível de NO não apresentou modificações significas. Observou-se, também, que as modificações nos níveis de omentina e NO mensurados antes e após o exercício físico foram significativamente correlacionados (r=0,57). Em relação à microcirculação, os valores do fluxo de repouso (p=0,001) e do valor de fluxo de pico e da LDF (p=0,001) aumentaram após o exercício físico. Conclusão: nosso estudo mostra que o exercício físico moderado afeta a reatividade microvascular e os níveis plasmáticos de omentina em indivíduos com sobrepeso e obesidade.

The effect of tramadol on oxidative stress total antioxidant levels in rats with renal ischemia-reperfusion injury.

OBJECTIVE: To evaluate the protective effect of tramadol on renal tissue in rats with induced renal ischemia-reperfusion injury (I/R injury), and its effects on oxidative stress. MATERIAL AND METHODS: Thirty adult, male Wistar rats weighing 250-300 g were selected as subjects. Rats were randomized into 3 groups: group 1, sham; group 2, renal I/R injury; and group 3, renal I/R+Tramadol. In order to obtain ischemia in groups 2 and 3, renal artery was clamped for 1 h. Total oxidant status (TOS) and total antioxidant capacity (TAC) were analyzed using biochemical assays in the serum samples. RESULTS: TOS values were measured as 1.68±0.4 in group 1, 3.35±1.0 in group 2, and 3.49±0.9 in group 3. When group 1 was compared with group 2 and group 3, the TOS values of group 1 were significantly lower (p<0.05), whereas there was no difference between group 2 and group 3 (p>0.05). TAC values were measured as 1.65±1.4 in group 1, 1.85±0.1 in group 2, and 2.79±0.6 in group 3. The antioxidant status of group 1 was not significantly different from that of group 2 (p>0.05), whereas there was a significant difference between group 1 and group 3 (p>0.05). CONCLUSIONS: Tramadol has positive effects on antioxidant levels in renal I/R injury. We think that tramadol may be used in patients who underwent renal surgery and have I/R injury risk. There is a need for studies on this subject including human series.

Nigella sativa oil and thymoquinone reduce oxidative stress in the brain tissue of rats exposed to total head irradiation.

Purpose: To evaluate the antioxidant and radio-protective effects of Nigella sativa oil (NSO) and thymoquinone (TQ) on radiation-induced oxidative stress in brain tissue.Materials and methods: Fifty-four Sprague-Dawley rats were divided into six groups to test the radio-protective effectiveness of Nigella sativa oil and thymoquine administered by either orogastric tube or intraperitoneal injection. Appropriate control groups were also studied.Results: Brain antioxidant capacity, as measured by the levels of total superoxide scavenger activity (TSSA), non-enzymatic superoxide scavenger activity (NSSA), superoxide dismutase, paraoxonase (PON) activities, total antioxidant status and total sulfhydryl (-SH) group, were lower in the irradiation (IR) only group while xanthine oxidase (XO) activity, total oxidant status (TOS), oxidative stress index (OSI) and lipid hydroperoxide (LOOH) levels were higher in the group compared with all other groups. Brain glutathione-S-transferase (GST) activity significantly decreased in the IR only group when compared with the control groups. Glutathione peroxidase (GSH-Px) activity was lower in the IR only, NSO plus IR, TQ plus IR groups when compared with the control group of TQ. Arylesterase (ARYL) activity was not statistically significant in the IR only group compared with all other groups.Conclusions: The results suggest that Nigella sativa oil (NSO) and its active component, TQ, clearly protect brain tissue from radiation-induced oxidative stress.

Studying the effect of large neutral amino acid supplements on oxidative stress in phenylketonuric patients.

Background Oxidative stress may be one of the causes responsible for mental retardation in phenylketonuria (PKU) patients. Phenylalanine (Phe) reduces antioxidant defense and promotes oxidative stress by causing increase in reactive oxygen-nitrogen species. Our study aimed to investigate the effect of different treatments (amino acid mixture/large neutral amino acid [LNAA] supplements) on oxidative stress which are applied to late-diagnosed patients. To the best of our knowledge, this is the first study to investigate the effect of LNAA supplements on oxidative stress. Methods Twenty late-diagnosed classic PKU patients were included in this study. Patients were classified into two groups: patients under Phe-restricted diet and using Phe-free amino acid mixtures (Group I) (mean age: 13.8 ± 2.8), and patients taking LNAA supplements (Group II) (mean age: 14.8 ± 3.8). Healthy controls (mean age: 13.6 ± 4.8) with ages consistent with the ages of the patients in the experimental groups were included. Results Glutathione peroxidase is lower in patients of taking LNAA supplements than the control group (p = 0.022). Coenzyme Q10 is lower in patients of using Phe-free amino acid mixtures than the control group and it is significantly higher in Group II than Group I (p = 0.0001, p = 0.028, respectively). No significant differences were detected in total antioxidant status, total oxidant status, oxidative stress index, paraoxonase 1 and L-carnitine levels. Conclusions Different treatments affect oxidative stress parameters in PKU patients. In this study, although patients were followed up with classic PKU, patient-specific adjuvant antioxidant therapies should be implemented in response to oxidative stress.

Colostrum immunoglobulins and oxidative capacity may be affected by infant sex and maternal age and parity

Background/aim: The aims of this study were to determine the levels of the total antioxidant status (TAS), the total oxidant status (TOS), the oxidative stress index (OSI), and the concentration of immunoglobulin A (IgA) and M (IgM) in colostrum, and evaluate relationships between these parameters and maternal age, maternal parity, and infant sex. Materials and methods: The analysis was performed in serum samples of colostrum which were collected from 90 mothers on the first day of lactation between 10:00 and 12:00 AM Results: The measurements established that no significant association existed between the TAS level of colostrum and parity, maternal age, or infant sex. However, mothers 18 to 30 years of age had significantly lower colostrum TOS and OSI levels compared with mothers older than 30 years of age. IgA and IgM values of the colostrum of primiparous mothers were significantly higher than those of multiparous mothers, whereas no correlations existed with the age of the mother. Additionally, significantly higher colostrum IgA and IgM values were observed in female infants fed colostrum compared with male infants. Conclusion: In conclusion, sex-based hormonal changes in mothers during pregnancy may be associated with the different colostral immunoglobulin levels for male and female infants.

Relationship of fibroblast growth factor 21, sirtuin 1, visfatin, and regulators in children with short stature.

Fibroblast growth factor 21 (FGF21) is mainly secreted by the liver. It is a factor that is not fully understood in relation to growth. Sirtuin 1 (SIRT1) is a deacetylase protein. It is thought that may have an effect on the release and function of GH and IGF-1. Visfatin is synthesized from adipose tissue as primary. It may be prognostic marker associated with growth factors. As a result of our work, FGF21 is not associated with short stature but levels of SIRT1 and visfatin are associated with short stature. The decrease in visfatin value in the short-stature group is thought to be due to an insufficient amount of adipose tissue, which is important for growth and development. SIRT1 might decrease GH effect by increasing STAT5 deacetylation in the liver and we think that the result of this reduction of SIRT1 would negatively impact IGF-1 and IGFBP-3 production.

Effect of Blood Phenylalanine Levels on Oxidative Stress in Classical Phenylketonuric Patients.

Mental retardation, which occurs in phenylketonuric patients, is associated with increased levels of phenylalanine, increased oxidative stress, and an imbalance of amino acids in the brain. Recent studies have shown that oxidative stress plays a role in the pathogenesis of phenylketonuria. In this work, we aimed to compare the influence of blood phenylalanine levels on oxidative stress parameters in phenylketonuric patients who divided patients into groups according to blood Phe levels during follow-up visits and compared these groups with healthy controls. Results showed significant differences in glutathione peroxidase (GSHPx), coenzyme Q10 (Q10), Q10/cholesterol, and L-carnitine levels in phenylketonuria patients and the control group. GSHPx, Q10, and Q10/cholesterol levels were significantly lower in poor adherence patients than in the control groups. L-carnitine levels were significantly increased in good adherence patients than poor adherence patients and decreased in poor adherence patients than healthy controls. No correlations were observed between phenylalanine and L-carnitine concentrations in poor adherence group. No significant differences were observed in paraoxonase 1 (PON1), total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) levels. As a result, in this work, poor adherence patients are prone to oxidative stress. Although the patients may have the same diagnosis, patients have different clinical characteristics and different prognosis. Antioxidants can be used as an adjuvant therapy in order to avoid neurological damage in these patients.

The effects of bupivacaine combined with different adjuvants on block onset and duration and on ion channel expressions (SCN9A, TRPM) in sciatic nerve block in rats.

BACKGROUND/AIM: The objective of this experimental study was to examine the effects of epinephrine, dexmedetomidine, and clonidine added as adjuvants to bupivacaine on block onset and effect times, as well as the effects on the Na+ and Ca+2 channel gene expressions, which may indicate cell damage in the sciatic nerve cell membrane. MATERIALS AND METHODS: Rats were divided into five groups: Group S (sham), saline solution; Group B, bupivacaine; Group BD, bupivacaine + dexmedetomidine; Group BC, bupivacaine + clonidine; and Group BE, bupivacaine + epinephrine. For each group, 0.2 mL of local anesthetic was injected into the sciatic nerve bifurcation point of the right leg. Sensory (proprioceptive and nociceptive block) and motor block onset and ending times were recorded. RESULTS: The shortest onset time for the examined sciatic block was observed in the BC group, whereas the longest sensory and motor block times were observed in the BD group. The present data suggest suppressed TRPM7 and increased TRPM2 in the groups other than the BE group. CONCLUSION: Clonidine is more suitable for fast onset of peripheral nerve blocks, whereas the addition of dexmedetomidine is better in terms of duration. Because the SCN9A and TRPM2,4,7 expression ratios of the BE group showed the least amount of change, this group had the best cellular integrity.

Assessment of expressions of Bcl-XL, b-FGF, Bmp-2, Caspase-3, PDGFR-α, Smad1 and TGF-ß1 genes in a rat model of lung ischemia/reperfusion.

OBJECTIVES: Ischemia is described as organs and tissues are destitute of oxygen due to decreased arterial or venous blood flow. Many mechanisms play role in cell death happened as a consequence of a new blood flow is needed for both cell regeneration and to clean toxic metabolites during ischemia and later. Lung damage induced by ischemia/reperfusion (I/R) is a frequent problem in lung transplantation. Apoptosis (programmed cell death) is known as cell suicide, and plays a key role in embryonic developmental and in maintain adult tissue's life. MATERIALS AND METHODS: It is investigated expressions of Smad1, Bmp-2, Bcl-XL, b-FGF, Caspase-3, TGF-ß1, PDGFR-α genes for molecular changes in lung tissues, after I/R is formed, in this study. For this, we included 40 Wistar albino rats to this study and divided 4 groups (n=10). The Groups were determined as Control (C), Group 1= 1 hr ischemia (I), Group 2= 1 hr ischemia+2 hr reperfusion (I+2R), Group 3= 1 hr ischemia+4 hr reperfusion (I+4R). Besides, molecular analysis and histopathologic examinations of tissues were performed, and the results were evaluated by normalization and statistics analysis. RESULTS: We have found a significant increase in expression of Bcl-XL (P=0.046) and Caspase-3 (P=0.026) genes of group 1, and it was not monitored any significant difference in Group 2 and Group 3. In all groups, the changes in b-FGF (P=0.087), Bmp-2 (P=0.457), TGF-ß1 (P=0.201) and PDGFR-α (P=0.116) were not significant compared to control group. We did not see any mRNA expression of Smad1 gene in all groups include control. CONCLUSION: These findings suggest that I/R injury may trigger apoptotic mechanism in lung.

Palosuran treatment effective as bosentan in the treatment model of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive and fatal disorder that any valuable advance in the management of diseases has crucial importance. The present study aimed to compare the Endothelin1 (ET1) inhibitor bosentan which is regarded as standard therapy with different dose regimens of palosuran which is urotensin-II (UII) inhibitor and explore the discrepancy for mean pulmonary arterial pressure (mPAP), UII, ET1 levels, and pulmonary vascular pathology. Seventy rats were randomly divided into seven groups of ten animals each: group 1 (control group) received the vehicle subcutaneously, instead of monocrotaline (MCT) and vehicle; group 2 (MCT group) received subcutaneous MCT and vehicle; and group 3 (MCT + palosuran 30 mg) received subcutaneous MCT and palosuran. Other groups consist of group 4 (MCT + palosuran 100 mg), group 5 (MCT + bosentan 30 mg), group 6 (MCT + bosentan 100 mg), and group 7 (combination therapy). Serum ET1, UII, mPAP levels, and pulmonary arteriolar pathology of different diameter vessels of all groups have been measured and recorded. The ET1 and UII levels of untreated rats (group 2) were significantly higher than the other groups (p < 0.05). Moreover, mPAP levels of group 2 were significantly higher than the other groups (p = 0.001). Finally, 50-125-µm diameter of arteriole wall thickness was found to be significantly thicker in monocrotaline group compared to groups 4 and 6 (p < 0.001). Statistical differences of wall thickness/diameter ratios of arteries and arterioles larger than 125 was found to be significant between group 5, group 6, and the control group (p < 0.001). UII inhibitor is at least as effective as standard therapy bosentan. Findings of this study consolidate that palosuran could be a new future promising therapeutic option in PAH.

Evaluation of TRPM (transient receptor potential melastatin) genes expressions in myocardial ischemia and reperfusion.

In the present study, the expression levels of TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, and TRPM8 genes were evaluated in heart tissues after ischemia/reperfusion (IR). For this study, 30 albino male Wistar rats were equally divided into three groups as follows: Group 1: control group (n:10), Group II: ischemia group (ischemia for 60 min) (n:10) and Group III: IR (reperfusion 48 h after ischemia for 60 min and reperfusion for 48 h). The expression levels of the TRPM genes were analyzed by semi-quantitative reverse transcriptase-PCR. When compared to the ischemia control, the expression levels of TRPM2, TRPM4, and TRPM6 did not change, whereas that of TRPM7 increased. However, TRPM1, TRPM3, TRPM5, and TRPM8 were not expressed in heart tissue. Histopathological analysis of the myocardial tissues showed that the structures that were most damaged were those exposed to IR. The findings showed that there is a positive relationship between TRPM7 expression and myocardial IR injury.

The role of hepcidin and its related genes (BMP6, GDF-15, and HJV) in rats exposed to ischemia and reperfusion.

BACKGROUND/AIM: To determine the roles of hepcidin and its related genes in a renal ischemia/reperfusion model. MATERIALS AND METHODS: A total of 20 Wistar albino rats were equally divided into 2 groups: Group I was the control group and Group II was the ischemia and reperfusion (I/R) group (60 min of ischemia + 48 h of reperfusion). I/R was performed on the left kidneys of these rats and then the I/R-treated kidneys were removed. The levels of serum biochemical markers were evaluated after renal I/R. The expression levels of hepcidin-linked genes [growth differentiation factor 15 (GDF-15), bone morphogenetic protein 6 (BMP6), and hemojuvelin (HJV)] were also measured by RT-PCR technique. In addition, the tissues were evaluated histopathologically. RESULTS: No significant association was found between renal dysfunction and I/R when compared to biochemical parameters (P > 0.05). However, differences in platelet values were statistically significant (P < 0.05). Expression levels of GDF-15, BMP6, and HJV genes increased, but this increase was not statistically significant. In addition, histopathological evaluation was performed using hematoxylin and eosin stain. This showed a significant relationship between the control group and I/R group for ischemic and nonischemic kidney scoring. CONCLUSION: Hepcidin and BMP6, HJV, and GDF-15 should be taken into account when investigating the process of I/R.

Investigation of the esophageal Rho-kinase expression in patients with Barrett's esophagus.

The mechanisms responsible for the malignant transformation in Barrett's esophagus (BE) are still poorly understood. The authors have evaluated the role of Rho-kinase (ROCK1 and ROCK2) expressions in patients with BE. All patients underwent upper gastrointestinal system endoscopy, which was confirmed histologically. Real-time PCR revealed no marked change in gene expressions of ROCK1 and ROCK2 at mRNA levels in BE when compared to controls. Immunohistochemical and western blot analyses showed no change in ROCK1 and ROCK2 protein expressions in BE. This study demonstrates that Rho-kinase gene and protein expressions are not modified in BE.

Preliminary study of efficacy of hyaluronic acid on caustic esophageal burns in an experimental rat model.

BACKGROUND: The aim of this study was to investigate the effectiveness of hyaluronic acid on the prevention of esophageal damage and stricture formation after experimental caustic (alkaline) esophageal injury in rats. MATERIALS AND METHODS: Twenty-one Wistar albino rats were randomly divided into three groups. A caustic esophageal burn was created following the Gehanno model: Group l (n=7) underwent operation, but no injury; Group 2 (n=7) was injured and left untreated; and Group 3 (n=7) was injured and treated with hyaluronic acid, first topically and then orally by gavage (2×0.3mL; 12.5mg/mL for 7days). The caustic esophageal burn was created by instilling 25% NaOH into the distal esophagus. All rats were euthanized on day 22 for evaluation. The efficacy of hyaluronic acid treatment was assessed histopathologically and biochemically via blood determination of the total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and sulfhydryl group (SH) and lipid hydroperoxidase (LOOH) levels. Statistical analyses were performed. RESULTS: Weight gain was significantly lower in Group 2 than in the other two groups (P<0.05). The mean stenosis index, histopathologic damage score, TAS, TOS, OSI, and SH and LOOH levels were higher in Group 2 than in the other two groups. The mean stenosis index, inflammation, TAS, SH and OSI in Group 2 were significantly different than those in the other two groups (P<0.05). CONCLUSION: Hyaluronic acid treatment is effective in treating damage and preventing strictures after caustic esophageal burn in rats.

Urotensin inhibition with palosuran could be a promising alternative in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive and a life-threatening disease with its high morbidity and mortality ratios. On searching for new shining targets in pathogenesis, we noticed, in our previous studies, urotensin-II (UII) in systemic sclerosis with potent angiogenic and pro-fibrotic features. Owing to the mimicking properties of UII with endothelin-1 (ET1), we attempted to investigate the effect of palosuran in a PAH rat model. Thirty rats were randomly divided into three groups, with each group comprising 10 rats: group 1 (control group) received the vehicle subcutaneously, instead of monocrotaline (MCT) and vehicle; group 2 (MCT group) received subcutaneous MCT and vehicle; and group 3 (MCT + palosuran group) received subcutaneous MCT and palosuran. Serum UII, ET1, transforming growth factor-ß1 (TGF-ß1) levels, pulmonary arteriolar pathology of different diameter vessels, and cardiac indices were evaluated. The ET1, TGF-ß1, and UII levels were significantly diminished in the treatment group, similar to the controls (p < 0.001). Right ventricular hypertrophy index and mean pulmonary arterial pressure scores were also significantly reduced in the treatment group (p = 0.001). Finally, in the 50-125-µm diameter arterioles, in contrast to Groups 3 and 1, there was a statistically significant thickness (p < 0.01) in the arteriolar walls of rats in Group 2. The treatment effect on arteries of more than 125-µm diameters was found to be valuable but not significant. Owing to its healing effect on hemodynamic, histological, and biochemical parameters of MCT-induced PAH, palosuran as an antagonist of UII might be an optional treatment alternative for PAH.

Effectiveness of palosuran in bleomycin-induced experimental scleroderma.

Systemic sclerosis (SSc) is a disease characterized by skin and internal organ involvement. There is progressive accumulation of extracellular matrix components in the skin and involved organs. Tissue fibrosis is the prominent reason for mortality, and still, there is no satisfactory treatment. The aim of this study was to evaluate the effects of urotensin-II (U-II) antagonist palosuran in an animal model of scleroderma. We also planned to measure U-II, endothelin-1 (ET-1), and transforming growth factor-ß1 (TGF-ß1) levels, as well as the association of these levels with dermal thickness. Twenty-four male mice were included in this study and they were divided into three groups--group 1: control group, group 2: fibrosis group, and group 3: fibrosis + palosuran treatment group. Fibrosis + palosuran treatment in group 3 reduced ET-1, U-II, and TGF-ß1 levels. In total, the diminished values were statistically significant in the ET-1 and TGF-ß1 levels (p < 0.05). Dermal thickness was higher in the fibrosis group, when compared with the other groups. There was no significant relationship between dermal thickness and ET-1, U-II, or TGF-ß1 levels (p > 0.05). It is believed that U-II is an important mediator in SSc, and its antagonism with palosuran could be a new treatment choice in SSc.

Prolidase could act as a diagnosis and treatment mediator in lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with unknown etiology and pathogenesis. With high mortality risks, most of the IPF cases emerged after a damage of alveolar epithelium, where this situation stimulates the over expression of matrix components. Inflammatory process observed as a reaction to emerged damage. Prolidase as an iminodipeptidase significantly increased during the development of fibrosis. The aim of this study is to measure prolidase activity as a marker of treatment and diagnosis in an experimental lung fibrosis animal model. Thirty male Wistar rats randomly divided into three experimental groups, with ten rats in each group. Group 1, control group; group 2, bleomycin (BLM)-induced lung fibrosis group, and group 3, BLM-induced lung fibrosis treated with palosuran (urotensin-II receptor antagonist). For histopathology, the middle lobes of right lungs were embedded in paraffin, followed by fixation in 10 % buffered formalin, and evaluation of IPF was performed using the Ashcroft scoring method. Prolidase activity was determined by a photometric method based on the measurement of proline levels produced by prolidase. The fibrosis scores and the prolidase activity were significantly enhanced by BLM stimulation. The BLM + palosuran treatment decreased prolidase activity in group 3. There was a positive correlation between prolidase activity and fibrosis scores. Palosuran seems to be effective in the treatment of lung fibrosis, and prolidase activity can be used for the diagnosis and/or for management of the treatment. However, further clinical and experimental studies with animals and/or patients are needed to verify these conclusions.