Estratificación del riesgo de fenoconversión al parkinsonismo en pacientes con trastorno de conducta del sueño REM aislado. Estudio de seguimiento en un centro de Turquía / Risk stratification for phenoconversion in patients with isolated REM sleep behavior disorder. A follow-up study from Turkey

Introducción El trastorno aislado de la conducta del sueño con movimientos oculares rápidos (iRBD) es uno de los marcadores prodrómicos más potentes de las alfa-sinucleinopatías. Nuestro objetivo fue investigar los predictores clínicos y cuan­titativos no invasivos de la fenoconversión de iRBD a parkinsonismo. Pacientes y métodos Se siguió prospectivamente a un total de 45 pacientes (57,8% hombres) durante ocho años del período de estudio. Se realizaron evaluaciones clínicas, la prueba de identificación de olores Sniffin’ Sticks, la prueba Farnsworth-Munsell 100 Hue Color Vision, el inventario de depresión de Beck y los criterios de Roma III para el estreñimiento. Se analizaron parámetros polisomnográficos, husos del sueño, análisis espectral electroencefalográfico (EEG) y variabilidad de la frecuencia cardíaca. Resultados Ocho pacientes (17,8%) mostraron fenoconversión a parkinsonismo después de una duración media de seguimiento de 3,2 ± 1 año. La odds ratio para predecir la fenoconversión fue más alta para los pacientes =60 años con anosmia y estreñimiento –44,8 (4,5-445,7); kappa = 4,291–. La disminución de la potencia del espectro EEG, junto con la edad =60 años, la anosmia y el estreñimiento, dio como resultado el índice de odds más alto –122,5 (9,7-1543,8); kappa = 3,051–. Conclusiones Es de gran importancia tener una perspectiva mundial de las tasas de fenoconversión de iRBD a neurodegeneración manifiesta, ya que los factores raciales y geográficos pueden desempeñar importantes papeles modificadores. Los biomarcadores neurofisiológicos parecen ser predictores importantes de la fenoconversión, aunque se necesita más investigación para establecer subtipos de iRBD con diferentes probabilidades de evolución hacia una sinucleinopatía manifiesta. (AU)

INTRODUCTION Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is one of the strongest prodromal markers of alpha-synucleinopathies. We aimed to investigate non-invasive clinical and quantitative predictors of phenoconversion from iRBD to parkinsonism. PATIENTS AND METHODS We prospectively followed-up a total of 45 patients (57.8% men) for eight years. Clinical assessments, Sniffin’ Sticks Odor Identification Test, Farnsworth-Munsell 100 Hue Color Vision test, Beck Depression Inventory and Rome III Criteria for constipation were performed. Polysomnographic parameters, sleep spindles, electroencephalographic (EEG) spectral analysis, heart rate variability (HRV) were analyzed. RESULTS Eight patients (17.8%) showed phenoconversion to parkinsonism after a mean duration of 3.2 ± 1 years. Odds ratio for predicting phenoconversion was highest for patients =60 years of age with anosmia and constipation –44.8 (4.5-445.7); kappa = 4.291–. Duration, frequency or density of sleep spindles failed to demonstrate significant correlations. In EEG spectral analysis, lower alpha power in occipital region during wakefulness and REM sleep was significantly correlated with phenoconversion. Slowing in EEG spectrum power, together with age =60 years, anosmia and constipation, resulted in the highest odds ratio –122.5 (9.7-1543.8); kappa = 3.051–. CONCLUSIONS It is of great importance to have a world-wide perspective of phenoconversion rates from iRBD to overt neurodegeneration, since racial and geographical factors may play important modifying roles. Relatively younger age and shorter disease duration may also be confounding factors for lower rate in our study. Neurophysiological biomarkers seem to be important predictors of phenoconversion, though more research is needed to establish subtypes of iRBD with different probabilities of evolution to overt synucleinopathy. (AU)

Sublingual Administration of Teucrium Polium-Loaded Nanofibers with Ultra-Fast Release in the Treatment of Diabetes Mellitus: In Vitro and In Vivo Evaluation.

In this study, Teucrium polium (TP) methanolic extract, which has antidiabetic activity and protects the ß-cells of the pancreas, was loaded in polyethylene oxide/sodium alginate nanofibers by electrospinning and administered sublingually to evaluate their effectiveness in type-2 diabetes mellitus (T2DM) by cell culture and in vivo studies. The gene expressions of insulin, glucokinase, GLUT-1, and GLUT-2 improved in TP-loaded nanofibers (TPF) on human beta cells 1.1B4 and rat beta cells BRIN-BD11. Fast-dissolving (<120 s) sublingual TPF exhibited better sustainable anti-diabetic activity than the suspension form, even in the twenty times lower dosage in streptozotocin/nicotinamide-induced T2DM rats. The levels of GLP-1, GLUT-2, SGLT-2, PPAR-γ, insulin, and tumor necrosis factor-alpha were improved. TP and TPF treatments ameliorated morphological changes in the liver, pancreas, and kidney. The fiber diameter increased, tensile strength decreased, and the working temperature range enlarged by loading TP in fibers. Thus, TPF has proven to be a novel supportive treatment approach for T2DM with the features of being non-toxic, easy to use, and effective.

Does total knee arthroplasty affect pelvic movements? A prospective comparative study.

OBJECTIVE: Pathology in any segment of the spine-pelvis-lower extremity may impair the global postural balance, leading to compensatory alterations in other parts. The aim of this study was to compare the pelvic movements of patients suffering from knee osteoarthritis with patients who underwent total knee arthroplasty and healthy controls. METHODS: This study was performed at the Department of Orthopedics and Traumatology Clinic of a Cankiri State Hospital between April 2021 and February 2022. This study included 84 participants. Of them, 31 patients who underwent total knee arthroplasty between 2018 and 2020 years were selected as the total knee arthroplasty group, while 28 patients with knee osteoarthritis were selected as the knee osteoarthritis group. In the control group, there were 25 healthy individuals. Exclusion criteria from the study included any kind of neurological disease, an inability to walk a distance of 100 m unassisted, or a history of surgery to the lower limb. Pelvic movements (i.e., tilt, rotation, and obliquity) and gait parameters (i.e., "gait velocity," "cadence," and "stride length") were assessed using a wireless tri-axial accelerometer. RESULTS: Total knee arthroplasty and control groups had decreased minimum anterior tilt of the pelvis, decreased maximum anterior tilt, and decreased oblique range of the pelvis compared with the knee osteoarthritis group. In comparison with the control group, gait velocity and length of stride during gait were remarkably lower in both knee osteoarthritis and total knee arthroplasty groups. CONCLUSION: In this study, total knee arthroplasty was found to affect pelvic movements. It was thought that total knee arthroplasty changed these variables, probably owing to the frontal and sagittal plane alignment correction through surgery.

Does total knee arthroplasty affect pelvic movements? A prospective comparative study

SUMMARY OBJECTIVE: Pathology in any segment of the spine-pelvis-lower extremity may impair the global postural balance, leading to compensatory alterations in other parts. The aim of this study was to compare the pelvic movements of patients suffering from knee osteoarthritis with patients who underwent total knee arthroplasty and healthy controls. METHODS: This study was performed at the Department of Orthopedics and Traumatology Clinic of a Cankiri State Hospital between April 2021 and February 2022. This study included 84 participants. Of them, 31 patients who underwent total knee arthroplasty between 2018 and 2020 years were selected as the total knee arthroplasty group, while 28 patients with knee osteoarthritis were selected as the knee osteoarthritis group. In the control group, there were 25 healthy individuals. Exclusion criteria from the study included any kind of neurological disease, an inability to walk a distance of 100 m unassisted, or a history of surgery to the lower limb. Pelvic movements (i.e., tilt, rotation, and obliquity) and gait parameters (i.e., "gait velocity," "cadence," and "stride length") were assessed using a wireless tri-axial accelerometer. RESULTS: Total knee arthroplasty and control groups had decreased minimum anterior tilt of the pelvis, decreased maximum anterior tilt, and decreased oblique range of the pelvis compared with the knee osteoarthritis group. In comparison with the control group, gait velocity and length of stride during gait were remarkably lower in both knee osteoarthritis and total knee arthroplasty groups. CONCLUSION: In this study, total knee arthroplasty was found to affect pelvic movements. It was thought that total knee arthroplasty changed these variables, probably owing to the frontal and sagittal plane alignment correction through surgery.

The effects of tarantula cubensis extract on renal ischemia reperfusion injury in rats.

BACKGROUND: Renal ischemia-reperfusion (IR) related acute kidney injury (AKI) is an important health problem and has not yet been fully treated. Tarantula cubensis extract (TCE) is a homeopathic drug that has antiinflammatory and antioxidant effects. This study aimed to investigate the effects of TCE on renal ischemia-reperfusion injury in rats. METHODS: This study was carried out on 48 Spraque-Dawley male rats, which were divided into six groups. The first, second, and third groups were control, sham, and IR groups, respectively. Group four received IR and 0.2 mL of 96% ethanol. Group five and six received ischemia and reperfusion and TCE 0.01 and 0.1 mg per rat (which correspond to approximately 0.04 mg/kg, and 0.4 mg/kg), respectively. Tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1ß), total antioxidant status (TAS), and total oxidant status (TOS) levels in renal tissue were measured by enzyme-linked immunosorbent assay (ELISA). Oxidative stress index (OSI) was obtained by proportioning TAS and TOS. Superoxide dismutase (SOD), myeloperoxidase (MPO) activities, and malondialdehyde (MDA) levels were determined by manual spectrophotometric methods. The histopathological changes were evaluated via hematoxylineosin and immunohistochemical staining. RESULTS: In IR group, renal tissue TNF-α and IL-1ß levels were significantly higher than control group (p < 0.0001 for both), and low(p < 0.0001 for both) and high dose (p < 0.0001 for both) TCE administration decreased these markers. Low and high doses of TCE decreased OSI values compared with IR group (p = 0.04 and p = 0.001 respectively). Although TCE decreased MDA levels, it was not statistically significant. MPO levels significantly decreased. In addition, TCE has been found to prevent hemorrhage, cast formation, and dilatation caused by IR in renal tissues stained with hematoxylin-eosin. And also, the most intense nuclear factor kappa B (NFκB) and caspase-3 immunopositivity found in IR group was decreased in both of the TCE groups. DISCUSSION: Although TCE showed a protective effect by inhibiting inflammation against IR damage in renal tissues, there was no clear effect on oxidative stress. Larger and more detailed studies are needed to clarify the issue.

Whether to flip Extreme Apprenticeship: which is more effective in programming instruction?

Programming knowledge is more important than ever in the digital world. However, teaching programming can be challenging, especially with novice learners. Considerable research has been conducted into the most effective methods for teaching programming. Extreme apprenticeship, a variation of cognitive apprenticeship, is a method that has been used in teaching programming at university level in recent years. Because this method focuses particularly on completing lots of exercises with coaching and guidance, it may solve many problems related to learning programming. Flipped learning can be useful for student preparedness and providing sufficient theoretical knowledge at the beginning of the course. This study compares the applications of the extreme apprenticeship method, flipped extreme apprenticeship, and traditional classroom, analyzing them at the university level in terms of their effects on academic achievement and engagement coupled with gender differences. The findings of the study indicate that the extreme apprenticeship and flipped extreme apprenticeship instructional methods improve academic achievement and student engagement in introductory programming more than the traditional method. The results of the research point to important directions for the development of the extreme apprenticeship method in programming instruction and provide a guide for instructors. Supplementary Information: The online version contains supplementary material available at 10.1007/s10639-022-11055-y.

Therapeutic effects of apocynin on ovarian ischemia-reperfusion induced lung injury.

Ovarian ischemia-reperfusion (I-R) injury may damage remote organs, including the lungs. We investigated whether apocynin, a NADPH oxidase inhibitor, might protect against ovarian I-R induced apoptosis in the lungs of rats. Bilateral ovarian I-R was induced for 3 h, then apocynin was applied at two concentrations. Lung tissue was evaluated using spectrophotometric and immunohistochemical methods. We found that I-R increased total oxidant status (TOS), oxidative stress index (OSI) and myeloperoxidase (MPO) levels, and immunostaining of nuclear factor kappa-B (NF-κB), light chain 3B (LC3B), interleukin 1-beta (IL-1ß), caspase-3 and tumor necrosis factor-alpha (TNF-α), but decreased superoxide dismutase (SOD) values. Apocynin application to I-R injured rats enhanced recovery of lung tissue oxidants and improved both histology and frequency of apoptosis.

In vitro and in vivo evaluation of 3D printed sodium alginate/polyethylene glycol scaffolds for sublingual delivery of insulin: Preparation, characterization, and pharmacokinetics.

Delivery of therapeutic peptides via sublingual administration is extremely desired and 3D printed scaffolds are potential candidates as carriers to enhance insulin delivery. 3D printed sublingual sodium alginate (SA)/polyethylene glycol (PEG) composite scaffolds were produced for enhancing insulin delivery by examining the chemical, morphological, mechanical, thermal, cytotoxic, and pharmacokinetic features. The tensile strength and flexibility of scaffolds increased after loading insulin due to the crystalline structure of insulin. Furthermore, insulin-loaded 9SA/3PEG scaffolds showed ultrafast wetting (<1 s), disintegration (<6 s), and also dissolution (<30 s) according to Hixson-Crowell kinetic model. The cell viability of L929 cells on 3D printed scaffolds was examined and these scaffolds could be safely applied on animals. Pharmacokinetic parameters and blood glucose level were evaluated following sublingual administration of scaffolds to type-1 diabetic rats. A single dose of scaffold presented a longer hypoglycemic effect, reducing ~60% of glycemia after 30 min and it lasted for 12 h by increasing the bioavailability of insulin. Scaffolds indicated a sustained profile for serum insulin levels, which continued to increase slightly after 3 h during the study. The polymeric scaffold with a high safety and efficacy holds a new promising delivery strategy for administering injectable insulin through the sublingual route.

Urapidil alleviates ovarian torsion detorsion injury via regulating oxidative stress, apoptosis, autophagia, and inflammation.

OBJECTIVES: This study aimed to determine anti-inflammatory, antioxidant, and antiapoptotic properties of urapidil (Ura) against ovarian torsion detorsion (T/D) injury in rats. MATERIALS AND METHODS: 40 female Wistar albino rats were grouped as sham, T/D, T/D+dimethyl sulfoxide (DMSO), T/D+Urapidil (Ura) 0.5 mg/kg (low dose), and T/D+Urapidil (Ura) 5 mg/kg (high dose) groups. In treatment groups, Ura was administered intraperitoneally just before detorsion. Biochemical parameters (TAS, TOS, MDA, MPO, and SOD) and immunohistochemical (IL-1ß, TNF-α, NF-κB, LC3B, and Caspase-3) analyzes were performed. RESULTS: In the T/D group, OSI and MPO levels were elevated significantly while TAS values decreased compared with the sham group. A significant difference occurred in the low dose treatment group in TAS and OSI levels compared with the T/D group. In the high dose treatment group, significant elevation in TAS but reduction in OSI and MDA levels were observed compared with the T/D group. Immunohistochemical staining resulted in IL-1ß, TNF-α, NF-κB, LC3B, and caspase-3 immunopositivity in the T/D group, while Ura treatment decreased those parameters. Intensive congestion and hemorrhage were observed in the T/D group, but contrary to this, treatment groups had alleviated congestion and hemorrhage. CONCLUSION: These results suggest that Ura demonstrated protective effects against ovarian T/D injury via anti-oxidative, anti-inflammatory, and anti-apoptotic features.

Royal jelly attenuates gastric mucosal injury in a rat ethanol-induced gastric injury model.

The aim of the study was to investigate traditionally used Royal Jelly (RJ) for treating an ethanol-induced gastric ulcer model in rats. A total of 32 Wistar albino male rats were divided into 4 groups of 8: group I = Control, group II = Ethanol, group III = RJ + Ethanol, and group IV = Lansoprazole + Ethanol. In groups II, III, and IV, animals were administered 1 ml of absolute ethanol orally after a 24-h fast to induce ulcer formation. The histopathological changes in the gastric mucosa were determined using hematoxylin-eosin (H&E) staining. Immunohistochemically, inducible nitric oxide (iNOS) and nuclear factor kappa beta (Nf-κß) markings were evaluated in gastric tissue. Cell death in the gastric mucosa was determined by the TUNEL method. Oxidative status markers, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and myeloperoxidase (MPO) levels were determined spectrophotometrically. Expression of the interleukin - 1 beta (IL-1ß) and tumor necrosis factor-α (TNF-α) genes in gastric tissues was determined by real-time PCR; and TNF-α, IL-10, and IL-1ß levels were determined. RJ was found to inhibit iNOS and Nf-κß activity in the gastric mucosa and prevent epithelial cell apoptosis. In particular, pro-inflammatory cytokines TNF-α and IL-1ß levels were significantly decreased in the RJ + Ethanol group compared to the Ethanol group. In addition, a decrease in the MPO level indicated that RJ prevented tissue damage, especially by preventing inflammatory cell infiltration. The study demonstrated a possible gastroprotective effect of RJ in a rat ethanol-induced gastric ulcer model.

Protective Effect of Lycopene against Reperfusion Injury in Rats with Ovarian Torsion: A Biochemical and Histopathological Evaluation.

Objective The aim of our study was to evaluate the effect of two different doses of lycopene, an antioxidant, on experimentally induced ovarian ischemia/reperfusion (IR) injury in rat model. Materials and Methods Twenty-four female rats were randomly divided into four groups: sham operation (group 1), 3-hour ischemia, 3-hour reperfusion (IR) (group 2), and IR + 100 mg/kg lycopene (PO) (group 3), IR + 200 mg/kg of lycopene (group 4). The rats' superoxide dismutase (SOD), myeloperoxidase (MPO) activities, malondialdehyde (MDA), and glutathione (GSH) levels were calculated. Ovarian tissue damage was assessed using a histopathological scoring system. Results Serum parameter levels and histological scores showed that treatment with lycopene may be conservative approach to prevent IR injury after the ovarian detorsion procedure.The improvement with lycopene was higher at 200 mg than at 100 mg. The MPO and MDA values were significantly lower in groups 3 and 4 as compared with group 2 ( p < 0.05), whereas the MPO and MDA values were lower in group 4 as compared with group 3.The SOD and GSH values were significantly higher in groups 3 and 4 as compared with group 2 ( p < 0.05), whereas the SOD and GSH values were higher in group 4 as compared with group 3.Tissue damage scores were elevated in the IR group compared with the sham group, but the treatment with different lycopene doses after reperfusion improved the histopathological tissue damage scores. Conclusion The results showed that lycopene treatment reduced ovarian IR damage. Antioxidant activity was found to increase in a dose-dependent manner. Lycopene treatment may be conservative approach for ovarian torsion patients after the detorsion procedure to prevent IR damage.

Evodiamine alleviates kidney ischemia reperfusion injury in rats: A biochemical and histopathological study.

Renal ischemia/reperfusion (I/R) injury resulting in acute renal failure, is a major clinical problem due to its high mortality rate. Renal I/R increases the reactive oxygen species, secretion of inflammatory cytokines, chemokines and other factors. This suggests that initiating the apoptosis process in the presence of oxidative stress may play a role in life-threatening conditions, such as ischemia. Ischemia reperfusion-induced renal damage can result in renal failure and death. Although many treatment procedures have been carried out to reduce or destroy renal I/R damage in experimental models, so far, a routine method of treatment has not yet been found. For this reason, the current study was planned to investigate the possible protective effects of evodiamine on tissue damage caused by ischemia-reperfusion in kidney tissue in rats and an experimental renal I/R model was used for this purpose. Four groups were formed in the study: the control, sham control, ischemia reperfusion (I/R), and evodiamine (10 mg/kg) + I/R groups. The effects of evodiamine against kidney I/R injury were investigated. TAS (total oxidant status), TOS (total oxidant status), interleukin-1ß (IL-1ß), IL-6, IL-10 and tumor necrosis factor-α levels were determined by enzyme-linked immunosorbent assay. The oxidative stress index was calculated from TAS and TOS levels. In addition, the renal ischemia reperfusion injury was examined histopathologically. The IL-10 and TAS levels in the I/R group decreased when compared with the control and Sham groups, while these levels increased in the evodiamine group. Histopathologic examination revealed that caspase 3 and nuclear factor-κB levels decreased in the evodiamine group compared with the I/R group. The application of evodiamine significantly reduced ischemia reperfusion-induced kidney damage due to its antioxidant, anti-inflammatory and antiapoptotic properties.

Protective effects of hesperetin on lipopolysaccharide-induced acute lung injury in a rat model.

BACKGROUND: In this experimental study, we aimed to investigate the effects of hesperetin, a natural flavonoid, on a lipopolysaccharideinduced acute lung injury model in rats. METHODS: Between March 2019 and May 2019, a total of 18 adult male Wistar albino rats, weighing approximately 250 to 300 g, were randomly divided into three groups as control, lipopolysaccharide, and lipopolysaccharide + hesperetin groups (n=6 in each group). The wet/dry weight ratio of lung tissue was determined. Histopathological changes were examined using light and scanning electron microscopy. Pulmonary nuclear factor-kappa beta, inducible nitric oxide synthase, and alpha-smooth muscle antigen activity were determined with indirect immunohistochemical methods. Pulmonary apoptosis was detected with the terminal deoxynucleotidyl transferase dUTP nick-end labeling method. Tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interleukin-10 concentrations were measured with enzyme-linked immunosorbent assay. RESULTS: Treatment with hesperetin significantly improved the architecture of lung tissue and reduced the wet/dry weight ratio, nuclear factor-kappa beta, inducible nitric oxide synthase, and alphasmooth muscle antigen expression, pulmonary apoptosis, and levels of proinflammatory cytokines. CONCLUSION: Our study results suggest that hesperetin has a potent protective effect against lipopolysaccharide-induced acute lung injury in rats via suppression of the proinflammatory cytokine cascade, nuclear factor-kappa beta, signaling pathway activation, and apoptosis.

8-Br-cADPR, a TRPM2 ion channel antagonist, inhibits renal ischemia-reperfusion injury.

The transient receptor potential melastatin-2 (TRPM2) channel belongs to the transient receptor potential channel superfamily and is a cation channel permeable to Na+ and Ca 2+ . The TRPM2 ion channel is expressed in the kidney and can be activated by various molecules such as hydrogen peroxide, calcium, and cyclic adenosine diphosphate (ADP)-ribose (cADPR) that are produced during acute kidney injury. In this study, we investigated the role of 8-bromo-cyclic ADP-ribose (8-Br-cADPR; a cADPR antagonist) in renal ischemia-reperfusion injury using biochemical and histopathological parameters. CD38, cADPR, tumor necrosis factor-α, interleukin-1ß, and myeloperoxidase (inflammatory markers), urea and creatinine, hydrogen peroxide (oxidant), and catalase (antioxidant enzyme) levels that increase with ischemia-reperfusion injury decreased in the groups treated with 8-Br-cADPR. In addition, renin levels were elevated in the groups treated with 8-Br-cADPR. Histopathological examination revealed that 8-Br-cADPR reduced renal damage and the expression of caspase-3 and TRPM2. Our results suggest that the inhibition of TRPM2 ion channel may be a new treatment modality for ischemic acute kidney injury.

The potential role of amlodipine on experimentally induced bacterial rhinosinusitis / O papel potencial da amlodipina na rinossinusite bacteriana induzida experimentalmente

Abstract Introduction: Antibiotics are frequently used for the treatment of rhinosinusitis. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of development of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. Objective: In this study we aimed to investigate the potential role of amlodipine in the treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. Methods: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was composed by five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione) and an oxidative product (malondialdehyde) were determined. Results: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline) and although not superior to cefazolin, amlodipine decreased polymorphonuclear leukocyte infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. Conclusion: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.

Resumo Introdução: Antibióticos são frequentemente usados para o tratamento de rinossinusite. Questões têm sido levantadas sobre os efeitos adversos dos antibióticos e a resistência crescente. A falta de desenvolvimento de novos compostos antibióticos aumentou a necessidade da exploração de compostos não antibióticos que têm atividade antibacteriana. A amlodipina é um composto não antibiótico com atividade anti-inflamatória. Objetivo: O objetivo desse estudo foi investigar o papel potencial da amlodipina no tratamento da rinossinusite, avaliando seus efeitos sobre o estado oxidativo do tecido, histologia da mucosa e inflamação. Método: Quinze cobaias albinas adultas foram inoculadas com Staphylococcus aureus e tratadas com solução salina, cefazolina ou amlodipina durante sete dias. O grupo controle incluiu cinco cobaias saudáveis. Os animais foram sacrificados após o tratamento. Alterações histopatológicas foram identificadas com a coloração de hematoxilina-eosina. A inflamação foi avaliada pela densidade de infiltração de leucócitos polimorfonucleares. Foram determinados os níveis teciduais de antioxidantes (superóxido dismutase, glutationa) e um produto de oxidação (malondialdeído). Resultados: Em animais com rinossinusite induzida, a amlodipina reduziu a perda dos cílios, edema da lâmina própria e deposição de colágeno em comparação com o grupo placebo (solução salina) e embora não seja superior à cefazolina, a amlodipina diminuiu a infiltração de leucócitos polimorfonucleares. Os níveis de atividade da superóxido dismutase e glutationa foram reduzidos, enquanto os níveis de malondialdeído aumentaram significativamente nos três grupos de tratamento em comparação ao grupo controle. O grupo tratado com amlodipina apresentou aumento significante dos níveis de superóxido dismutase e glutationa e diminuição dos níveis de malondialdeído em comparação com todos os grupos de tratamento. Conclusão: O composto não antibiótico amlodipina pode ter um papel no tratamento da rinossinusite aguda através de mecanismos protetores de tecido, antioxidantes e anti-inflamatórios.

Protective effect of salusin-α and salusin-ß against ethanol-induced gastric ulcer in rats.

BACKGROUND: Alcohol consumption has been found to be associated with gastric ulcers, including gastric mucosal lesions. Salusin-α and salusin-ß are bioactive peptides having 28 and 20 amino acids, respectively. Salusin-α and salusin-ß immunoreactivity has been detected in the stomach and in the intestines. It has been reported that the salusins regulate the cytokine levels and decrease the infarct area in the heart tissue after ischemia. In this study, we investigated the effects of the salusins in the gastric injury formed with ethanol. METHODS: Thirty-two sprague Dawley male rats were randomly divided into four groups, including eight rats in each group as follows: Group 1: control; Group 2: ethanol 5 mL/kg; Group 3: ethanol 5 mL/kg+5 nmol/kg salusin-α; Group 4: ethanol 5 mL/kg+5 nmol/kg salusin-ß. RESULTS: The salusin-α level increased at a significant level in the ulcer group formed with ethanol (p<0.001); the change in the salusin-ß level is not significant. As for malondialdehyde (p<0.05) and myeloperoxidase (p<0.001), when compared with the control group, tumor necrosis factor-α (p<0.05) levels increased in the group to which ethanol was applied and decreased significantly with the application of salusins. Levels of GSH and IL-1ß did not change at a significant level. In addition, histopathologic analysis demonstrated that, in salusin-administered groups, mucosal injury and caspase-3 expressions were reduced. CONCLUSIONS: The suppression of salusin-α and salusin-ß on caspase-3 expression by means of their effects on oxidative injury and TNF-α levels shows that these two hormones could serve as anti-ulcerative agents.

The potential role of amlodipine on experimentally induced bacterial rhinosinusitis.

INTRODUCTION: Antibiotics are frequently used for the treatment of rhinosinusitis. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of development of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. OBJECTIVE: In this study we aimed to investigate the potential role of amlodipine in the treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. METHODS: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was composed by five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione) and an oxidative product (malondialdehyde) were determined. RESULTS: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline) and although not superior to cefazolin, amlodipine decreased polymorphonuclear leukocyte infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. CONCLUSION: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.

Comparison of Cobas 6500 and Iris IQ200 fully-automated urine analyzers to manual urine microscopy.

INTRODUCTION: Urine screening is achieved by either automated or manual microscopic analysis. The aim of the study was to compare Cobas 6500 and Iris IQ200 urine analyzers, and manual urine microscopic analysis. MATERIALS AND METHODS: A total of 540 urine samples sent to the laboratory for chemical and sediment analysis were analyzed on Cobas 6500 and Iris IQ200 within 1 hour from sampling. One hundred and fifty three samples were found to have pathological sediment results and were subjected to manual microscopic analysis performed by laboratory staff blinded to the study. Spearman's and Gamma statistics were used for correlation analyses, and the McNemar test for the comparison of the two automated analyzers. RESULTS: The comparison of Cobas u701 to the manual method yielded the following regression equations: y = - 0.12 (95% CI: - 1.09 to 0.67) + 0.78 (95% CI: 0.65 to 0.95) x for WBC and y = 0.06 (95% CI: - 0.09 to 0.25) + 0.66 (95% CI: 0.57 to 0.73) x for RBC. The comparison of IQ200 Elite to manual method the following equations: y = 0.03 (95% CI: - 1.00 to 1.00) + 0.88 (95% CI: 0.66 to 1.00) x for WBC and y = - 0.22 (95% CI: - 0.80 to 0.20) + 0.40 (95% CI: 0.32 to 0.50) x for RBC. IQ200 Elite compared to Cobas u701 yielded the following equations: y = - 0.95 (95% CI: - 2.13 to 0.11) + 1.25 (95% CI: 1.08 to 1.44) x for WBC and y = - 1.20 (95% CI: - 1.80 to -0.30) + 0. 80 (95% CI: 0.55 to 1.00) x for RBC. CONCLUSIONS: The two analyzers showed similar performances and good compatibility to manual microscopy. However, they are still inadequate in the determination of WBC, RBC, and EC in highly-pathological samples. Thus, confirmation by manual microscopic analysis may be useful.

Preventative Effect of Vitamin E on Mast Cells in Carbon Tetrachlorideinduced Acute Liver Damage.

BACKGROUND: Preventing liver damage that might lead to cirrhosis is very important in the early stages of injury to that organ. The role of mast cells (MCs) in liver injuries has been long debated, and vitamin E is a well-known antioxidant used to treat those injuries. This study aimed to determine the protective role of vitamin E on MCs in injury to the liver that is triggered by carbon tetrachloride (CCl4). There is a correlation between MC deposits and improvement in fibrosis tissues. METHODS: To further examine this, 68 male Albino Wistar rats were divided randomly into five groups: the control group, the vitamin E group, the CCl4 group, the CCl4 + vitamin E group, and the vitamin E + CCl4 group. Malondialdehyde (MDA) analysis, MC counts, histopathological investigation, and statistical analyses were used to evaluate the findings. RESULTS: The administration of CCl4 resulted in an increase in the accumulation of MCs, degenerative parenchyma cells, MDA level, steatosis and inflammation. Additionally, proliferation of the bile ducts in the portal area and porto-portal and porto-central fibrosis were observed in the CCl4 group. In contrast, in the vitamin E group and in the groups administered a combination of vitamin E and CCl4, vitamin E prevented these increases. CONCLUSION: It was concluded that the significant decrease in the MC counts, in the level of MDA and the number of degenerative cells, as well as a decrease in the steatosis and inflammation scores showed that vitamin E could prevent liver injuries by protecting the organ's histological architecture. Finally, the results indicate that vitamin E has positive effects on liver injuries.

Serum apelin and ADMA levels in type 2 diabetics with and without vascular complications.

AIMS: Type 2 diabetes mellitus (T2DM) is a metabolic and chronic disease which is characterized by hyperglycemia, and that is the major causes of various micro and macrovascular complications. Asymmetrical dimethylarginine (ADMA), formed by the hydrolysis of proteins containing methylated arginine residues, is an endogenous inhibitor of nitric oxide synthase (NOS), which oxidize l-arginine to citruline and nitric oxide (NO), related to hyperinsulinaemia and hyperlipidaemia. Apelin is a recently discovered peptide, present in a number of tissues and play role in insulin sensitivity improvement. In this study, our aim was to determine the levels of apelin and ADMA with glycated haemoglobin (HbA1c) in type 2 diabetic patients with or without vascular complications. METHODS: This study included (a total of) 59 diabetic patients. Of the patients, 30 were diabetic with complications, and 29 without complications. In serum samples obtained from the patients, serum ADMA and apelin levels were measured with Enzyme Linked Immunosorbent Assay (ELISA) method. RESULTS: Our study totally enrolled 59 patients in two groups. No significant differences were found in sex, age, HbA1c and glucose levels among groups. Apelin and ADMA levels of group with complications were lower than those of group without complications, but no statistically significant difference of apelin and ADMA levels (p>0.05). CONCLUSION: The results of this study have been showed no statistically significant relationship present between ADMA-apelin levels and complications of T2DM. Further studies involving larger patients populations and healthy controls should be done to clarify the pathogenetic significance of apelin and ADMA in diabetic vascular complications.