Chloroquine attenuates chronic hypoxia-induced testicular damage via suppressing endoplasmic reticulum stress and apoptosis in experimental rat model.

Chronic hypoxia negatively affects male fertility by causing pathological changes in male reproductive system. However, underlying mechanisms of this damage are unknown. Chloroquine (CLQ) is an anti-inflammatory agent that is widely used in the treatment of inflammation-related diseases such as malaria and rheumatoid arthritis. This study aimed to investigate the therapeutic effects of CLQ in the hypoxia-induced testicular damage via assessment of hypoxic response, endoplasmic reticulum stress and apoptosis. For this purpose, 32 Wistar albino rats were divided into 4 groups as control (given 20%-21% O2 , no treatment), CLQ (given 50 mg/kg and 20%-21% O2 for 28 days), hypoxia (HX) (given 10% O2 for 28 days) and HX + CLQ (given 50 mg/kg and 10% O2 for 28 days). After the experiment, blood samples and testicular tissues were taken. Histopathological evaluation was performed on testicular tissues and hypoxia-inducible factor 1-α (HIF1-α), heat shock proteins (HSPs) HSP70, HSP90 and growth arrest and DNA damage-inducible gene 153 (GADD153) expression levels were detected via immunohistochemistry. Moreover, apoptotic cells were detected via terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining and serum testosterone levels were determined by enzyme-linked immunosorbent assay (ELISA) assay. Histopathological changes, apoptotic cell numbers and HIF1-α, HSP70, HSP90 and GADD153 expressions significantly increased in HX group (P < .05). Moreover, serum testosterone levels decreased in this group (P > .05). However, CLQ exerted a strong ameliorative effect on all parameters in HX + CLQ group. According to our results, we suggested that CLQ can be considered as an alternative protective agent for eliminating the negative effects of hypoxic conditions on male fertility.

Thymoquinone attenuates doxorubicin-cardiotoxicity in rats.

Contrary to the fact that doxorubicin is a powerful chemotherapeutic agent for the treatment of neoplastic diseases, cardiotoxicity is too important to be ignored. Thymoquinone serves as a powerful free radical scavenger. In the study, the effects of thymoquinone against doxorubicin-cardiotoxicity will be evaluated. Forty rats were divided into five groups. Group I: control group (n = 8); group II: olive oil group (n = 8); group III: thymoquinone group (n = 8); given 10 mg/kg thymoquinone intraperitoneally per day throughout the experiment; group IV: doxorubicin group (n = 8); injected with a single dose of 15 mg/kg ip doxorubicin on the 7th day of the experiment; group V: doxorubicin + thymoquinone group (n = 8); administered with 10 mg/kg thymoquinone per day during the experiment and 15 mg/kg doxorubicin ip on the 7th day. The experiment was planned for 14 days. Immunohistochemically, heat shock protein (HSP) 70 and HSP90, glucose-regulated protein 78 (GRP78), caspase-3 were stained. We made terminal deoxynucleotidyl transferase dUTP nick end labeling for apoptotic evaluation. Total oxidant status (TOS) levels and total antioxidant status (TAS) were measured in the heart tissue. Atrial natriuretic peptide (ANP) and pro-B type natriuretic peptide (proBNP) were evaluated. In the study, HSP70, HSP90, GRP78, and caspase-3 levels increased in group IV. TOS and TAS levels were significant compared to group I. Doxorubicin significantly increased ANP and NT-proBNP levels. Thymoquinone revealed significant differences in these values. Thymoquinone can be an important cardioprotective agent against doxorubicin-cardiotoxicity.

Thymoquinone has a neuroprotective effect against inflammation, oxidative stress, and endoplasmic reticulum stress in the brain cortex, medulla, and hippocampus due to doxorubicin.

Although doxorubicin (DOX) is used in many cancer treatments, it causes neurotoxicity. In this study, the effect of thymoquinone (THQ), a powerful antioxidant, on DOX-induced neurotoxicity was evaluated. In total, 40 rats were used and 5 groups were formed. Group I: control group (n = 8); Group II: olive oil group (n = 8); Group III: the THQ group (n = 8); THQ 10 mg/kg per day was given intraperitoneally (i.p.) throughout the experiment; group IV: DOX group (n = 8); On Day 7 of the experiment, a single dose of 15 mg/kg intraperitoneally DOX injected; group V: DOX + THQ group (n = 8); Throughout the experiment, 10 mg/kg THQ per day and intraperitoneally 15 mg/kg DOX on Day 7 were injected. Immunohistochemically, tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), hypoxia-inducible factor 1α (HIF1-α), glucose regulatory protein 78 (GRP78), and the gene inducible by growth arrest and DNA damage 153 (GADD153) proteins were evaluated in the brain cortex, medulla, and hippocampus regions. Total oxidant status (TOS) levels and total antioxidant status (TAS) in the brain tissue were measured. TNF-α, IL-17, HIF1-α, GRP78, and GADD153 immunoreactivities significantly increased in the DOX group in the study. THQ significantly reduced these values. THQ increased the TAS level significantly and decreased the TOS level significantly compared to the DOX group. THQ may play a role as a neuroprotective agent in DOX-induced neurotoxicity in the cortex, medulla, and hippocampus regions of the brain.

A synthetic approach to novel carvotacetone and antheminone analogues with anti-tumour activity.

A synthetic approach to analogues of the terpenoid natural product antheminone A is described which employs (-)-quinic acid as starting material. A key conjugate addition step proved to be unpredictable regarding its stereochemical outcome however the route allowed access to two diastereoisomeric series of compounds. The results of biological assay of the toxicity of the target compounds towards non-small-cell lung cancer cell line A549 are reported.

Effect of Biopsychosocial Factors on Glycemic Control in Type 2 Diabetes Mellitus.

OBJECTIVE: To investigate the effect of diabetic patients' biopsychosocial factors on type 2 diabetes mellitus (T2DM) outcomes to contribute to diabetes mellitus management. STUDY DESIGN: Cross-sectional descriptive study. Place and Duration of the Study: Department of Family Medicine, School of Medicine, Firat University, Turkey, from October 2021 to March 2022. METHODOLOGY: A total of 210 type 2 diabetic patients were included. The sociodemographic form, Beck depression inventory (BDI), multidimensional perceived social support scale (MSPSS), general self-efficacy scale (GES), and Diabetes self-care activities scale (DSCA) were used to assess the biopsychosocial factors. Controlled diabetes and uncontrolled diabetes classification was made according to HbA1c level (HbA1c cut-off value: ≤7%). RESULTS: The median duration of T2DM (p=0.001), total cholesterol level (p=0.004) and fasting plasma glucose (p<0.001) were found to be higher in the uncontrolled diabetes group than in the controlled diabetes group. Spearman correlation test results showed a significant negative relationship between the scores of Beck depression and total cholesterol (r= -0.157, p = 0.023). There is a significant positive correlation between social support and total cholesterol (r=0.343, p<0.001), LDL (r=0.149, p= 0.031), triglyceride (r=0.165, p = 0.017), DSCA general diet score (r=0.367, p<0.001), DSCA physical activities (r=0.221, p = 0.001), DSCA glucose monitoring (r=0.302, p<0.001), DSCA foot care (r=0.311, p<0.001), and DSCA total scores (r=0.401, p<0.001). CONCLUSION: The present study showed that high BDI score was associated with low diabetes self-care score and presence of complications. Individuals' self-efficacy and high perception of social support were associated with increased diabetic self-care scores. KEY WORDS: Social support, Perception, Self care, Diabetes mellitus type 2, Diabetes complications, Depression.

Healthy life behaviors and suicide probability in university students.

This study aims to determine the sociodemographic factors and healthy life behaviors affecting suicide and suicide probability of university students. The research was designed as a complementary study and conducted with 334 students from several faculties and colleges at Ege University, Turkey. The study findings indicated that suicide probability could be affected by the students' age, their problems at school, their troubled relations with friends, and a psychiatric disorder history within the last year. Moreover, it was concluded that the students with healthy life behaviors had significantly lower scores on the Suicide Probability Scale and its subscales.

Thymoquinone alleviates doxorubicin induced acute kidney injury by decreasing endoplasmic reticulum stress, inflammation and apoptosis.

Doxorubicin (DOX) is used as an anticancer drug despite its many side effects. Thymoquinone (THQ) is a plant-derived substance that exhibits antioxidant and anti-inflammatory properties. We investigated the protective effects of THQ on DOX induced nephrotoxicity in rats. Rats were divided into five groups of eight: group 1, untreated control; group 2, olive oil group given olive oil intraperitoneally (i.p.) for 14 days; group 3, THQ group given 10 mg/kg THQ i.p. for 14 days; group 4, DOX group given a single dose of 15 mg/kg DOX i.p. on day 7 of experiment; group 5, DOX + THQ given 10 mg/kg THQ i.p. for 14 days and 15 mg/kg DOX i.p. on day 7. Kidney tissues were evaluated for histopathology. Caspase-3, IL-17, GRP78 and TNF-α immunostaining was used to determine the expression levels of these proteins among the groups. The TUNEL method was used to determine the apoptotic index. Total antioxidant status (TAS), total oxidant status (TOS), and TNF-α and TGF-ß1 levels in kidney tissue were measured using ELISA assay. Histopathologic damage, caspase-3, IL-17, GRP78 and TNF-α immunoreactivity, TUNEL positive cells, TOS, TNF-α and TGF-ß1 levels were increased in group 4 compared to group 1. The TAS of group 4 decreased compared to group 1. We found decreased caspase-3, IL-17, GRP78 and TNF-α expressions and TUNEL positive cells in group 5 compared to group 4. In rats given DOX, THQ reduced kidney damage by suppressing endoplasmic reticulum stress, inflammation and apoptosis pathways.

Vitamin B12 suppresses GADD153, prevents apoptosis and regulates the testicular function in methotrexate treated rat testis.

Methotrexate (MTX) is an anti-neoplastic drug that also causes testicular damage. Vitamin B12 (Vit B12) is a water soluble vitamin that is required for normal metabolism. We investigated Vit B12 as a possible protective agent against testicular damage caused by MTX treatment. We divided rats into four groups: control group, Vit B12 group treated with Vit B12 daily for 15 days, MTX group treated with MTX on day 8, MTX + Vit B12 group treated with MTX on day 8 + Vit B12 for 15 days. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone were measured. We also measured proliferating cell nuclear antigen (PCNA), connexin43 (Cx43) and the growth arrest- and DNA damage-inducible gene, 153 (GADD153), using immunohistochemical staining. Apoptosis was assessed using TUNEL staining. The MTX group exhibited degeneration of seminiferous tubules; decreased serum testosterone, LH and FSH levels; fewer PCNA positive cells; increased Cx43 expression; and increased GADD153 and TUNEL stained cells compared to the control group. These pathologic findings were substantially reversed In the MTX + Vit B12 group. MTX caused increased endoplasmic reticulum stress and apoptosis via GADD153. Consequently, Vit B12 potentially is a protective agent against damage caused by MTX.

Therapeutic effects of thymoquinone in doxorubicin-induced hepatotoxicity via oxidative stress, inflammation and apoptosis.

Cancer is a lethal disease that is characterized by uncontrolled cell division and proliferation, and it results in death in many organisms. Doxorubicin (DOX) is a therapeutic agent used for treatment of many cancer types, but it induces serious hepatotoxicity. In this study, we aimed to determine possible hepato-therapeutic effects of thymoquinone (THQ) on DOX-induced hepatotoxicity in rats. Rats were divided into five groups (n = 8): Control, THQ (10 mg/kg/day/i.p for 14 days), Olive Oil (equal volume with THQ for 14 days), DOX (single dose, 15 mg/kg/i.p on 7th day) and DOX + THQ (10 mg/kg/day/i.p and DOX 15 mg/kg/i.p on 7th day). At the end of the experiment, liver tissues were extracted and evaluated histopathologically. eNOS, iNOS and Cas-3 immunostaining were performed to determine the expression levels. TUNEL method was used to determine apoptotic index. Furthermore, liver tissue total antioxidant status (TAS), total oxidant status (TOS), TNF-α and TGF-ß levels were measured by ELISA assay. The DOX group showed histopathological deterioration compared to Control group. Moreover, apoptotic index, eNOS, iNOS and Cas-3 expressions increased in DOX group. While TAS level of the DOX group decreased, TOS level increased. TNF-α and TGF-ß levels increased in DOX group. However, there was improvement in DOX + THQ group compared to DOX group. Moreover, apoptotic cell number, eNOS, iNOS and Cas-3 expressions decreased in DOX + THQ group compared to DOX group. We concluded that thymoquinone can be used as a phytotherapeutic for reducing DOX-induced liver damage.

European Consumers' Willingness to Pay for Red Meat Labelling Attributes.

Food consumption in Europe is changing. Red meat consumption has been steadily decreasing in the past decades. The rising interest of consumers for healthier and more sustainable meat products provides red meat producers with the opportunity to differentiate their offers by ecolabels, origin and health claims. This international study analyses the European consumer preferences for red meat (beef, lamb and goat) in seven countries: Finland, France, Greece, Italy, Spain, Turkey and the United Kingdom. Through a choice experiment, 2900 responses were collected. Mixed multinomial logit models were estimated to identify heterogeneous preferences among consumers at the country level. The results indicate substantial differences between the most relevant attributes for the average consumer, as well as their willingness to pay for them in each country. Nevertheless, national origin and organic labels were highly valued in most countries.

Effects of vitamin B12 on methotrexate hepatotoxicity: evaluation of receptor-interacting protein (RIP) kinase.

In the study, we aimed to show the effects of vitamin B12 on the necrosis caused by methotrexate (MTX), a folic acid antagonist. Thirty-two rats were randomly assigned to four groups of eight rats per group. Control (n = 8), Vit B12 (n = 8) 3 µg/kg/ip B12 (15 days) per day throughout the experiment, MTX (n = 8) injected with a single dose of 20 mg/kg/ip MTX on 8th day of experiment, MTX + Vit B12 (n = 8) injected with a single dose of 20 mg/kg ip methotrexate on 8th day of experiment + 3 µg/kg/ip Vit B12 (15 days) per day throughout the experiment. Oxidant (TOS)/antioxidant (TAS) system, TNF-α and TGF-ß levels, AST and ALT, serum vitamin B12 levels were determined in the tissue. Cyclooxygenase-2 (Cox-2), receptor-interacting protein kinase 1 (RIP1) and 3 (RIP3) immunohistochemistry were applied to the liver tissue. TOS increased; TAS decreased; TNF-α and TGF-ß levels increased; AST and ALT levels changed after MTX hepatotoxicity. Vit B12 decreased significantly. COX-2, RIP1, and RIP3 immunoreactivity increased. Vit B12 showed improvement in all of the negative results. Vit B12 is an important supplement to be used against necrosis in tissue after MTX hepatotoxicity.

Motivations and Barriers for Sheep and Goat Meat Consumption in Europe: A Means-End Chain Study.

This international study involving seven European countries (Italy, UK, Finland, France, Spain, Greece, Turkey) was conducted to explore the relevant reasons that affect both consumer and non-consumer perceptions of sheep and goat meat. Laddering and means-end chain theory were applied. The results indicate that consumers associate sheep and goat meat with a unique taste, authenticity and natural production, linked with values such as health and enjoyment of life. In contrast, non-consumers mainly feel disgusted when they think and feel about these meats, and do not associate any specific health benefits to their consumption, disliking their taste, odour and fat content. This study is based on qualitative research. Only analytical generalizations are possible, expanding the theory on what drives consumer behaviour when purchasing meat. No previous means-end chain studies are available in the literature regarding small ruminants' meat consumer preferences.

Performance of acidified 14C-urea capsule breath test during pantoprazole and ranitidine treatment.

BACKGROUND AND AIM: Urea breath test (UBT) results could be false negative in patients taking antisecretory drugs. This effect would be prevented by citric acid administration during UBT. We prospectively investigated whether acidified 14C-urea capsule prevents false negative UBT results in patients taking antisecretory drugs and show interference with the duration of medications. METHODS: Sixty Helicobacter pylori positive patients were included. Pantoprazole (40 mg/day) was given to 27 patients for 28 days and ranitidine (300 mg. o.d.) to 33 patients for 60 days. Urea breath tests were repeated on days 14 and 28 in both groups and on day 60 in the ranitidine group. RESULTS: The baseline mean breath counts of two groups did not show any significant difference. Pantoprazole led to a significant decrease in mean breath counts on day 14 (P < 0.005). Six of 27 and 3 of 25 patients taking pantoprazole developed negative or equivocal UBT results on days 14 and 28, respectively. Two of 32, 2 of 32 and 3 of 21 patients taking ranitidine developed negative or equivocal UBT results on days 14, 28 and 60, respectively. CONCLUSIONS: The use of acidified 14C-urea capsule did not prevent false negative UBT results in patients taking pantoprazole and ranitidine, and the duration of medication does not affect the test results.

Papular elastorrhexis: clinical perspectives.

First described by Bordas in 1987, papular elastorrhexis (PE) is a rare elastic fiber disorder of the skin characterized by multiple, discrete, asymptomatic, firm, nonfollicular, monomorphous, 1-5 mm, circumscribed, hypopigmented, oval to round papules, symmetrically distributed on the chest, abdomen, back, shoulders, arms, and thighs. The onset of the condition is usually in the first or second decade of life. PE appears to be an exceedingly rare entity, with 33 cases reported in the literature until now. However, the disorder might be underestimated probably because of its subtlety, asymptomatic course, and benign nature of clinical alterations, which can easily be confused with other dermatoses such as acne scars. Clinical and histopathological differential diagnosis of PE is broad and includes papular acne scars, eruptive collagenoma, disseminated lenticular dermatofibrosis (as a component of Buschke-Ollendorff syndrome), white fibrous papulosis of the neck, pseudoxanthoma elasticum, pseudoxanthoma elasticum-like papillary dermal elastolysis, middermal elastolysis, and perifollicular elastolysis. Treatment of PE is a matter of debate and no reliable curative option exists.

A Comparison of Iterative Reconstruction and Prone Imaging in Reducing the Inferior Wall Attenuation in Tc-99m Sestamibi Myocardial Perfusion SPECT.

OBJECTIVE: Prone positioning, iterative reconstruction (IR-OSEM) and electrocardiography (ECG) gating have been demonstrated to improve the specificity of myocardial perfusion SPECT (MPS) in the diagnosis of coronary artery disease. METHODS: The gated supine and prone MPS images of 45 patients were reconstructed with both IR-OSEM [supine (SIR) and prone (PIR)] FBPs [supine (SFBP), prone (PFBP)] for comparison. Perfusion, wall motion (WM) and wall thickening were also interpreted semi-quantitatively. Two groups were generated as those with normal or abnormal findings. Segmental myocardial tracer uptake values were noted from four of the reconstructed images from 17 segment model of bullseye. RESULTS: The difference between mean values and the standard deviations of the % tracer uptakes of inferior wall segments were statistically significant in all images. The normalcy rates were highest in PIR images, followed by PFBP and SIR images. The number of patients with any perfusion abnormality were 42, 12, 32, and 6, in SFBP, PFBP, SIR and PIR images, respectively. The six patients with perfusion abnormality in PIR images were re-evaluated with rest images and were diagnosed with a fixed perfusion defect. There was positive correlation between WM and either PFBP or PIR images. Sixteen patients' WM were evaluated as abnormal while only 6 patients' perfusions were abnormal in PIR. CONCLUSION: Prone imaging in addition to a supine perfusion SPECT improves imaging quality of the inferior wall, especially when reconstructed with iterative methods. If prone imaging can not be performed, ECG-gating can also be used as a beneficial method.

Does size matter? Retrospective analysis of large gynecologic tumors.

OBJECTIVE: To evaluate the characteristics of patients who underwent surgery due to the presence of a large pelvic-abdominal mass over a 5-year period in a university clinic. MATERIAL AND METHODS: Among 3476 gynecologic operations, intraoperative findings were evaluated retrospectively. Uterine and/or adnexal masses smaller than 20 cm were excluded to refine "large" tumors and 74 patients with large tumors were enrolled in the study group. Demographic characteristics, intraoperative findings, and results of histopathologic examinations were recorded. Moreover, preoperative and intraoperative findings were compared among tumors with adnexal origin according to their final histopathologic results. RESULTS: The mean age of the patients was 46 years. The most common symptom was abdominal pain, as recorded in 38 (51.4%) patients. Among all patients, 31 (41.9%) had coexisting illness and 13 (17.6%) had a history of surgery. The mean tumor diameter was 25.9±8.6 cm (20-60) and 60 (78.9%) tumors were of adnexal origin. The ratios of malignancy for large adnexal and uterine tumors were 34.4% and 12.5%, respectively. When the large adnexal tumors were re-evaluated, the mean cancer antigen (CA) 125 level was significantly higher, and ascites was more frequently detected in malignant tumors (p<0.01) then in benign and borderline tumors. CONCLUSION: Benign and borderline tumors are more common among large abdominopelvic masses, although the presence of ascites and elevated CA 125 may present malignancy in large gynecologic tumors. Further studies with larger sample sizes are needed to define the characteristics of large tumors and their malignant potentials.

Media Use by Children, and Parents' Views on Children's Media Usage.

BACKGROUND: New (mobile phones, smartphones, tablets, and social media) and traditional media (television) have come to dominate the lives of many children and adolescents. Despite all of this media time and new technology, many parents seem to have few rules regarding the use of media by their children and adolescents. OBJECTIVES: The aim of this study was to evaluate media access/use of children and to evaluate beliefs and attitudes of parents concerning the use of old and new media in Turkey. METHODS: This is a cross-sectional electronic survey of a national convenience sample in Turkey via SurveyMonkey, including 41 questions regarding topics relevant to television, computers, mobile phones, iPad/tablet use, and social media accounts. RESULTS: The responses of the 333 participants (238 women, 95 men; 27-63 years) were evaluated. The average daily watching alone time was 0 to 2 hours among 53.4% (46/86), and daily coviewing time with parents of children was 0 to 2 hours among 62.7% (54/86) of children below 2 years of age. Regarding parents' monitoring their children's computer use (n=178), 35.4% (63/178) of the parents prefer coviewing, 13.5% of the parents use a family filter (24/178), and 33.1% (59/178) of the parents prefer to check Web history. Approximately 71.2% (237/333) of the participants had an iPad/tablet in the house, 84.3% (200/333) of the parents give their children permission to use the iPad/tablet. Of the parents, 22.5% (45/200) noted that their children used the iPad/tablet at the table during lunch/dinner and 57.9% (26/45) of these children were aged 5 years and below. Of parents, 27.3% (91/333) agreed that the optimal age for owning a mobile phone was 12 years, and 18.0% (60/333) of the parents noted that their children (one-third was below 2 years) used the mobile phone at the table during meals. A total of 33.3% (111/333) children/adolescents have a Facebook profile, and 54.0% (60/111) were below 13 years of age. Approximately 89.2% (297/333) of the parents emphasized that the Internet is essential for their child's education. DISCUSSION: According to our study results, knowledge regarding the use of old and new media is limited among the parents in Turkey. Our study showed that screen time and mobile device use (including during meals) are common in children below 2 years of age, whereas no screen time was recommended for children below 2 years of age. We concluded that there is need for evidence-based guidelines regarding the use of the Internet and social media for parents and parents should ensure that there is a plan in place for the use of children's media.

The effects of rapamycin and 3-methyladenine on nitric oxide synthase enzymes in cisplatin-induced neurotoxicity / Efectos de la rapamicina y la 3-metiladenina sobre la enzima óxido nítrico sintasa en la neurotoxicidad inducida por cisplatino

SUMMARY: The aim of this study was to determine the relationship of autophagy-enhancing rapamycin (RAPA) and autophagy- inhibitor 3-methyladenine (3-MA) with Nitric oxide synthases (NOS) in Cisplatin (CIS)-induced neurotoxicity in rats. Rats were divided into 4 groups (n=10): Control was applied saline, CIS (a single dose of 8mg/kg intraperitoneal (i.p.) on 7th day of experiment), RAPA+CIS (2 mg/kg/i.p. RAPA per day and 8 mg/kg/i.p. CIS on 7th day), 3-MA+CIS (15 mg/kg/i.p. 3-MA per day and 8 mg/kg/i.p. CIS on 7th day). Rats were sacrificed under anesthesia. Brain tissues were evaluated histopathologically. eNOS, Inos, nNOS and MAP 2 immunostaining were performed to determine the expression levels of these proteins among groups. Superoxide dismutase (SOD), Catalase (CAT), Malondialdehyde (MDA) and Interleukin IL-6 levels in brain tissue and serum nitric oxide (NO) level were measured by ELISA assay. In histopathological evaluation, neurodegeneration was seen in the CIS group. There was an increase in eNOS, iNOS and nNOS immunostaining in CIS group. While MAP2 immunostaining of the CIS group decreased. There was a decrease in SOD and CAT levels of brain tissue in CIS group. However, there was an increase in MDA, IL-6 and NO levels of brain tissue in CIS group. We found that antioxidant capacity increase while, inflammation and nitric oxide levels decreased in the RAPA-treated group. 3-MA does not have a significant effect. We suggest that CIS-induced neurotoxicity is more effective than Rapa 3-MA and may also be linked to NOS enzymes.

RESUMEN: El objetivo de este estudio fue determinar la relación de la rapamicina potenciadora de la autofagia (RAPA) y el inhibidor de la autofagia 3-metiladenina (3-MA) con óxido nítrico sintasas (NOS) en la neurotoxicidad inducida por cisplatino (CIS) en ratas. Las ratas se dividieron en 4 grupos (n = 10): grupo control se aplicó solución salina, CIS (una dosis única de 8 mg / kg intraperitoneal (ip) el día 7 del experimento), RAPA + CIS (2 mg / kg / ipRAPA por día y 8 mg / kg / ip CIS el día 7), 3-MA + CIS (15 mg / kg / ip 3-MA por día y 8 mg / kg / ip CIS el día 7). Las ratas se sacrificaron bajo anestesia y los tejidos cerebrales fueron analizados histopatológicamente. Se realizaron inmunotinciones con eNOS, Inos, nNOS y MAP 2 para determinar los niveles de expre- sión de estas proteínas entre los grupos. Se midieron los niveles de superóxido dismutasa (SOD), catalasa (CAT), malondialdehído (MDA) e interleucina IL-6 en el tejido cerebral y el nivel de óxido nítrico (NO) en suero mediante ensayo ELISA. En la evaluación histopatológica, se observó neurodegeneración en el grupo CIS. Hubo un aumento en la inmunotinción de eNOS, iNOS y nNOS en el grupo CIS. Mientras que la inmunotinción de MAP2 del grupo CIS disminuyó. Hubo una disminución en los niveles de SOD y CAT del tejido cerebral en el grupo CIS, sin embargo, hubo un aumento en los niveles de MDA, IL-6 y NO en el tejido cerebral en el grupo CIS. Observamos que la capacidad antioxidante aumentó, mientras que la inflamación y los niveles de óxido nítrico disminuyeron en el grupo tratado con RAPA. 3-MA no tiene un efecto significativo. Sugerimos que la neurotoxicidad inducida por CIS es más eficaz que Rapa 3-MA y también puede estar relacio- nada con las enzimas NOS.

Chloroquine ameliorates adriamycin-induced testicular damage by suppressing the inflammation and apoptosis in rats: a histological, immunohistochemical and biochemical study / La cloroquina mejora el daño testicular inducido por la adriamicina al suprimir la inflamación y la apoptosis en ratas: un estudio histológico, inmunohistoquímico y bioquímico

SUMMARY: Adriamycin (ADR) is an anthracycline antibiotic used for treatment of many types of cancer. However, its applications may damage to healthy tissues. Chloroquine (CLQ) is an anti-inflammatory agent used in treatment of many inflammation associated diseases such as malaria and rheumatoid arthritis. Moreover, it is used in the treatment of pneumonia caused by COVID-19. The aim of this study is to determine possible therapeutic effects of Chloroquine on Adriamycin-induced testicular toxicity in rats. We investigated the effect of CLQ on testicular injury caused by ADR. Rats were divided into four groups: Control, ADR, CLQ, ADR+CLQ. After administrations, animals were sacrificed, and testis tissues were extracted from the animals for the further examinations. Histopathological changes in testis tissues were evaluated and TNF-α and IL-6 immunostaining were performed to determine the expression levels of these cytokines. TUNEL method were used for evaluation of apoptotic index. Moreover, serum testosterone levels were measured by ELISA assay. We observed that ADR group showed histopathological deterioration when compared to the Control group and CLQ treatment ameliorated this damage induced by Adriamycin.An increase in TNF-α and IL-6 immunoreactivities and in the number of apoptotic cells and a decrease in serum testosterone levels were determined in the ADR group compared to the Control and CLQ group. Furthermore, our examinations showed an improvement in testicular tissue in ADR+CLQ group in terms of these parameters when compared to the ADR group. We suggest that CLQ can be used as a protective agent to reduce the toxic effects of Adriamycin as a result of its anti-inflammatory and anti-apoptotic properties.

RESUMEN: La adriamicina (ADR) es un antibiótico de antraciclina que se usa para el tratamiento de muchos tipos de cáncer. Sin embargo, sus aplicaciones pueden dañar los tejidos sanos. La cloroquina (CLQ) es un agente antiinflamatorio que se utiliza en el tratamiento de enfermedades asociadas a la inflamación, tal como la malaria y la artritis reumatoide. También se utiliza en el tratamiento de la neumonía causada por COVID-19. El objetivo de este estudio fue determinar los posibles efectos terapéuticos de la cloroquina sobre la toxicidad testicular inducida por adriamicina en ratas. Investigamos el efecto de CLQ sobre la lesión testicular causada por ADR. Las ratas se dividieron en cuatro grupos: Control, ADR, CLQ, ADR + CLQ. Después de las administraciones, se sacrificaron los animales y se extrajeron los testículos de los animales para los exámenes adicionales. Se evaluaron los cambios histopatológicos en los tejidos testiculares y se realizó la inmunotinción de TNF-α e IL-6 para determinar los niveles de expresión de estas citocinas. Se utilizó el método TUNEL para la evaluación del índice apoptótico. Además, los niveles de testosterona en suero se midieron mediante un ensayo ELISA. El grupo ADR mostró un deterioro histopatológico en comparación con el grupo Control y observamos que el tratamiento con CLQ mejoró el daño inducido por Adriamicina. Un aumento en las inmunorreactividades de TNF-α e IL-6 y en el número de células apoptóticas además de una disminución en los niveles séricos de testosterona se determinaron en el grupo de ADR en comparación con el grupo de control y CLQ. Además, nuestros exámenes mostraron una mejora en el tejido testicular en el grupo ADR + CLQ en términos de estos parámetros en comparación con el grupo ADR. Sugerimos que CLQ se puede utilizar como agente protector para reducir los efectos tóxicos de la Adriamicina, gracias a sus propiedades antiinflamatorias y antiapoptóticas.

The effects of tangential radiotherapy on lung clearance in breast cancer patients.

PURPOSE: The aim of this study was to investigate the effects of tangential radiotherapy (RT) on lung clearance in the patients with breast cancer by using (99m)Tc-DTPA aerosol scintigraphy. MATERIAL AND METHODS: Thirty-three female patients [non-smoker: 20, ex-smoker: 13] performed surgery and systemic chemotherapy for breast carcinoma [47+/-13 years] were included in the study. All patients underwent (99m)Tc-DTPA aerosol scintigraphy prior to RT (pre RT), midway through RT (mid RT) and after RT (post RT). Total dose was 50 Gy in modified radical mastectomy and 60 Gy in lumpectomy (2 Gy/fraction). Posterior dynamic images of lungs were obtained immediately after the inhalation of (99m)Tc-DTPA aerosol. RESULTS: Pulmonary function tests were normal in three measurements for all cases. In the ex-smokers, there was no significant difference among pre RT, mid RT and post RT clearance values in both lungs. Pre RT lung clearance in non-smoker group did not differ from that in ex-smokers. However, the lung clearance for non-smoker group showed significantly increase following RT. CONCLUSION: In this study, we observed that tangential radiotherapy caused an increase in the lung clearance in the cases of non-smokers even in non-irradiated lung, and that the effect of RT on lung clearance was closely depended on smoking habit before RT.