The efficacy of HDDPiW-jSB solution on docetaxel-induced alopecia of rats.

OBJECTIVE: Chemotherapy induced alopecia (CIA) is one of the most common side effects in cancer patients, however; it doesn't have an effective pharmacological treatment yet. In this study we aimed to research the protective effect of newly developed HDDPiW-jSB solution on docetaxel (DTX) -induced rat alopecia model. MATERIAL AND METHODS: Docetaxel (10 mg/kg/week) was administered to the 6-8 months old rats for three weeks. HDDPiW-jSB solution was applied once or twice a week for 4 weeks beginning prior to one week before DTX. Rat hair follicles were evaluated with hematoxylin-eosin and immune-histochemical staining. RESULTS: In the first stage of this study, alopecia was successfully developed by DTX (10 mg/kg/three times) application. In the second stage of the study, application of HDDPiW-jSB solution, did not change the study parameters significantly on control group. The solution improved the anagen hair follicle count and Bcl-2 levels in the skin samples of DTX-induced alopecic rat groups, especially when applied twice weekly. Additionally, level of Caspase 3 was decreased. HDDPiW-jSB solution was safe when applied on the skin. CONCLUSION: Topical HDDPiW-jSB solution could be effective and safe for the protection of DTX-induced alopecia in rat models.

The European NUTS-level election dataset: A tool to map European electoral geography.

Datasets on subnational election results in Europe frequently do not match with regional statistics available for cross-national research, mainly because territorial statistical units change over time and do not map onto the national electoral districts. This hinders consistent comparative research across time. This research note introduces EU-NED, a new dataset on subnational election data that covers national and European parliamentary elections for European countries over the past 30 years. EU-NED's major contribution is that it provides election results on disaggregated levels of the statistical territorial units used by Eurostat with an unprecedented consistency and temporospatial scope. Moreover, EU-NED is integrated with the Party Facts platform, allowing for a seamless integration of party-level data. Using EU-NED, we present first descriptive evidence on the European electoral geography and suggest avenues of how EU-NED can facilitate future comparative political science research in Europe.

The role of hepatic and renal functions in the development of retinopathy of prematurity: Is proteinuria a new risk factor?

PURPOSE: To investigate the association of hepatic and renal parameters with the development of retinopathy of prematurity (ROP) in premature infants with a gestational age ≤ 32 weeks. METHODS: Medical records of 240 preterm infants were reviewed retrospectively, 85 of them were grouped as type 1, type 2 ROP, and control group. The 4th week hepatic and renal function test results of the groups, on the day of their first ROP examinations, were compared for the risk of development of ROP and the development of type 1 ROP. RESULTS: In this study, 12, 35, and 38 infants were enrolled in the type 1, type 2 ROP, and control group, respectively. The average gestational age and birth weight were higher; however, the duration of oxygen treatment was lower in the control group (p < 0.001). The blood glucose level was significantly higher in the type 1 ROP group than in the other groups (p = 0.023). The mean of total serum bilirubin of the type 1 ROP group was significantly lower than those of the type 2 ROP and control group (p = 0.032). Proteinuria was present in 85.7% of preterms with treatment-requiring ROP and proteinuria increased the risk of ROP by 3.9 times (OR with 95% CI 3.9 (1.19-12.75), p = 0.042). CONCLUSION: We found significantly higher blood glucose and lower total bilirubin level in the type 1 ROP group. Moreover, our findings suggest that proteinuria may not be only a comorbidity factor but also related to a higher frequency of ROP and type 1 ROP in preterm infants.

Empathy-based counterspeech can reduce racist hate speech in a social media field experiment.

Despite heightened awareness of the detrimental impact of hate speech on social media platforms on affected communities and public discourse, there is little consensus on approaches to mitigate it. While content moderation-either by governments or social media companies-can curb online hostility, such policies may suppress valuable as well as illicit speech and might disperse rather than reduce hate speech. As an alternative strategy, an increasing number of international and nongovernmental organizations (I/NGOs) are employing counterspeech to confront and reduce online hate speech. Despite their growing popularity, there is scant experimental evidence on the effectiveness and design of counterspeech strategies (in the public domain). Modeling our interventions on current I/NGO practice, we randomly assign English-speaking Twitter users who have sent messages containing xenophobic (or racist) hate speech to one of three counterspeech strategies-empathy, warning of consequences, and humor-or a control group. Our intention-to-treat analysis of 1,350 Twitter users shows that empathy-based counterspeech messages can increase the retrospective deletion of xenophobic hate speech by 0.2 SD and reduce the prospective creation of xenophobic hate speech over a 4-wk follow-up period by 0.1 SD. We find, however, no consistent effects for strategies using humor or warning of consequences. Together, these results advance our understanding of the central role of empathy in reducing exclusionary behavior and inform the design of future counterspeech interventions.

An assessment of the protective effect of gonadotropin-releasing hormone agonist and antagonist on bleomycin-induced ovarian toxicity in rats.

The aim of this study is to evaluate the effect of GnRH agonist or GnRH antagonist therapy on bleomycin-administered rats by examining ovarian follicle counts and AMH levels. A total of 30 female Wistar albino rats aged 4-6 months were randomly divided into 4 groups. First, an intramuscular injection of bleomycin (30 mg/m2) was administered to all except the control group on the 1st, 8th and 15th days. The control group (Group I) was administered 0.1 mL intramuscular saline on those days. The bleomycin group (Group II) was followed up without any further treatment. The bleomycin + GnRH agonist group (Group III) was administered subcutaneous GnRH agonist triptorelin (1 mg/kg) at the same time as the bleomycin injections. The bleomycin + GnRH antagonist group (Group IV) was administered 1 mg/kg cetrorelix acetate subcutaneously, concurrently with the bleomycin. Although AMH levels were lower in the bleomycin group than in all the other groups, there was no statistically significant difference between the groups in terms of AMH levels (p > .05). In the bleomycin + cetrorelix acetate and bleomycin + triptorelin groups, significantly higher primordial, secondary and tertiary follicle counts were determined compared to the bleomycin group (p < .001). In conclusion the harmful effects of bleomycin on ovarian reserve can be reduced by the simultaneous administration of GnRH agonist or GnRH antagonist.

Can Complete Blood Count Parameters Predict Retinopathy of Prematurity?

Objectives: To predict the risk of retinopathy of prematurity (ROP) development according to routine complete blood count (CBC) parameters. Materials and Methods: The medical records and CBC results of 150 premature neonates were retrospectively evaluated. As ROP develops 1 month after birth, first month CBC profiles of neonates without ROP (non-ROP), with ROP (ROP group), and those with Type 1, Type 2, and Stage 1+2 ROP were compared. Besides known statistical methods like Student's t-test, logistic regression and classification & regression tree (C&RT) analysis were also done to identify a reliable quantitative predictive parameter. Results: Mean gestational age and birth weight of the ROP group (n=99) and non-ROP (n=43) group were 29.39±3.43 and 32.05±2.20 weeks and 1382.44±545.30 and 1691.51±360.84 grams, respectively (p<0.001, p<0.001). Average hemoglobin (Hb) (p<0.001), hematocrit (HCT) (p<0.001), erythrocyte (p=0.005), mean corpuscular hemoglobin (MCH) (p=0.020), and MCH concentration (p=0.019) values of the ROP group were lower than those of the non-ROP group. Leukocyte was higher in the ROP group (p=0.018). Hb [odds ratio (OR)=0.668, 95% confidence interval (CI)=0.555-0.804, p<0.001], red cell distribution width (RDW) (OR=1.282, 95% CI=1.012-1.624, p=0.040), leukocyte (OR=1.157, 95% CI=1.053-1.271, p=0.002), and platelet (OR=0.997, 95% CI: 0.994-0.999, p=0.036) values differed significantly between the two groups. Platelet, MCV, and MCH parameters were found to be lower in the Type 1 ROP group compared to the Stage 1+2 ROP group (p<0.005). MCH was the most prominent predictor (cut-off: 34.43 pg) according to the results of C&RT analysis. Conclusion: As Hb plays an important role in oxygen transport, low levels of Hb and especially MCH may cause increased vascular endothelial growth factor secretion from the hypoxic retina, thereby causing ROP. Therefore, the results of this study are encouraging regarding the use of the abovementioned CBC parameters as a simple screening test to predict ROP.

The Effects of Hyaluronic Acid on Traumatic Urethral Inflammation.

PURPOSE: This study investigated the possible beneficial effect of hyaluronic acid (HA) on traumatic urethral healing. METHODS: A total of 40 adult male Wistar rats were randomized into four groups: control, sham (serum physiologic; SF group), HA 1.8%, and HA 3%. A tiny hook was introduced and drawn at the 12 o'clock position into the urethra for the SF and HA groups to create a urethral inflammation model. Either SF or HA was applied intraurethrally for 5 consecutive days. After a 15-day follow-up period (21st day of the study), penile tissue was harvested and evaluated histopathologically. RESULTS: None of the groups showed inflammation at the end of study. Pathological findings such as calcification, hemorrhage, and stenosis were observed in the wound healing and these findings were present in all trauma groups. A significant increase in tissue thickness was observed in the group treated with saline (p = 0.004). No statistically significant difference was found in the two groups receiving HA treatment compared to the SF group. CONCLUSION: These data suggest that HA does not provide a beneficial effect on the connective tissue repairment when it is applied locally during the acute period of urethral injury for 5 consecutive days. There is a need for further studies in which the duration of drug use is extended or the dosage is increased.

Evaluation of oxaliplatin-induced pulmonary toxicity in rats.

INTRODUCTION: The mechanism of oxaliplatin (OXA) induced pulmonary toxicity is not fully understood. AIM OF THE STUDY: The present study was designed to investigate the pulmonary toxicity of OXA that has been reported in previous studies. Study design: animal experiments. MATERIAL AND METHODS: A total of 40 female Wistar rats were divided into 5 groups. In group 1, 5% glucose was injected intra-peritoneally; then the rats were sacrificed on day 14. OXA was administered in groups 2, 3, 4, and 5; then the animals were sacrificed on day 7 in group 2, day 14 in group 3, day 28 in group 4 and day 48 in group 5. The groups were further categorized as short-term administration and long-term administration groups. Furthermore, tissue glutathione peroxidase (GPX) activity was measured in all rats. RESULTS: The mean GPX activities were 0.66 U/mg in the sham group, 0.74 U/mg in the short-term groups, and 0.74 U/mg in the long-term groups. We found that long-term OXA administration causes pulmonary toxicity resulting in increased intra-alveolar/interstitial macrophages and interstitial pneumonia. Similarly, we found reduced and permanent tissue GPX activity in rats that received OXA in higher doses and for a long term. CONCLUSIONS: Long-term OXA therapy causes toxic changes in the lung tissue.

Detrimental effect of Hypericum perforatum on ovarian functions

Objective: Hypericum perforatum is widely used for depression and distress treatment as an over-the-counter plant at any age. This study investigated the safety of H. perforatum on ovarian function and infertility. Material and Methods: H. perforatum was given to rats in two different dosages (100 and 300 mg/kg/day) with drinking water for four weeks. Half of the treatment groups were sacrificed at the end of the four-week intervention, the remainder was sacrificed after an additional four-week waiting period to see if there was reversibility. At the end of the experiment, blood samples and both ovarian tissues were obtained under anesthesia with ketamine and xylazine (50 mg/kg and 5 mg/kg, respectively). Results: Although primordial follicle numbers were not affected with a dose of 100 mg/kg, they were significantly decreased (28.6%) when the dose was tripled. Primary follicle numbers stayed the same, but secondary and tertiary follicles numbers were significantly dose-dependently decreased, and remained significantly low four weeks after the intervention. Anti-mullerian hormone (AMH) levels were not significantly different between the groups. Conclusion: H. perforatum treatment did not change serum levels of AMH because the primary follicle number did not decrease. However, the other follicle counts decreased in a dose-dependent manner and full recovery was not regained after four weeks. The detrimental effect of H. perforatum on primordial follicles should be taken into consideration because any woman using H. perforatum could also experience ovarian failure.

Effect of Ozone in Freund's Complete Adjuvant-Induced Arthritis.

OBJECTIVES: This study aims to investigate the effectiveness and reliability of ozone (O3) in Freund's complete adjuvant (FCA)-induced arthritis, an animal model for rheumatoid arthritis. PATIENTS AND METHODS: Thirty-six four- to five-month-old male Wistar rats weighing between 274-420 gr were used in this study. Saline was injected into the hind paws of half of these rats, and FCA was injected into the other half. At the end of two weeks, 40 µg of O3 was administered to nine rats from each group twice a week for seven total doses. The rats were followed-up in terms of clinical findings. At the sixth week, the rats were sacrificed and serum malondialdehyde, glutathione peroxidase, and superoxide dismutase levels were measured. In addition, ankle joints were separated for histopathological examination. RESULTS: Significant improvement was observed in terms of hind-paw diameter, severity of arthritis, and histopathological findings of inflammation after O3 treatment in the group with FCA-induced arthritis. Although it was not quite significant, an upward trend was detected in oxidative stress markers with O3 treatment. CONCLUSION: This study, the first to investigate the effects of systemic O3 on the clinical and histopathological outcomes of rheumatoid arthritis, indicates that O3 is a highly effective and reliable treatment method in FCA-induced arthritis in animal models.

Utilizing prestin as a predictive marker for the early detection of outer hair cell damage.

PURPOSE: To evaluate prestin as a biomarker for the identification of early ototoxicity. MATERIALS AND METHODS: Rats (n = 47) were randomly assigned to five groups: low-dose (LAG) or high-dose (HAG) amikacin (200 and 600 mg/kg/day, respectively, for 10 days), low-dose (LCIS)or high-dose (HCIS) cisplatin (single doses of 5 and 15 mg/kg, respectively, for 3 days), and control (n = 8). At the end of the experiment, measurement of distortion product-evoked otoacoustic emissions (DPOAE) were performed to evaluate hearing, then blood samples and both ear tissues were collected under anesthesia. Prestin levels were determined by ELISA. Cochlear damage was evaluated histologically using a 4-point scoring system. RESULTS: The mean serum prestin levels were 377.0 ±â€¯135.3, 411.3 ±â€¯73.1, 512.6 ±â€¯106.0, 455.0 ±â€¯74.2 and 555.3 ±â€¯47.9 pg/ml for control, LCIS, HCIS, LAG and HAG groups, respectively. There was significant difference between prestin levels of Control-LCIS-HCIS groups (p = 0.031) and prestin levels of Control-LAG-HAG groups (p = 0.003). There were also significant differences in prestin levels between the low- and high-dose cisplatin and amikacin groups (p = 0.028 and p = 0.011, respectively). Each group had significantly lower DPOAE results at 4, 6 and 8 kHz than control groups (p < 0.001). The LAG, HAG, LCIS and HCIS groups had significantly higher cochlear damage scores than the control group (p < 0.05). CONCLUSIONS: Higher doses of cisplatin and amikacin were associated with the greatest increases in serum prestin level and cochlear damage score. The results of this study suggest that prestin is a promising early indicator of cochlear damage.

Investigation of the embryotoxic and teratogenic effect of Hypericum perforatum in pregnant rats.

OBJECTIVE: Hypericum perforatum (HP) is a herbal product used in the treatment of depression, but its harm on the fetus has not been established. This study investigated the effects of HP according to fetal clinical, morphologic, and histologic findings. Study design is an animal study. MATERIALS AND METHODS: Fifty-four 4-5-month-old female Wistar rats were divided into three groups: control, 100 mg/kg HP, and 300 mg/kg HP. HP treatment using drinking water was started one week before mating and ended with the delivery of pups. RESULTS: HP exposure before conception diminished the pregnancy rate and decreased the fetal number; during pregnancy it tended to increase the duration of gestation, and deteriorated the fetal development as determined using body weight. It also damaged liver and kidney tissues, most probably due to oxidative stress, as supported through inducible nitric oxide synthase antibody staining findings at both doses. CONCLUSION: HP should not be recommended to women who would like to be pregnant or are pregnant because it can be harmful for both fetal and maternal health.

Effect of Pycnogenol® on an experimental rat model of allergic conjunctivitis.

BACKGROUND: Allergic conjunctivitis (AC) is a frequent and challenging disease in ophthalmology practice. Cell protective effect of Pycnogenol® (PYC) depends on its antioxidant and anti-inflammatory properties. The aim of the study is to investigate the effect of PYC on an experimental AC model. METHODS: Ovalbumin and Al(OH)3 were given seven times intraperitoneally (i.p.) every other day and ovalbumin installed everyday directly on conjunctiva to create an AC rat model. Then, PYC (3 or 10 mg/kg i.p.) was applied in the study groups. Control rats were given adjuvant Al(OH)3 i.p. and topical saline on conjunctiva. A negative control group in which only PYC (10 mg/kg/7 days) was administered i.p. and an AC positive control group which have been given dexamethasone (1 mg/kg/7 days) was created. Mast cells were counted with a microscope; histological evaluation was performed with H-E and toluidine blue, mast cell tryptase, and TNF-α and TGF-ß staining. RESULTS: Pycnogenol treatment alone did not show any detrimental effect. Mast cell count (MCC) decreased in both dexamethasone and 10 mg/kg given PYC treatment groups compared to positive control group and these results were statistically significant (MCC 1.85 ± 0.69, p < 0.001; 2.42 ± 0.53, p = 0.003). Negative staining with TGF-ß and weak focal staining with TNF-α were the common findings of dexamethasone and PYC treatment groups. CONCLUSIONS: The animal model of AC was successfully developed by using aforementioned way. PYC is a safe herbal product and it has alleviated the findings of ovalbumin-induced AC-similar to dexamethasone-histologically in this experimental model. These results are promising for the future of AC treatment.

Ophthalmic adverse effects of nasal decongestants on an experimental rat model.

PURPOSE: To investigate the potential effects of chronic exposure to a nasal decongestant and its excipients on ocular tissues using an experimental rat model. METHODS: Sixty adult male Wistar rats were randomized into six groups. The first two groups were control (serum physiologic) and Otrivine® groups. The remaining four groups received the Otrivine excipients xylometazoline, benzalkonium chloride, sorbitol, and ethylene diamine tetra acetic acid. Medications were applied into both nostrils twice a day for 8 weeks. Before the rats were sacrificed, epithelial staining, the Schirmer test, and intraocular pressure measurements were performed under ketamine/xylasine anesthesia (50 and 5 mg/kg, respectively). RESULTS: Epithelial defects and dry eye were common findings in all study groups. Cataracts developed in two cases clinically. Histopathological evaluation revealed many different pathological alterations in all parts of the ocular tissues such as corneal edema, polypoid proliferation and hyalinization of the vessel wall, cystic formation of the lens, retinal nerve fiber layer degeneration, and corpora amylacea formation of the lacrimal gland. CONCLUSIONS: Prolonged usage of the nasal decongestant xylometazoline and its excipients may cause ophthalmic problems such as dry eyes, corneal edema, cataracts, retinal nerve fiber layer, and vascular damage in rats. Although these results were obtained from experimental animals, ophthalmologists should keep in mind the potential ophthalmic adverse effects of this medicine and/or its excipients and exercise caution with drugs containing xylometazoline, ethylene diamine tetra acetic acid, benzalkonium chloride and sorbitol for patients with underlying ocular problems.

Ophthalmic adverse effects of nasal decongestants on an experimental rat model / Efeitos oftálmicos adversos de descongestionantes nasais em modelo experimental com ratos

ABSTRACT Purpose: To investigate the potential effects of chronic exposure to a nasal decongestant and its excipients on ocular tissues using an experimental rat model. Methods: Sixty adult male Wistar rats were randomized into six groups. The first two groups were control (serum physiologic) and Otrivine® groups. The remaining four groups received the Otrivine excipients xylometazoline, benzalkonium chloride, sorbitol, and ethylene diamine tetra acetic acid. Medications were applied into both nostrils twice a day for 8 weeks. Before the rats were sacrificed, epithelial staining, the Schirmer test, and intraocular pressure measurements were performed under ketamine/xylasine anesthesia (50 and 5 mg/kg, respectively). Results: Epithelial defects and dry eye were common findings in all study groups. Cataracts developed in two cases clinically. Histopathological evaluation revealed many different pathological alterations in all parts of the ocular tissues such as corneal edema, polypoid proliferation and hyalinization of the vessel wall, cystic formation of the lens, retinal nerve fiber layer degeneration, and corpora amylacea formation of the lacrimal gland. Conclusions: Prolonged usage of the nasal decongestant xylometazoline and its excipients may cause ophthalmic problems such as dry eyes, corneal edema, cataracts, retinal nerve fiber layer, and vascular damage in rats. Although these results were obtained from experimental animals, ophthalmologists should keep in mind the potential ophthalmic adverse effects of this medicine and/or its excipients and exercise caution with drugs containing xylometazoline, ethylene diamine tetra acetic acid, benzalkonium chloride and sorbitol for patients with underlying ocular problems.

RESUMO Objetivo: Investigar os possíveis efeitos da exposição crônica de descongestionante nasal e seus excipientes em tecidos oculares, utilizando um modelo experimental com ratos. Métodos: Sessenta ratos Wistar adultos machos foram divididos aleatoriamente em seis grupos. Os primeiros dois grupos foram controle (soro fisiológico) e Otrivina®. Os quatro grupos restantes receberam os excipientes de Otrivina, tais como Xilometazolina, Benzalcônio, Sorbitol e Ácido Etilenodiamino Tetracético (EDTA). Os medicamentos foram aplicados em ambas as narinas dos ratos, duas vezes ao dia, durante 8 semanas. Antes que os ratos fossem sacrificados, a coloração epitelial, o teste de Schirmer e a medida da pressão intraocular foram realizados sob anestesia com Ketamina/Xilasina (50 e 5 mg/kg, respectivamente). Resultados: Defeitos epiteliais e olho seco foram achados comuns nos grupos de estudo. A catarata desenvolveu-se clinicamente em dois casos. A avaliação histopatológica revelou a existência de alterações em todas as partes dos tecidos oculares, tais como edema de córnea, proliferação polipoide e hialinização da parede vascular, formação cística da lente, degeneração da camada de fibra nervosa da retina (RNFL) e formação de corpos amiláceos da glândula lacrimal. Conclusões: O uso prolongado do descongestionante nasal Xilometazolina e seus excipientes pode causar vários problemas oftalmológicos, como olho seco, edema de córnea, catarata, RNFL e dano vascular em ratos. Embora esses resultados tenham sido obtidos a partir de animais experimentais, os oftalmologistas devem ter em mente os potenciais efeitos oftalmológicos adversos desse medicamento e/ou de seus excipientes.

Drug exposure in early pregnancy might be related to the effects of increased maternal progesterone in implantation period.

AIM: This short communication aims to evaluate the relation in between drug exposure time and early pregnancy regarding gestational weeks. METHODS: The study covers the referrals made to the Department of Pharmacology for a teratogenic consultation in a 3-year period. From the recordings of pregnant women, the last menstrual period and the starting date of medication were used to determine the time of prescription with regard to gestational weeks. RESULTS: In all of the three years, potentially teratogenic medication was prescribed more frequently in the 3rd, 4th and 5th gestational weeks (in between 15-35 days of pregnancy). Approximately 75% of the pregnant women in the study were prescribed with drugs, most frequently with analgesics, antibiotics, gastrointestinal drugs and antidepressants, in these gestational weeks. CONCLUSIONS: The timing of prescriptions in early pregnancy frequently coincides with the increased levels of maternal progesterone in implantation period. Progesterone may lead to negative mood symptoms of an increased pain perception, anxiety, irritability and aggression in some of the pregnant women and therefore causes an increased stress condition which in turn may result in pain, infection and inflammation in the individual. Taking the frequently used medications into consideration, the reason for prescriptions in this period might be related to the symptoms originating from the effects of progesterone. Future studies are needed to better demonstrate this association of drug exposure and effects of maternal progesterone in early pregnancy.

Inhibitory Effect of Pycnogenol® on Airway Inflammation in Ovalbumin-Induced Allergic Rhinitis.

BACKGROUND: The supplement Pycnogenol® (PYC) has been used for the treatment of several chronic diseases including allergic rhinitis (AR). However, the in vivo effects on allergic inflammation have not been identified to date. AIMS: To investigate the treatment results of PYC on allergic inflammation in a rat model of allergic rhinitis. STUDY DESIGN: Animal experimentation. METHODS: Allergic rhinitis was stimulated in 42 rats by intraperitoneal sensitization and intranasal challenge with Ovalbumin. The animals were divided into six subgroups: healthy controls, AR group, AR group treated with corticosteroid (dexamethasone 1 mg/kg; CS+AR), healthy rats group that were given only PYC of 10 mg/kg (PYC10), AR group treated with PYC of 3mg/kg (PYC3+AR), and AR group treated with PYC of 10 mg/kg (PYC10+AR). Interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-10 (IL-10), and OVA-specific immunoglobulin E (Ig-E) levels of serum were measured. Histopathological changes in nasal mucosa and expression of tumor necrosis factor-α (TNF-α) and IL-1ß were evaluated. RESULTS: The levels of the IL-4 were significantly decreased in the PYC3+AR, PYC10+AR and CS+AR groups compared with the AR group (p=0.002, p<0.001, p=0.006). The production of the IFN-γ was significantly decreased in the PYC3+AR and PYC10+AR groups compared with the AR group (p=0.013, p=0.001). The administration of PYC to allergic rats suppressed the elevated IL-10 production, especially in the PYC3+AR group (p=0.006). Mucosal edema was significantly decreased respectively after treatment at dose 3 mg/kg and 10 mg/kg PYC (both, p<0.001). The mucosal expression of TNF-α has significantly decreased in the PYC3+AR and PYC10+AR groups (p=0.005, p<0.001), while the IL-1ß expression significantly decreased in the CS+AR, PYC3+AR, and PYC10+AR groups (p<0.001, p=0.003, p=0.001). CONCLUSION: PYC has multiple suppressive effects on allergic response. Thus, PYC may be used as a supplementary agent in allergic response.

Protective effect of Pycnogenol on cisplatin-induced ototoxicity in rats.

CONTEXT: Pycnogenol®, which is French maritime pine bark extract, is a potent antioxidant. It is used in medical conditions caused by oxidative stress. Cisplatin (cis-diamminedichloroplatinum II) is an antineoplastic agent. However, its serious side effects such as ototoxicity limit its usage. OBJECTIVE: Antioxidants can be used to prevent ototoxicity. We investigated the effect of Pycnogenol® on cisplatin-induced ototoxicity. MATERIALS AND METHODS: Rats were randomly assigned to four groups of five. Distortion product-evoked otoacoustic emissions (DPOAE) test was performed for each rat. The experimental groups were as follows: Control Group, Pycnogenol® Group: 10 mg/kg Pycnogenol® intraperitoneally for 7 days, Cisplatin Group: intraperitoneally 15 mg/kg single injection of cisplatin on the fifth day, Cisplatin + Pycnogenol® Group: intraperitoneally 10 mg/kg Pycnogenol® treatment for 7 days, additionally on the fifth day, 15 mg/kg single injection of cisplatin was given. On the eighth day, DPOAE was re-performed and rats were sacrificed. Apoptosis was evaluated histopathologically. RESULTS: Mean percentage of apoptotic cells was 1.5, 3, 30 and 11% in organ of Corti and 2, 2, 40, 15% in spiral ganglion neurons in Control Group, Pycnogenol® Group, Cisplatin Group and Cisplatin + Pycnogenol® Group, respectively. Cisplatin Group and Cisplatin + Pycnogenol® Group were significantly different when compared to Control Group histopathologically both in organ of Corti and spiral ganglion neuron (p <0.001, p = 0.019, p = 0.001, p = 0.015). DPOAE results showed that Cisplatin + Pycnogenol® Group was significantly different when compared to Cisplatin Group at 3, 6 and 8 kHz (p < 0.05). CONCLUSION: Pycnogenol protected against cisplatin ototoxicity. Also, pycnogenol is not ototoxic.

Biochemical and Histological Effects of Thiamine Pyrophosphate against Acetaminophen-Induced Hepatotoxicity.

The aim of this study was to investigate whether thiamine pyrophosphate (TPP) has biochemical and histological preventive effects on oxidative liver damage induced by paracetamol (APAP). Rats were divided into the following groups: healthy control (HG), APAP (AG, 1500 mg/kg, orally), thiamine pyrophosphate (TPPG, 100 mg/kg, intraperitoneally), APAP+NAC (ANAC, 100 mg/kg, intraperitoneally), APAP+TPP (ATPG) and APAP+NAC+TPP (ANTG). Oxidant, antioxidant parameters, liver function tests and histological assessment were performed between groups. Malondialdehyde levels in the AG, HG, TPPG, ANAC, ATPG and ANTG groups were 0.470 ± 0.210, 0.213 ± 0.004, 0.194 ± 0.001, 0.197 ± 0.06, 0.199 ± 0.008 and 0.173 ± 0.010 µmol/g protein, respectively. Total glutathione levels were 7.787 ± 0.395, 14.925 ± 0.932, 13.200 ± 0.984, 13.162 ± 0.486, 13.287 ± 0.787 and 13.500 ± 0.891 µm/g protein, respectively. In the AG group, marked liver damage occurred with the elevation of liver function tests and oxidative stress markers, such as malondialdehyde, myeloperoxidase and nitric oxide (p < 0.05). Biochemical results were congruent with the histological changes of oxidative damage. Compared to the AG group (p < 0.05), TPP significantly reduced oxidant parameter levels in the ATPG group and simultaneously increased the antioxidant parameter levels of catalase and glutathione. The histological changes were improved to almost normal hepatic structure. Moreover, TPP had nearly the same hepatoprotective effect as NAC, and there was statistically no additional benefit with NAC co-treatment. There was no statistically significant difference (p > 0.05) among the ANAC, ANTG and ATPG groups in terms of oxidant/antioxidant levels. TPP proved to be as efficacious as standard therapy and may be beneficial in APAP-induced hepatotoxicity.

Can tissue adhesives and platelet-rich plasma prevent pharyngocutaneous fistula formation?

OBJECTIVE: One of the frequently encountered disorders of wound healing following laryngectomy is pharyngocutaneous fistula. However, although studies have been performed with the aim of prevention of pharyngocutaneous fistulae, there are very few studies with tissue adhesives and platelet-rich plasma. In this study, our aim was to investigate the histopathologic changes in wound healing caused by various tissue adhesives and platelet-rich plasma, together with their effects on prevention of pharyngocutaneous fistula. METHODS: 40 male rats were randomly divided into five groups: control, platelet-rich plasma, fibrin tissue adhesive, protein-based albumin glutaraldehyde and synthetic tissue adhesive groups. The pharyngotomy procedure was performed and was sutured. Except the control group, tissue adhesives and platelet-rich plasma were applied. Then, the skin was sutured. On the seventh day, the rats were sacrificed. The skin was opened and pharyngotomy site was assessed in terms of fistulae. The pharyngeal suture line was evaluated histopathologically by using Ehrlich Hunt scale. RESULTS: Inflammatory infiltration was found to be higher in "platelet-rich plasma" group than "fibrin tissue adhesive" and "synthetic tissue adhesive" groups. The fibroblastic activity of "platelet-rich plasma", "fibrin tissue adhesive" and "protein-based albumin glutaraldehyde" groups was higher than the control group. The positive changes created by platelet-rich plasma and fibrin tissue adhesive at the histopathologic level were found together with no detected fistula. Among the study groups, there was no statistical difference for pharyngeal fistula development. This result may be obtained by the small number of animal experiments. CONCLUSION: These results shed light on the suggestion that platelet-rich plasma and fibrin tissue adhesive can be used in clinical studies to prevent pharyngocutaneous fistula.