Effects of weight intervention-induced changes in pathological fat mass of patients with extreme obesity and anorexia nervosa on adipokines and visceral adipocyte functions: a prospective, comparative, observational study.

OBJECTIVE: Adipose tissue is the largest endocrine organ in the human body, and as its mass changes, the serum levels of the molecules it secretes also change. Visceral adipose tissue index (VAI) is a simple surrogate marker of visceral adipose tissue dysfunction. This study evaluated the effects of changes in fat mass on adipocytokine behavior and VAI in patients with anorexia nervosa (AN) and extreme obesity (EO). PATIENTS AND METHODS: The study group consisted of three subgroups: Group 1, patients with EO who were candidates for obesity surgery with BMI≥50 kg/m2 (n=20). Group 2, newly diagnosed patients with AN (n=12). Group 3 controls with BMI 20-25 kg/m2 (n=20). The AN and EO groups were followed until at least a 10% weight change before and after the intervention. RESULTS: Prior to the intervention, EO patients exhibited the lowest levels of apelin, omentin, and adiponectin, while AN patients demonstrated the highest levels of these markers. Leptin and IL-6 were elevated in EO and reduced in AN patients. After treatment, all adipokines and VAI increased in AN patients, and omentin, adiponectin, and IL-6 increased in EO patients, while apelin, leptin, and VAI decreased. The change in each adipocytokine (∆) was positively correlated with the other adipocytokines (p<0.050) and negatively correlated with metabolic and VAI changes (p<0.050). The regression analysis determined that the following variables were associated with the change in adipose tissue mass: Δapelin (OR: 1.061; p=0.028) and Δadiponectin (OR: 1.057; p=0.036). CONCLUSIONS: In individuals with pathological adipocyte mass, the change in adipocytokine levels in response to weight change is not as expected. The fact that these changes are not seen in the early period of the weight intervention treatment indicates that these patients have compensatory physiological mechanisms to protect them. In addition, using VAI instead of BMI, whose reliability is increasingly questioned because it does not reflect body fat mass, can be considered an alternative. However, there may be modeling errors in the early stages of weight change and in AN and EO patients where metabolic parameters reach extreme values. Therefore, it should be tested in studies where larger patient groups are followed for a more extended period.

Validation of the Turkish version of Endometriosis Health Profile questionnaire (EHP-30) to evaluate the quality of life in women with endometriosis.

Background: The Endometriosis Health Profile-30 (EHP-30) is a commonly used tool for assessing the impact of endometriosis on a person's quality of life. The EHP-30 is a 30-item questionnaire that measures various aspects of endometriosis-related health, including physical symptoms, emotional well-being, and functional impairment. Objectives: EHP-30 has not yet been evaluated with Turkish patients. Therefore, we aim to develop and validate the Turkish version of EHP-30 in this study. Materials and Methods: This cross-sectional study was conducted with 281 randomly selected patients from Turkish Endometriosis Patient-Support Groups. The items of the EHP-30 distributed across 5 subscales of the core questionnaire are generally applicable to all women with endometriosis. There are 11 items on the pain scale, 6 on the control and powerlessness scale, 4 on the social support scale, 6 on the emotional well-being scale, and 3 on the self-image scale. The patients were asked to complete the form with brief demographic information and psychometric evaluation included factor analysis, convergent validity, internal consistency, test-retest reliability, data completeness and the determination of floor and ceiling effects. Main outcome measure: The main outcomes measures were the test-retest reliability, internal consistency, and the assessment of construct validity. Results: In this study, 281 completed questionnaires were included with a return rate of 91%. Data completeness was accepted as excellent on all subscales. Floor effects were found in medical profession (37%), children (32%) and work (31%) modules. No ceiling effects were found. Division of the core questionnaire into five subscales identical to the original EHP-30 was confirmed by factor analysis performed. The intraclass correlation coefficient for agreement varied from 0.822 to 0.914. There was agreement between the EHP-30 and EQ-5D-3L on both of the hypotheses that were tested. There was a statistically significant difference in scores between endometriosis patients and healthy women across in all subscales (p<.01). Conclusion: The results of this validation study for the EHP-30 indicated a high level of data completeness, with no significant floor or ceiling effects. The questionnaire demonstrated good internal consistency and excellent test-retest reliability. These findings confirm that the Turkish version of the EHP-30 is a valid and reliable toolfor measuring the health-related quality of life in individuals with endometriosis. What's new?: EHP-30 had not yet been evaluated with Turkish patients and the results of this study demonstrate the validity and reliability of the Turkish translation of the EHP-30 in assessing endometriosis patients' health-related quality of life.

The Relationship between the SUVmax Value Obtained in Ga-68 PSMA PET/CT and Lactate Dehydrogenase and Alkaline Phosphatase in Prostate Cancer

Objectives: ALP and LDH are serum markers of prognostic importance in prostate cancer patients. PET/CT imaging with Ga-68 PSMA has played an important role in prostate cancer imaging in recent years. Our aim in this study was to evaluate the relationship and prognostic significance between SUVmax values obtained with Ga-68 PSMA PET/CT and LDH and ALP levels in prostate cancer patients. Methods: We retrospectively evaluated 61 prostate cancer patients who had Ga-68 PSMA PET/CT imaging and who did not have a prostatectomy between 2019 and 2020. PSA, ALP and LDH levels were measured in all patients before or after imaging within a maximum of 28 days. Results: The median age of the patients included in this study was 73 (range: 57–89) and all 61 patients were prostatic adenocarcinoma. 50 (82%) of the patients had distant metastasis in Ga-68 PSMA PET/CT. There was a significant positive correlation between serum LDH and PSA levels. There was a positive correlation between serum ALP and PSA levels. A negative correlation was found between ALP levels and prostate SUVmax. Conclusions: While negative correlation was found between SUVmax and ALP levels, no correlation was found between LDH levels and SUVmax. High ALP levels were found to be related to metastasis rates and severity and high serum PSA levels (AU)

Objetivos: ALP y LDH son marcadores séricos deimportancia pronóstica en pacientes con cáncer de próstata.Las imágenes de PET/CT con Ga-68 PSMA han jugado unpapel importante en las imágenes de cáncer de próstata enlos últimos años. Nuestro objetivo en este estudio fue evaluar la relación y la importancia pronóstica entre los valores de SUVmax obtenidos con Ga-68 PSMA PET/CT ylos niveles de LDH y ALP en pacientes con cáncer de próstata.Métodos: Evaluamos retrospectivamente a 61 pacientes con cáncer de próstata que se sometieron a imágenes de PET/CT con Ga-68 PSMA y que no se sometierona prostatectomía entre 2019 y 2020. Los niveles de PSA,ALP y LDH se midieron en todos los pacientes antes o después de la obtención de imágenes en un plazo máximo de28 días.Resultados: La mediana de edad de los pacientes incluidos en este estudio fue de 73 (rango: 57–89) y los 61pacientes eran adenocarcinoma de próstata. 50 (82%) delos pacientes tenían metástasis a distancia en Ga-68 PSMAPET/CT. Hubo una correlación positiva significativa entrelos niveles séricos de LDH y PSA. Hubo una correlaciónpositiva entre los niveles séricos de ALP y PSA. Se encontró una correlación negativa entre los niveles de ALP y elSUVmáx prostático.Conclusiones: Si bien se encontró una correlaciónnegativa entre los niveles de SUVmáx y ALP, no se encontró correlación entre los niveles de LDH y el SUVmáx. Seencontró que los niveles altos de ALP estaban relacionadoscon las tasas de metástasis y la gravedad y los niveles altosde PSA en suero. (AU)

Relaciones entre el factor-1alfa inducido por hipoxia y los parámetros de la PET/TC con 18F-FDG en el cáncer colorrectal / Relationships between hypoxia induced factor-1alfa and 18F-FDG PET/CT parameters in colorectal cancer

OBJETIVO: El factor inducible para hipoxia (HIF-1) tiene un papel crítico en la homeostasis del oxígeno y es un activador transcripcional de angiogénesis, eritropoyesis, hierro y metabolismo de glucosa. La tasa de metabolismo de glucosa aumenta en algunos tumores a través de HIF-1alfa. Nuestro objetivo es evaluar la relación entre hipoxia en el cáncer colorrectal, los parámetros de PET, el tamaño del tejido necrótico y los factores pronósticos patológicos mediante el uso de HIF-1alfa. MATERIALES/MÉTODOS: 70 pacientes (28 mujeres/42 hombres; promedio de edad: 63 años) diagnosticados con cáncer colorrectal mediante biopsia, se estadificaron con PET/TC preoperatoria y se operaron posteriormente. La puntuación de evaluación inmunohistoquímica se realizó de acuerdo con la expresión de HIF-1alfa nuclear, la intensidad y la densidad de tinción. El volumen metabólico tumoral (MTV), la glucólisis de lesión total (TLG) y el volumen tumoral (TV) se calculó utilizando el volumen de una fórmula elipsoide mediante las imágenes de TC y el porcentaje de necrosis tumoral (%TmNcr) se calculó por diferencia entre TV y MTV. RESULTADOS: Hubo una correlación positiva moderadamente significativa entre el SUVmáx del tumor y TV y el %TmNcr (r=0,403, p = 0,001 y r=0,5, p = 0,0001, respectivamente). No hubo una relación estadísticamente significativa entre niveles de expresión de HIF-1alfa y SUVmáx tumoral, TLG, MTV, TV, %TmNcr, estadio tumoral, invasión linfovascular, invasión perineural y afectación ganglionar extracapsular/capsular. Por otro lado, se observó una fuerte tinción inmunohistoquímica nuclear en las células tumorales adyacentes al borde invasivo, las células inflamatorias. Aunque no fue estadísticamente significativa, se observó una tinción nuclear moderada o fuerte en el 64,9% de los pacientes metastásicos. CONCLUSIÓN: Aunque la presencia de una correlación positiva entre SUVmáx tumoral y el % de TmNcr muestra que hay células hipóxicas en tejido canceroso con una alta captación de FDG, no se demostró ninguna relación entre la presencia de HIF-1alfa y el incremento metabólico de glucosa y los factores patológicos del tumor. La fuerte tinción inmunohistoquímica nuclear en células tumorales adyacentes a las células inflamatorias y de borde invasivas nos hace pensar que HIF-1alfa desempeña un papel en el área de invasión del microambiente tumoral

AIM: The hypoxia-inducible factor 1 (HIF-1) has a critical role in oxygen homeostasis and it is a transcriptional activator of angiogenesis, erythropoiesis, iron and glucose metabolism. Glucose metabolism rate is increased in some tumours via HIF-1alfa. Our aim is to evaluate the relationship between hypoxia in colorectal cancer, PET parameters, necrotic tissue size and pathologic prognostic factors via using HIF-1alfa. MATERIALS/METHODS: 70 patients (28 female/42 male; median age: 63 years) who were diagnosed with colorectal cancer via biopsy were staged with preoperative PET/CT and operated subsequently. Immunohistochemical evaluation scoring was done according to nuclear HIF-1alfa expression, staining density and intensity. Metabolic tumour volume (MTV), total lesion glycolysis (TLG) and tumour volume (TV) were calculated by using volume of an ellipsoid formula via CT images, and percentage of tumour necrosis (%TmNcr) that was calculated by the difference between TV and recorded MTV. RESULTS: There was a moderately meaningful positive correlation between tumour SUVmax and TV and %TmNcr (r=0.403, p = 0.001 and r=0.500, p = 0.0001, respectively). There were no statistically significant relationships between HIF-1alfa expression levels and tumour SUVmax, TLG, MTV, TV, %TmNcr, tumour stage, lymphovascular invasion, perineural invasion and extracapsular/capsular lymph node involvement. On the other hand, strong nuclear immunohistochemical staining was seen in tumour cells adjacent to invasive border, inflammatory cells. Although not statistically significant, moderate or strong nuclear staining were seen in 64.9% of metastatic patients. CONCLUSION: Although the presence of a positive correlation between tumour SUVmax and %TmNcr shows that there are hypoxic cells in cancer tissue with high FDG uptake, the relationship between the presence of HIF-1alfa and enhanced glucose metabolism and pathological prognostic factors of tumour was not shown. Strong nuclear immunohistochemical staining in tumour cells adjacent to invasive border and inflammatory cells leads us to believe that HIF-1alfa plays a role in the invasion area of tumour microenvironment

Relationships between hypoxia induced factor-1α and 18F-FDG PET/CT parameters in colorectal cancer. / Relaciones entre el factor-1α inducido por hipoxia y los parámetros de la PET/TC con 18F-FDG en el cáncer colorrectal.

AIM: The hypoxia-inducible factor 1 (HIF-1) has a critical role in oxygen homeostasis and it is a transcriptional activator of angiogenesis, erythropoiesis, iron and glucose metabolism. Glucose metabolism rate is increased in some tumours via HIF-1α. Our aim is to evaluate the relationship between hypoxia in colorectal cancer, PET parameters, necrotic tissue size and pathologic prognostic factors via using HIF-1α. MATERIALS/METHODS: 70 patients (28 female/42 male; median age: 63 years) who were diagnosed with colorectal cancer via biopsy were staged with preoperative PET/CT and operated subsequently. Immunohistochemical evaluation scoring was done according to nuclear HIF-1α expression, staining density and intensity. Metabolic tumour volume (MTV), total lesion glycolysis (TLG) and tumour volume (TV) were calculated by using volume of an ellipsoid formula via CT images, and percentage of tumour necrosis (%TmNcr) that was calculated by the difference between TV and recorded MTV. RESULTS: There was a moderately meaningful positive correlation between tumour SUVmax and TV and %TmNcr (r=0.403, p=0.001 and r=0.500, p=0.0001, respectively). There were no statistically significant relationships between HIF-1α expression levels and tumour SUVmax, TLG, MTV, TV, %TmNcr, tumour stage, lymphovascular invasion, perineural invasion and extracapsular/capsular lymph node involvement. On the other hand, strong nuclear immunohistochemical staining was seen in tumour cells adjacent to invasive border, inflammatory cells. Although not statistically significant, moderate or strong nuclear staining were seen in 64.9% of metastatic patients. CONCLUSION: Although the presence of a positive correlation between tumour SUVmax and %TmNcr shows that there are hypoxic cells in cancer tissue with high FDG uptake, the relationship between the presence of HIF-1α and enhanced glucose metabolism and pathological prognostic factors of tumour was not shown. Strong nuclear immunohistochemical staining in tumour cells adjacent to invasive border and inflammatory cells leads us to believe that HIF-1α plays a role in the invasion area of tumour microenvironment.

The effects of N-acetylcysteine on cisplatin induced cardiotoxicity.

OBJECTIVES: Recent studies reported that oxidative stress is an important mechanism that contributes to cisplatin induced cardiotoxicity. In the present study, the effects of N-acetylcysteine (NAC), which is an antioxidant, on cisplatin induced cardiotoxicity were investigated in a rat model. METHODS: Thirty two rats were separated into 4 equal groups: Control, NAC-250, CP (cisplatin), CP+NAC. Rats in the experimental groups were treated with a single dose of cisplatin intraperitoneally (ip) (10 mg/kg) and NAC (ip, 250 mg/kg) for 3 consecutive days. At the end of the experiment, cardiotoxicity was determined from plasma CK-MB, LDH, cTnI and cardiac myosin light chain-1 (CMLC-1) levels. In the tissue samples, total oxidant capacity (TOC), total antioxidant capacity (TAC), lipid hydroperoxide (ROOH) and thiol levels were measured. The hearts were also analyzed histopathologically. RESULTS: It was determined that cisplatin increased the tissue TOC, ROOH levels and decreased TAC and thiol levels. NAC administration after cisplatin treatment was observed to have ameliorated histological and functional changes in heart. CONCLUSIONS: In conclusion, the results of this experimental study suggested that oxidative stress had a serious effect on cisplatin cardiotoxicity, and NAC could be used as a therapeutic agent in addition to standard cisplatin treatment protocols (Tab. 3, Fig. 1, Ref. 35).

A case of rudimentary horn pregnancy diagnosed after failed attempts at pregnancy termination.

We report a case of rudimentary horn pregnancy at 12 weeks gestation with fetal demise misdiagnosed ultrasonographically as an intrauterine pregnancy in a private clinic. The patient was referred to a tertiary care hospital after failed attempts at terminating her pregnancy. A definitive diagnosis was made with ultrasonography and magnetic resonance imaging (MRI) before uterine rupture ensued. Excision of the rudimentary horn and the ipsilateral fallopian tube was carried out by laparotomy. Failure to terminate pregnancy after several attempts should alert the physician about the possibility of a uterine anomaly and a pelvic MRI scan may help in the diagnosis of a suspected rudimentary horn pregnancy.

Effect of lidocaine spray in pain management during office-based endometrial sampling: A randomised placebo-controlled trial.

Office-based endometrial sampling is the most frequently performed gynaecological procedure. The procedure is usually associated with pain and discomfort. Several anaesthetic and analgesic techniques (e.g., non-steroidal anti-inflammatory drugs, paracervical block, misoprostol and topical anaesthetics) are used for pain management during endometrial sampling. There is no comprehensive study using lidocaine in spray form; we sought to investigate the analgesic efficacy of 10% lidocaine spray in patients undergoing office-based endometrial biopsy. We conducted a prospective, randomised (lidocaine spray (n = 60) and placebo (n = 60), respectively), double-blind study. The mean pain score during procedure was 3.51 ± 1.51 in the lidocaine spray group and 5.11 ± 1.66 in the placebo group. Lidocaine spray treatment significantly lowered the pain scores compared with placebo (p < 0.001). Lidocaine spray can be accepted as a non-invasive, easy to apply and more comfortable anaesthetic method for office-based endometrial sampling.

Effects of testicular histopathology on sperm retrieval rates and ICSI results in non-obstructive azoospermia.

Non-obstructive azoospermia (NOA) is characterised by absence of sperm in the ejaculate. Significant relationship between the pattern of the testis histopathology of NOA and successful sperm retrieval rate is well known. In this study, we assess efficacy of testicular histopathology on sperm retrieval rates and intracytoplasmic sperm injection results after microdissection testicular sperm extraction in cases of non-obstructive azoospermia. It is a retrospective analysis of 111 NOA patients who have histopathological confirmation. According to histopathological findings, the patients were divided into three groups: Sertoli-cell-only syndrome (SCOS), maturation arrest (MA) and hypospermatogenesis. Sperm retrieval rate was significantly higher in hypospermatogenesis group compared with that in SCOS and MA groups. In terms of fertilisation and clinical pregnancy rates, there was no significant difference between the groups. As a result, compared with MA and SCOS, hypospermatogenesis has higher sperm retrieval rates. Our study revealed that once successful sperm retrieval is achieved, fertilisation and clinical pregnancy rates are similar in NOA patients.

Apilarnil reduces fear and advances sexual development in male broilers but has no effect on growth.

1. An experiment was conducted to determine the possibility of stimulating sexual development at an early age in male and female broiler chickens by administration of apilarnil, a natural bee product, in the pre-pubertal period. 2. From 28 to 55 d of age, birds were given apilarnil orally. The effects of low (2.5 g/bird) and high (7.5 g/bird) doses of apilarnil on growth performance, testicular weight, secondary sexual characteristics, blood lipids, testosterone and fearful behaviour were evaluated. 3. Apilarnil administration did not cause a positive effect on growth performance of male and female broilers suggesting that apilarnil did not have an anabolic effect. 4. Apilarnil administration suppressed blood glucose and cholesterol. 5. Birds receiving apilarnil remained immobile for a shorter period in a tonic imobiliy test and showed less home-cage avoidance responses suggesting a lower level of fearfulness. 6. Increases in testicular weight, testosterone concentration and comb growth in males receiving apilarnil implied that it stimulates the sexual maturation at an early age. However, a similar stimulation of secondary sexual characteristics was not observed in females.

Car-borne survey of natural background gamma dose rate in Çanakkale region, Turkey.

Natural background gamma radiation was measured along roads in the environs of Çanakkale region by using a car-borne spectrometer system with a plastic gamma radiation detector. In addition, activity concentrations of ²³8U, ²²6Ra, ²³²Th and 4°K in soil samples from the Çanakkale region were determined by using a gamma spectrometer with an HPGe detector. A total of 92,856 data of the background gamma dose rate were collected for the Çanakkale region. The background gamma dose rate of the Çanakkale region was mapped using ArcGIS software, applying the geostatistical inverse distance-weighted method. The average and population-weighted average of the gamma dose are 55.4 and 40.6 nGy h⁻¹, respectively. The corresponding average annual effective dose to the public ranged from 26.6 to 96.8 µSv.

Socio-demographic and clinical characteristics of individuals with diagnoses of eating disorder in a university hospital in Istanbul.

OBJECTIVE: This paper reports the first-ever description of a clinical eating disorder population from Turkey. The aim of this study was to examine the socio-demographic and clinical characteristics of individuals with diagnosis of eating disorders (IDED) referred to a university psychiatry clinic in Istanbul between 2003 and 2009. METHOD: The diagnoses and subtype of 111 IDEDs, the referral type to the hospital, setting of treatment, and state of involuntary hospitalization were evaluated by interview and semi-structured questionnaire. RESULTS: The clinical sample included 64 individuals with anorexia nervosa (AN), 38 with bulimia nervosa (BN), and 9 with eating disorder not otherwise specified (EDNOS), including only one male. Younger individuals and those with a lower BMI were significantly more likely to be family referred and hospitalized involuntarily. DISCUSSION: The overall socio-demographic features of the sample are generally consistent with data collected in other communities. However, aspects of the clinical features, referral types of eating disorders and subtypes exhibit some characteristics peculiar to our sample.

The impact of rational pharmacotherapy training reinforced via prescription audit on the prescribing skills of fifth-year medical students.

OBJECTIVE: The aim of the study was to demonstrate the impact of a rational pharmacotherapy (RPT) clerkship reinforced via prescription audit (PA) on the prescribing skills of fifth-year medical students trained by both pharmacologists and clinicians at Gazi University Medical School. METHODS: The RPT training lasted for five days. A total of 101 medical students were included in the study. The students were asked to prescribe for standardized patients with uncomplicated essential hypertension. PA was performed on the prescriptions on the first (PA1) and last (PA2) days of the clerkship to determine the influence of the clerkship on the prescribing habits. The students were also asked to comment on PA with a short questionnaire at the end of the clerkship. The difference between PA scores was analyzed using the Mann-Whitney-Rank-Sum-test. RESULTS: Scores for PA1 and PA2 and the feedback of the medical students were compared. A significant improvement in PA scores was observed by the end of the clerkship. The commonest drugs in the prescriptions in both PA1 and PA2 were angiotensin-converting enzyme (ACE) inhibitors. The feedback from the medical students revealed that PA improved their prescription skills and that the trainers helped them to reach the targets, helped them to gain self-confidence and they agreed that PA should be applied in clinical pharmacology courses. CONCLUSIONS: RPT training reinforced via PA guided by clinicians and pharmacologists is helpful in improving the prescribing skills of medical students. ACE inhibitors were the commonest group of drugs chosen by the medical students both before and after the clerkship. Prescription audit together with the clerkship caused a significant improvement in all parts of the prescription determined by prescription audit. The cooperation of pharmacologists and clinicians helped the clerkship to reach the targets.

Effect of melatonin and time of administration on irradiation-induced damage to rat testes.

The effect of ionizing irradiation on testes and the protective effects of melatonin were investigated by immunohistochemical and electron microscopic methods. Eighty-two adult male Wistar rats were divided into 10 groups. The rats in the irradiated groups were exposed to a sublethal irradiation dose of 8 Gy, either to the total body or abdominopelvic region using a 60Co source at a focus of 80 cm away from the skin in the morning or evening together with vehicle (20% ethanol) or melatonin administered 24 h before (10 mg/kg), immediately before (20 mg/kg) and 24 h after irradiation (10 mg/kg), all ip. Caspace-3 immunoreactivity was increased in the irradiated group compared to control (P < 0.05). Melatonin-treated groups showed less apoptosis as indicated by a considerable decrease in caspace-3 immunoreactivity (P < 0.05). Electron microscopic examination showed that all spermatogenic cells, especially primary spermatocytes, displayed prominent degeneration in the groups submitted to total body and abdominopelvic irradiation. However, melatonin administration considerably inhibited these degenerative changes, especially in rats who received abdominopelvic irradiation. Total body and abdominopelvic irradiation induced identical apoptosis and testicular damage. Chronobiological assessment revealed that biologic rhythm does not alter the inductive effect of irradiation. These data indicate that melatonin protects against total body and abdominopelvic irradiation. Melatonin was more effective in the evening abdominopelvic irradiation and melatonin-treated group than in the total body irradiation and melatonin-treated group.

Effect of melatonin and time of administration on irradiation-induced damage to rat testes

The effect of ionizing irradiation on testes and the protective effects of melatonin were investigated by immunohistochemical and electron microscopic methods. Eighty-two adult male Wistar rats were divided into 10 groups. The rats in the irradiated groups were exposed to a sublethal irradiation dose of 8 Gy, either to the total body or abdominopelvic region using a 60Co source at a focus of 80 cm away from the skin in the morning or evening together with vehicle (20% ethanol) or melatonin administered 24 h before (10 mg/kg), immediately before (20 mg/kg) and 24 h after irradiation (10 mg/kg), all ip. Caspace-3 immunoreactivity was increased in the irradiated group compared to control (P < 0.05). Melatonin-treated groups showed less apoptosis as indicated by a considerable decrease in caspace-3 immunoreactivity (P < 0.05). Electron microscopic examination showed that all spermatogenic cells, especially primary spermatocytes, displayed prominent degeneration in the groups submitted to total body and abdominopelvic irradiation. However, melatonin administration considerably inhibited these degenerative changes, especially in rats who received abdominopelvic irradiation. Total body and abdominopelvic irradiation induced identical apoptosis and testicular damage. Chronobiological assessment revealed that biologic rhythm does not alter the inductive effect of irradiation. These data indicate that melatonin protects against total body and abdominopelvic irradiation. Melatonin was more effective in the evening abdominopelvic irradiation and melatonin-treated group than in the total body irradiation and melatonin-treated group.

Melatonin prevents inflammation and oxidative stress caused by abdominopelvic and total body irradiation of rat small intestine

We investigated the day-night differences in intestinal oxidative-injury and the inflammatory response following total body (TB) or abdominopelvic (AP) irradiation, and the influence of melatonin administration on tissue injury induced by radiation. Rats (male Wistar, weighing 220-280 g) in the irradiated groups were exposed to a dose of 8 Gy to the TB or AP region in the morning (resting period - 1 h after light onset) or evening (activity span - 13 h after light onset). Vehicle or melatonin was administered immediately before, immediately after and 24 h after irradiation (10, 2.0 and 10 mg/kg, ip, respectively) to the irradiated rats. AP (P < 0.05) and TB (P < 0.05) irradiation applied in the morning caused a significant increase in thiobarbituric acid reactive substance (TBARS) levels. Melatonin treatment in the morning (P < 0.05) or evening (P < 0.05) decreased TBARS levels after TB irradiation. After AP irradiation, melatonin treatment only in the morning caused a significant decrease in TBARS levels (P < 0.05). Although we have confirmed the development of inflammation after radiotherapy by histological findings, neither AP nor TB irradiation caused any marked changes in myeloperoxidase activity in the morning or evening. Our results indicate that oxidative damage is more prominent in rats receiving TB and AP irradiation in the morning and melatonin appears to have beneficial effects on oxidative damage irrespective of the time of administration. Increased neutrophil accumulation indicates that melatonin administration exerts a protective effect on AP irradiation-induced tissue oxidative injury, especially in the morning.

Melatonin prevents inflammation and oxidative stress caused by abdominopelvic and total body irradiation of rat small intestine.

We investigated the day-night differences in intestinal oxidative-injury and the inflammatory response following total body (TB) or abdominopelvic (AP) irradiation, and the influence of melatonin administration on tissue injury induced by radiation. Rats (male Wistar, weighing 220-280 g) in the irradiated groups were exposed to a dose of 8 Gy to the TB or AP region in the morning (resting period - 1 h after light onset) or evening (activity span - 13 h after light onset). Vehicle or melatonin was administered immediately before, immediately after and 24 h after irradiation (10, 2.0 and 10 mg/kg, ip, respectively) to the irradiated rats. AP (P < 0.05) and TB (P < 0.05) irradiation applied in the morning caused a significant increase in thiobarbituric acid reactive substance (TBARS) levels. Melatonin treatment in the morning (P < 0.05) or evening (P < 0.05) decreased TBARS levels after TB irradiation. After AP irradiation, melatonin treatment only in the morning caused a significant decrease in TBARS levels (P < 0.05). Although we have confirmed the development of inflammation after radiotherapy by histological findings, neither AP nor TB irradiation caused any marked changes in myeloperoxidase activity in the morning or evening. Our results indicate that oxidative damage is more prominent in rats receiving TB and AP irradiation in the morning and melatonin appears to have beneficial effects on oxidative damage irrespective of the time of administration. Increased neutrophil accumulation indicates that melatonin administration exerts a protective effect on AP irradiation-induced tissue oxidative injury, especially in the morning.

The effect of venlafaxine on ongoing and experimentally induced pain in neuropathic pain patients: a double blind, placebo controlled study.

BACKGROUND AND AIM: The aim of this randomized double blind placebo controlled study was to investigate the effectiveness and the safety of venlafaxine XR 75 and 150 mg on ongoing pain and on quantitative sensory tests in 60 patients with neuropathic pain for 8 weeks. METHODS: Evaluation parameters consisted of ongoing pain intensity (VAS), patient satisfaction, side effects, global efficacy and tolerance. Quantitative sensory measurements taken from the affected area before and after the drug treatment included pin-prick hyperalgesia, allodynia, detection and pain thresholds to electrical and heat stimuli, temporal summation of repetitive electrical and heat stimuli. RESULTS: A total of 55 patients completed the study. VAS scores decreased significantly compared to the baseline measurements in all groups. There was no significant difference between the groups regarding pain intensity and escape medication. The areas of allodynia and pin-prick hyperalgesia decreased significantly in venlafaxine groups compared to the placebo. There was no significant difference between the groups regarding the detection thresholds (electrical and heat). The pain threshold and the summation threshold to electrical stimuli and the summation threshold to heat stimuli increased significantly following treatment in both venlafaxine groups. In addition, the degree of the temporal summation to electrical and heat stimuli decreased significantly following treatment in both venlafaxine groups compared to the placebo. CONCLUSION: The study showed significant effect of venlafaxine in the manifestations of hyperalgesia and temporal summation, but not on the ongoing pain intensity. Furthermore, the quantitative sensory tests provided complementing information to the clinical measures.

A randomized trial of amifostine as radioprotector in the radiotherapy of head and neck cancer.

PURPOSE: Radiotherapy (RT) for head and neck cancer typically involves the major salivary glands bilaterally and can cause acute and chronic xerostomia and mucositis. The degree of xerostomia has been reported to depend on the radiation dose and the salivary gland volume irradiated. In this study, we evaluated the efficacy of the radioprotector amifostine to improve xerostomia and mucositis in head and neck cancer patients who received RT. PATIENTS AND METHODS: A total of 53 patients with head and neck cancer entered this prospective randomized study. Patients were randomly assigned to undergo RT or RT plus short intravenous (i.v.) infusion of amifostine 210 mg/m(2) before each RT fraction. RESULTS: No statistically significant difference was seen between the 2 arms in terms of mucositis. Acute xerostomia occurred in 31 (93.9%) patients in the amifostine arm and all of the patients in the RT-alone arm (p <0.05). Grade 3 acute xerostomia occurred in 13 (39.3%) patients in the amifostine arm, and in 9 (45%) patients in the RT-alone arm (p=0.04). Late xerostomia occurred in 19 (57.5%) patients in the amifostine arm, and in 14 (70%) patients in RT-alone arm (p=0.03). CONCLUSION: The administration of amifostine in head and neck cancer patients receiving RT improved significantly acute and late xerostomia, while did not offer protection in the prevention of mucositis. Further prospective studies are needed in order to better define the role of this agent.