Assessing the binding interaction of polystyrene sulfonate with amitriptyline in healthy volunteers: a cross-over design - The BIND study.

PURPOSE: Polystyrene sulfonate is used for binding potassium in patients with chronic kidney disease (CKD). Because of its binding properties, it can potentially bind other medications and thereby decrease their bioavailability and effectiveness. Amitriptyline, often used by CKD patients for neuropathic pain, shows significant binding to polystyrene sulfonate in vitro. The purpose of this study was to determine the effect of polystyrene sulfonate on the exposure of amitriptyline in vivo when taken concomitantly in healthy volunteers. METHODS: We performed a prospective cross-over study in nine healthy volunteers. Participants were 18 years of age or older, did not use any medication, and had no known allergy to amitriptyline or polystyrene sulfonate. Participants visited Deventer Teaching Hospital twice. Once they received a single dose of amitriptyline 50 mg and once they received a single dose of both polystyrene sulfonate 15 g and amitriptyline 50 mg taken concomitantly, with a wash out period of at least 1 week. After intake of the medication, six blood samples were collected, at 2, 3, 4, 5, 6, and 8 h. Blood samples were analysed to determine maximum concentration (Cmax) and area under the curve 0-8 h after intake (AUC0-8 h). Difference in Cmax and AUC0-8 h was analysed with a paired T-test or Wilcoxon signed rank test, depending on normality of the data. A p-value < 0.05 was considered statistically significant. RESULTS: Of the nine participants included, eight participants completed both visits to the hospital. Mean maximum concentration (Cmax) of amitriptyline was 35.61 µg l-1 (95% CI 27.90-43.33 µg l-1) when taken alone, compared to 9.25 µg l-1 (95% CI 6.59-11.92 µg l-1) when taken with polystyrene sulfonate (p < 0.001). Mean AUC0-8 h of amitriptyline was 168.20 µg × h l-1 (95% CI 139.95-196.45 µg × h l-1) when taken alone and 45.78 µg × h l-1 (95% CI 30.20-61.36 µg × h l-1) when taken with polystyrene sulfonate (p < 0.0001). CONCLUSION: These results show a significant decrease in exposure of amitriptyline of approximately 75% when taken concomitantly with polystyrene sulfonate, thereby probably compromising therapy efficacy. Patients using both amitriptyline and polystyrene sulfonate should be informed to separate intake of these medications. TRIAL REGISTRATION: NL8539 (17 April 2020).

Correction of Areolar Protuberance During Augmentation Mammoplasty in Transfemale Patients.

Augmentation mammoplasty refers to "top surgery" for transfemale patients. Before this surgery, due to the hormonal treatment being taken, it may be encountered that there would be a glandular tissue of breast that seems to be similar to the simple tuberous breast disease, which is one of the diseases in female breast development. The presence of areolar protuberance in transfemale would of course undermine the cosmetic gain after augmentation mammoplasty operation. This situation, which can be difficult to diagnose before surgery especially in transfemale patients, will manifest itself clearly after the end of augmentation mammoplasty. As a precaution, resection of a part of glandular tissue equal to the protruding height of the areola from the posterior wall of the gland is an effective method both in terms of its simple applicability and not to use of an extra skin incision while performing augmentation mammoplasty.

Exploring co-dispensed drug use in patients on sevelamer or polystyrene sulfonate to identify potential novel binding interactions: a cross sectional in silico study : Potential novel binding interactions with resins.

Background Sevelamer and polystyrene sulfonate are used for treating hyperphosphatemia and hyperkalaemia in chronic kidney disease patients. Because of their binding properties, these resins potentially bind other drugs in the gastrointestinal tract, thereby decreasing their bioavailability and clinical effectiveness. Aim The aim of this study was to explore co-dispensed drug use in patients on sevelamer or polystyrene sulfonate to identify potential novel binding interactions. Method In this in silico study, the 100 drugs most frequently co-dispensed with sevelamer/polystyrene sulfonate in the period 2000-2018 were extracted from the University Groningen IADB.nl database. Drugs dispensed to < 5% of patients, drugs not orally administered, drugs administered once daily before bedtime and drugs for which information on binding interactions with sevelamer or polystyrene was already available were excluded. The likelihood of an interaction (yes or no) of the included drugs was assessed based on pKa- and Log P values. For sevelamer, drugs with a pKa (acid) between 1.5 and 7.4 and or a Log P value > 2.0 were identified as potential interacting drug. For polystyrene sulfonate, drugs with a pKa (base) > 1.5 were identified as potential interacting drug. Results Of the top 100 drugs most frequently co-dispensed with sevelamer/polystyrene sulfonate, 22 and 27 potentially clinically relevant new interacting drugs were identified for sevelamer and polystyrene sulfonate respectively. Conclusion Several potentially relevant novel binding interactions for sevelamer and polystyrene sulfonate were identified based on dispensing data and assessment of chemical properties for which further interaction research is warranted.

Outcome of Very Low and Low Birth Weight Infants with Esophageal Atresia: Results of the Turkish Esophageal Atresia Registry.

INTRODUCTION: The data of the Turkish Esophageal Atresia Registry (TEAR) was evaluated to define the outcome of very low birth weight (VLBW) and low BW (LWB) infants with esophageal atresia (EA). MATERIALS AND METHODS: The data registered by 24 centers between 2014 and 2018 were evaluated for demographic features, prenatal findings, associated anomalies, surgical treatment, and outcome. Patients were enrolled in three groups according to their BWs (VLBW <1,500 g), LWB = 1,500-2,500 g), and normal BW (NBW; >2,500 g). RESULTS: Among the 389 cases, there were 37 patients (9.5%) in the VLBW group, 165 patients (42.4%) in the LBW group, and 187 patients (48.1%) in the NBW group. Prenatal diagnosis rates were similar among the three groups (29.7, 34.5, and 24.6%, respectively). The standard primary anastomosis was achieved at a significantly higher rate in NWB cases than in the other groups (p < 0.05). In patients with tracheoesophageal fistula (TEF), patients of the NBW group had significantly higher rates of full oral feedings, when compared with VLBW and LBW cases (p < 0.05). At the end of the first year, when we evaluate all patients, the number of cases with fistula recanalization and esophageal anastomotic strictures (AS) requiring esophageal dilatation was similar among the groups. The weight and height measurements at 6 months and 1 year of age of the survivors were similar in all the groups. The overall mortality rate was significantly higher in the VLBW and LBW groups, when compared with the NBW patients, even in patients with tension-free anastomosis (p < 0.05). The incidence of the associated anomalies was 90.6% in cases with mortality, which was significantly higher than in survivors (59.6%; p < 0.05). According to Spitz's classification, the survival rate was 87.1% in class I, 55.3% in class II, and 16.7% in class III. The most common causes of mortality were associated with cardiovascular diseases, pneumonia, and sepsis. CONCLUSION: The national data of TEAR demonstrates that the developmental and feeding parameters are better in NBW patients. Although VLBW patients have higher risk of developing fistula canalization than the LBW and NBW groups, long-term complications, such as anastomotic strictures, weight, and height values, after 1 year are similar in both groups. According to our results, associated anomalies and LBWs are still significant risk factors for mortality in cases with EA.

A serious complication of liver hydatid cysts in children: cystobiliary fistulas.

AIM: We aimed to determine predictive factors for predicting cystobiliary fistulas (CBF) in children after treatment of liver hydatid cyst (LHD). METHODS: The records of patients who were treated for LHD between 01.06.2009 and 1.06.2019 were retrospectively reviewed. Age, sex, laboratory test results, size and number of cysts, method of first intervention (percutaneous or surgery), whether or not CBF developed and how it was treated were investigated. Among findings, those could be predictive were investigated. Data were evaluated with SPSS 21.0 program, p < 0.05 was considered significant. RESULTS: Of the 97 patients, 48 (49.5%) were male, 49 (50.5%) female, the mean age was 11.2 years, Eighty patients had right (82.5%), 13 had left, and 4 had bilobar involvement. As first intervention, surgery was performed in 39 (40.2%); percutaneous treatment was performed in 58 (59.8%) patients. In 8 patients (20.5%) in surgery group and in 6 patients (10.3%) in percutaneous group, totally in 14 patients (14.4%), CBF developed. The mean cyst diameter of CBF-developed group was 114.36 mm, and of CBF-undeveloped group was 74.30 mm. There was no statistically significant differences between groups in terms of age, sex, involved lobe, other organ involvement, and preoperative results (p > 0.5). There was a significant relationship between the cyst diameter and the rate of CBF development in both surgical and percutaneous groups (p < 0.05). ROC analysis was performed, and the cut-off value for the development of CBF detected as 69 mm for children. Since obstructive jaundice seen in adults is not common in children, an increase in liver function tests and bilirubin levels were not seen in our patients. CONCLUSION: A significant correlation was found only between the size of the cyst and developing CBF. Cysts greater than 69 mm have a higher risk of developing CBF after both percutaneous and surgical treatment and should be closely monitored.

COMPARISON OF CARDIAC ARRHYTHMIA TYPES BETWEEN HYPERTHYROID PATIENTS WITH GRAVES' DISEASE AND TOXIC NODULAR GOITER.

PURPOSE: Previous studies have demonstrated the relationship between hyperthyroidism and increased risk of cardiac arrhythmias. The most common causes of hyperthyroidism are Graves' disease (GD) and toxic nodular goiter (TNG). The aim of our study was to demonstrate if the underlying mechanism of hyperthyroidism, in other words autoimmunity, has an impact on the type of cardiac arrhythmias accompanying hyperthyroidism. METHOD: Twenty patients with TNG and 16 patients with GD who had overt hyperthyroidism were included in the study. Age, sex, thyroid hormone levels, thyroid autoantibody positivity, thyroid ultrasonography and scintigraphy results were recorded. 24-hour Holter ECG monitoring was performed in all patients. RESULTS: Mean age was significantly higher in the TNG group compared to the GD group (62.9±11.5 vs. 48.9±8.6 years, p=0.001). Free T3 was significantly higher (7.87±3.90 vs. 5.21±1.53 pg/mL, p=0.033) in the GD group while free T4 and TSH levels were similar between the two groups. In 24-hour Holter ECG recordings nonsustained ventricular tachycardia (VT) rates were significantly higher in the GD group than in TNG group [18.75% (n=3/16) vs. 0% (n=0/20), respectively, (p=0.043)]. Paroxysmal atrial fibrillation (AF) rates were significantly higher in the TNG group compared to GD group [(30% (n=6/20) vs. 0% (n=0/16), respectively, (p=0.016)]. CONCLUSION: Although free T3 levels were lower, paroxysmal AF rates were found significantly higher in the TNG group which may be associated with significantly higher age of this group. On the other hand, higher rate of nonsustained VT in the GD group may be related to either significantly higher free T3 levels or autoimmunity.

3,3 diindolylmethane leads to apoptosis, decreases sperm quality, affects blood estradiol 17 ß and testosterone, oestrogen (α and ß) and androgen receptor levels in the reproductive system in male rats.

3,3 Diindolylmethane (DIM) is a major digestive product of indole-3 carbinol, obtained from Brassica family vegetables such as broccoli, cabbage and Brussels sprouts. This study aimed to investigate the effects of DIM on sperm parameters, histological structures of testicular tissues, blood testosterone (T) and estradiol 17-ß (E2) in male rats. Thirty-eight male Sprague Dawley rats were used. Rats were divided into four groups: Group I: referred as Control group, received corn oil only; Group II: as DIM-10, rats received 10 mg kg-1 DIM; Group III: as DIM-50, rats received 50 mg kg-1 DIM; Group IV: as DIM-100, received 100 mg kg-1 DIM during 53 days. Spermatological parameters, malondialdehyde (MDA) levels of testes and serum T and E2 levels were assayed. Histopathological examinations of tests were done. DIM caused an increase in MDA levels. It decreased motility and live sperm rates and increased degeneration of testicular tissues. While DIM-10 did not affect abnormal sperm rate, higher concentrations increased the abnormalities. Sperm density was higher in DIM-10 groups when compared to both other groups. Only DIM-50 had an anti-androgenic effect among all groups. Only, DIM-10 showed anti-estrogenic activity as compared to higher DIM groups. In conclusion, DIM (i) had side effect on some sperm characteristics, (ii) increased the MDA levels and (iii) led to histological degeneration of testicular tissues and apoptosis in a dose-dependent manner.

A Deletion Mutation of the Connexin 26 (Gjb2) Gene in a Turkish Patient with Vohwinkel Syndrome .

Vohwinkel syndrome (VS), also known as keratoderma hereditaria mutilans, is a rare keratinization genetic disorder characterized by palmoplantar keratoderma, skeletal dysmorphisms and varying degrees of sensorineural deafness. Its mode of inheritance is autosomal-dominant, with mutations in loricrin and connexin 26 (GJB2) genes that manifest during infancy and boceme more evident during adulthood. We herein report a case of VS in a 23-year-old female exhibiting sensorineural hearing loss, palmar keratoderma and homozygous deletion mutation delE120 (c.358-360delGAG) in the GJB2 gene. VS, is a rare genetic disorder, should be considered in patients with palmoplantar keratoderma and hearing loss and should be investigated connexin 26 (GJB2) gene mutation.

The protective effect of the proteasome inhibitor bortezomib on the uterus of ovariectomized rats.

Bortezomib (BORT) is an anti-tumour agent that inhibits proteasome, which is responsible for the degradation of many intracellular proteins. Although some side-effects and chemotherapeutic effects of BORT are known, there has not been enough research regarding its effects on different tissues of proteasome inhibition in the senile period (post-menopausal). The aim of this study was to investigate the safety of using BORT during the post-menopausal period. The post-menopausal effects of BORT were investigated on ovariectomized (OVX) Spraque-Dawley rats. The female rats were separated into three groups: control, ovariectomized (OVX), and OVX + BORT. OVX and OVX + BORT groups consisted of six rats in each. BORT was administered intraperitoneally in a dosage of 0.2 mg/kg two days a week for four weeks after OVX. The uteri of the rats were investigated using morphometrical, histopathological, and immunohistopathological methods. A striking atrophy in the endometrium and myometrium was observed due to an estrogen deficiency in the OVX group. The partial protective effect of BORT administration was observed morphometrically and histopathologically. In immunohistochemical research, cytoplasmic NF-KB activity was observed in the presence of proteasome inhibition in the endometrium. In light of these findings, the limited protective effects of post-menopausal BORT administration are worth mentioning.

Nigella sativa as a potential therapy for the treatment of lung injury caused by cecal ligation and puncture-induced sepsis model in rats.

We investigated the potential protective effects of Nigella sativa (NS) on mortality, serum levels of proinflammatory cytokines, oxidative stress and histopathological changes in lung tissues, in cecal ligation and puncture (CLP)-induced sepsis model in rats. Sepsis induction by CLP, determination of serum cytokine levels by ELISA, spectrophotometric determination of oxidative stress parameters, and histological examination of lung tissues. The rat groups were: 1) CLP group, 2) sham group, 3) NS500-sham group, 4) NS125, 5) NS250, 6) NS500 groups. NS treatment significantly decreased proinflammatory cytokine levels in serum; LPO level, MPO activity, and pathological changes in lung tissues, in CLP-induced sepsis, while significantly increasing GSH levels and SOD activity in the lung tissue. NS treatment after CLP potentially reduced mortality and may exert effects through the reduction in tissue oxidative stress and serum cytokines. The histopathological changes were minimized in lung tissue by NS, under sepsis conditions. We can suggest that NS reverses the systemic inflammatory reaction to polymicrobial sepsis and thereby reduces multiple organ failure. It may be suggested that role of the NS ethanolic extract in preventing formation of CLP induced sepsis, is due to the anti-inflammatory and antioxidant effects of the different compounds of the black seeds.