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Raynaud-Claes syndrome is rare condition characterized with intellectual disability and is caused by X-linked pathogenic variants in CLCN4 gene. Hemizygous missense variant NM_001830.4: c.1597G>A (p.V533M) was detected in a 6-year-old male followed up with intellectual disability, dysmorphism, and epileptic encephalopathy. The mother and one sister of the patient were also carrying the same variant. The clinical picture of the patient was significantly more severe, and the patient exhibited nonconvulsive status. Tonic status was observed with benzodiazepine treatment and the patient was successfully treated with a ketogenic diet. Many types of seizures can be seen in Raynaud-Claes syndrome, some of which can be life-threatening. CLCN4 variants can be investigated in patients who exhibit an increase in tonic seizures with benzodiazepine treatment. However, ketogenic dietary therapy as first-line treatment can be lifesaving in resistant epilepsy cases caused by the CLCN4 gene.

Kültepe-Kanesh, located 20 km northeast of Kayseri province, rises on the fertile plain that stretches to the north of Erciyes Mountain and is irrigated by Sarımsaklı Stream. The settlement area, which consists of two parts, the Kanesh mound and the lower city, is 2,5 km in diameter. With these dimensions, Kültepe is one of the largest Bronze Age cities not only in Anatolia but also in the whole ancient Near East. This article presents the initial findings related to the construction levels of Kültepe-Kanesh, one of the key settlements for ancient Near Eastern archeology, dated to the end of the third millennium BC-the beginning of the second millennium BC. Monumental buildings from the Early Bronze Age III, located in the southwest of the Kültepe mound, were replaced by modest dwellings and workshops with overlapping building levels. This trend appears to have continued for approximately one and a half to two centuries, as no traces of public, administrative or religious structures have been found in recent excavations. In contrast to the architectural field, pottery traditions and styles, such as the Alişar III ware and monochrome pottery, show continuity in the Middle Bronze Age. The new excavations indicate that the settlement continued uninterrupted during that period and it offers important opportunities to analyze the traces of socio-economic change that took place in and around Central Anatolia at the end of the third millennium BC, with architectural remains.

Objective: Prader-Willi Syndrome (PWS) is the most common genetic cause of obesity. Prevention and management of obesity, which represents the main cause of morbidity and mortality in these patients, is essential. Ketogenic diet (KD) is used in the treatment of various disorders, however knowledge of its effect in PWS is lacking. The present study assesses the characteristics of patients with PWS who were on KD., Design and Patients: This is a retrospective, cross-sectional descriptive study investigating the subjects with PWS, who had received KD for at least 6 months., Results: Ten patients with PWS [median age 52.5 (47-77) months] complied with KD. The median treatment period was 16.5 [11-52] months. Of the daily calorie, 75%-85% were from fat, and 15%-25% from protein + carbohydrate. The baseline body weight standard deviation (SD) score before diet therapy was 2.10 [-1.11-4.11], whereas it was 0.05 [-0.92-1.2] at final evaluation (p = .007). The baseline median BMI SD score before diet therapy was 3.05 [-0.21-3.72], whereas it was 0.41 [-0.87-1.57] at final evaluation (p = .002). The height SD score remained unchanged. Mild hypercholesterolaemia was the most common biochemical abnormality during treatment with KD., Conclusion: Our results indicate that KD might have a favourable effect on weight management in PWS., (© 2022 John Wiley & Sons Ltd.)

The study aimed to investigate the best-performing of three risk calculators (RCs) for the Turkish population in predicting cancer-free status and high-risk prostate cancer (PCa) in patients undergoing transrectal ultrasound-guided prostate biopsy. The electronic medical records of 527 patients who underwent prostate biopsy for the first time due to PSA of 0.3-50 ng/dl and/or cancer suspicion at digital rectal examination (DRE) between January 2017 and December 2020 were retrieved retrospectively. The predictive power of the RCs in the biopsy and the surgical cohort was calculated by two urologists using European Randomised Study of Screening for Prostate Cancer (ERSPC) RC, the North American Prostate Cancer Prevention Trial-RC (PCPT-RC), and the Prostate Biopsy Collaborative Group (PBCG)-RC. All three RCs were successful in predicting PCa and high-risk disease at ROC analysis (p < 0.0001). Of these three nomograms, PBCG-RC outperformed PCPT-RC 2.0 and ERSPC-RH in predicting benign pathology outcomes at biopsy. A better performance of PBCG-RC was also observed in terms of prediction of high-risk disease at biopsy. Using any of the available RCs prior to biopsy is of greater assistance to prostate-specific antigen and DRE than examination alone. The study results show that PBCG-RC performed before biopsy has a higher predictive power than the other two RCs., (© 2021 Wiley-VCH GmbH.)

Aims: To investigate the effect of ketogenic diet on motor function and daily living activities in children with epilepsy., Methods: A total of 62 children (median age 5.0 years) were enrolled. Motor function was assessed using the Gross Motor Function Measure (GMFM), and daily living activities and cognitive functions were assessed using the Functional Independence Measure (WeeFIM) before treatment and 3, 6, and 12 months after ketogenic diet treatment., Results: Significant improvement in total GMFM and WeeFIM scores ( P < .001) were found during the 12 months of ketogenic diet treatment. There was a positive correlation between total GMFM scores and WeeFIM scores at baseline (r= 0.792, P = .0001), and at 3 (r= 0.780, P = .0001), 6 (r= 0.744, P = .0001), and 12 months (r= 0.692, P = .0001) of treatment. Both the responder (50 patients, 80.7%) and nonresponder (12 patients, 19.3%) patient groups showed significantly higher GMFM and WeeFIM scores at 12 months of treatment compared to baseline values. A ≥50% reduction in seizure frequency was observed in 77.4%, 72.6%, and 80.7% of the patients after 3, 6, and 12 months of treatment, respectively., Conclusion: Ketogenic diet treatment improves motor functions and daily living activities in children with epilepsy during the 12 months of treatment.

Background/aim: Diabetes mellitus (DM) is one of the most common metabolic diseases seen in the world today. Diabetic neuropathy (DN) is a chronic complication of the disease that is rarely reported in children, since it has a relatively longer latency period. Our main objective in this study is to determine the incidence rate of DN in pediatric DM patients and assess the risk factors associated with DN., Materials and Methods: Data from 111 patients from January 2011 to May 2014 were reviewed in a retrospective manner. Nerve conduction studies were performed as the gold standard in diagnosis., Results: The incidence rate of symptomatic DN was 13.5% according to our study results. The EMG-diagnosed DN incidence rate was calculated as 22.5%. Following linear regression analysis, positive correlation was found between diabetes duration, diabetic ketoacidosis, and DN presence., Conclusion: Our study results demonstrate the fact that poor metabolic control, especially during early stages of the disease, is a major risk factor for neuropathy development. Planning prospective studies with long-term evaluations on nerve conduction in children with DM will be beneficial for this subject.

Because of the lack of studies comparing the efficacy and safety of levetiracetam and valproate before the induction of general anesthesia in the treatment of convulsive refractory status epilepticus in children, we aimed to compare the effectiveness of these antiepileptic drugs in patients with convulsive status epilepticus admitted to the Pediatric Intensive Care Unit between 2011 and 2014. Forty-six (59%) of the 78 patients received levetiracetam, and 32 (41%) received valproate for the treatment of refractory status epilepticus. The response rate was not significantly different between the 2 groups. Although no adverse event was noted in patients who received levetiracetam, 4 (12.5%) patients in the valproate group experienced liver dysfunction (P = .025). According to our results, levetiracetam and valproate may be used in the treatment of refractory status epilepticus before the induction of general anesthesia. Levetiracetam appears as effective as valproate, and also safer., (© The Author(s) 2016.)

Background The association between ketogenic diet (KD) and prolonged QT interval, life-threatening ventricular arrhythmias, and sudden death is controversial. Aim We aimed to prospectively evaluate the effect of KD on electrocardiography (ECG) measures in children with refractory epilepsy. Method A total of 70 children with drug-resistant epilepsy who received a KD for at least 12 months were included in the study. The standard 12-lead electrocardiography was performed in all patients before the beginning and in the 12th month of KD. Heart rate, P-wave duration and dispersion, corrected QT interval and QT dispersion, and Tp-e interval were measured. Results All ECG-derived parameters, but P-wave dispersion increased after 12 months of KD compared with the baseline values. However, these changes were not statistically significant. Conclusion A 12-month long 3:1 KD treatment exerts no deleterious effect on cardiac repolarization measures., (Georg Thieme Verlag KG Stuttgart · New York.)

Ketogenic diet (KD) is one of the most effective therapies for intractable epilepsy. Olive oil is rich in monounsaturated fatty acids and antioxidant molecules and has some beneficial effects on lipid profile, inflammation and oxidant status. The aim of this study was to evaluate the serum lipid levels of children who were receiving olive oil-based KD for intractable seizures at least 1 year. 121 patients (mean age 7.45 ± 4.21 years, 57 girls) were enrolled. At baseline and post-treatment 1, 3, 6, and 12 months body mass index-SDS, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride levels were measured. Repeated measure ANOVA with post hoc Bonferroni correction was used for data analysis. The mean duration of KD was 15.4 ± 4.1 months. Mean total cholesterol, LDL-cholesterol and triglyceride levels were significantly higher at 1st, 3rd, 6th and 12th months of the KD treatment, compared to pre-treatment levels (p = 0.001), but showed no difference among during-treatment measurements. Mean body mass index-SDS and HDL-cholesterol levels were not different among the baseline and follow-up time points (p = 0.113 and p = 0.067, respectively). No child in this study discontinued the KD because of dyslipidemia. Even if rich in olive oil, high-fat KD causes significant increase in LDL-cholesterol and triglyceride levels. More studies are needed to determine the effect of KD on serum lipids in children using different fat sources in the diet.

Objective: We aimed to determine the midterm effect of a ketogenic diet on serum lipid levels, carotid intima-media thickness, and the elastic properties of the carotid artery and the aorta in patients with intractable epilepsy., Methods: A total of 52 children aged between 12 months and 18 years with intractable epilepsy who started the ketogenic diet from September 2014 to September 2015 were included into this prospective study. Carotid intima-media thickness and the elastic properties of the carotid artery and the aorta were assessed by echocardiography in all cases before beginning of the ketogenic diet and after at least 12 months on the ketogenic diet., Results: Twenty-one patients at the third month and 25 patients at the first year of the ketogenic diet were seizure free. A reduction of greater than 90% in the seizure frequency was achieved in three patients at the sixth month and in five patients at the first year of the treatment. The serum levels of total cholesterol, low-density lipoprotein, and triglyceride were increased significantly at a median of 12.6 months (range: 12 to 13.5 months) of the ketogenic diet treatment, whereas serum levels of high-density lipoprotein did not change. Carotid intima-media thickness, aortic and carotid strain, the stiffness index, distensibility, and elastic modulus did not change after 12 months of the ketogenic diet therapy., Conclusion: Olive oil-based ketogenic diet appears to have no disturbing effect on the carotid intima-media thickness and the elastic properties of the aorta and the carotid artery in epileptic children, although it may be associated with increased concentrations of serum lipids., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The aim of this prospective study is to investigate the effect of a 6-month-long ketogenic diet on carotid intima-media thickness, carotid artery, and aortic vascular functions. Thirty-eight drug-resistant epileptic patients who were being treated with ketogenic diet were enrolled. Fasting total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, total cholesterol, and glucose concentrations were measured and echocardiography was performed in all patients before the beginning of ketogenic diet and at the sixth month of treatment. The body weight, height, body mass index, serum levels of triglyceride, total cholesterol, and low-density lipoprotein increased significantly at month 6 when compared to baseline values (P < .05). Carotid intima-media thickness, elastic properties of the aorta, and carotid artery did not change at the sixth month of therapy compared to baseline values. A 6-month-long ketogenic diet has no effect on carotid intima-media thickness and elastic properties of the carotid artery and the aorta., (© The Author(s) 2015.)

Objective: Our primary aim was to determine the short-term effects of a ketogenic diet on cardiac ventricular function in patients with refractory epilepsy., Methods: Thirty-eight drug-resistant epileptic patients who were treated with a ketogenic diet were enrolled in this prospective study. Echocardiography was performed on all patients before beginning the ketogenic diet and after the sixth month of therapy. Two-dimensional, M-mode, color flow, spectral Doppler, and pulsed-wave tissue Doppler imaging measurements were performed on all patients., Results: The median age of the 32 patients was 45.5 months, and 22 (57.8%) of them were male. Body weight, height, and body mass index increased significantly at the sixth month of therapy when compared with baseline values (P < 0.05). Baseline variables assessed by conventional M-mode echocardiography showed no significant difference at month 6 (P > 0.05). Doppler flow indices of mitral annulus and tricuspid annulus velocity of patients at baseline and month 6 showed no significant differences (P > 0.05). Tricuspid annular E/A ratio was lower at month 6 (P < 0.05). Although mitral annulus tissue Doppler imaging studies showed no significant difference (P > 0.05), there was a decrease in Ea velocity and Ea/Aa ratio gathered from tricuspid annulus at month 6 compared with baseline (P < 0.05)., Conclusion: A 6-month duration ketogenic diet does not impair left ventricular functions in children with refractory epilepsy; however, it may be associated with a right ventricular diastolic dysfunction., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The aim of this study is to evaluate the types and clinical characteristics of peripheral facial palsy in children. The hospital charts of children diagnosed with peripheral facial palsy were reviewed retrospectively. A total of 81 children (42 female and 39 male) with a mean age of 9.2 ± 4.3 years were included in the study. Causes of facial palsy were 65 (80.2%) idiopathic (Bell palsy) facial palsy, 9 (11.1%) otitis media/mastoiditis, and tumor, trauma, congenital facial palsy, chickenpox, Melkersson-Rosenthal syndrome, enlarged lymph nodes, and familial Mediterranean fever (each 1; 1.2%). Five (6.1%) patients had recurrent attacks. In patients with Bell palsy, female/male and right/left ratios were 36/29 and 35/30, respectively. Of them, 31 (47.7%) had a history of preceding infection. The overall rate of complete recovery was 98.4%. A wide variety of disorders can present with peripheral facial palsy in children. Therefore, careful investigation and differential diagnosis is essential., (© The Author(s) 2013.)

Background: Levetiracetam has been proven to be effective in both partial and generalized seizures in children. However, few studies have reported its efficacy in the treatment of acute repetitive seizures. We aimed to investigate the efficacy and safety of levetiracetam in children with acute repetitive seizures., Methods: The medical records of children from the age of 1 month-18 years who received levetiracetam because of acute repetitive seizures in the pediatric intensive care unit between 2010 and 2013 were reviewed retrospectively., Results: Of the 133 patients, levetiracetam terminated seizures in 104 (78.2%). Side effects such as agitation and aggression were observed in three patients (2.2%). The likelihood of treatment failure was increased by four times by younger age at seizure onset; by six times in the individuals with neurological abnormalities; and by 22 times in the patients with West syndrome. The patients who used levetiracetam as the first treatment option for acute repetitive seizures had a longer duration of epilepsy, a higher rate of neurological abnormality, and a higher proportion of medically resistant epilepsy compared with the individuals who used levetiracetam as an add-on treatment to the other intravenous antiepileptic drugs. However, no differences were detected between these two groups in terms of treatment response., Conclusions: Intravenous levetiracetam appears to be effective and safe in the treatment of acute repetitive seizures. Randomized clinical trials are needed to determine whether intravenous levetiracetam may replace other antiepileptic drugs as the first-line therapy in the management of acute repetitive seizures., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: Quadruple test is used for Down's syndrome screening in the second trimester of pregnancy. The aim of this study was to investigate differences in quadruple test parameters between pregnancies achieved by assisted reproductive treatments (ART) and spontaneous conception., Materials and Methods: We retrospectively compared levels of alfa-fetoprotein (AFP), unconjugated Estriol (uE3), inhibin-A and hCG and also screen positive test results., Results: Levels of all quadruple test parameters were statistically significantly increased in ART pregnancies when compared to spontaneous pregnancies, AFP was 1.4±0.74 and 1.16±0.53, (p=0.001), uE3 was 1.10±0.37 and 1.00±0.28, (p=0.004), hCG was 1.56±1.04 and 1.26±0.76, (p=0.001), inhibin A was 1.38±0.76 and 1.08±0.57, (p=0.001), screen positive tests were nearly doubled (4.8% and 8.4%)., Conclusions: Increased screen positive test results and quadruple test parameters in ART pregnancies may lead to unnecessary amniocentesis.

Background: Limited data are available on the effects of a ketogenic diet on dispersion duration of P-wave and QT-interval measures in children. We searched for the changes in these measures with serial electrocardiograms in patients treated with a ketogenic diet., Methods: Twenty-five drug-resistant patients with epilepsy treated with a ketogenic diet were enrolled in this study. Electrocardiography was performed in all patients before the beginning and at the sixth month after implementation of the ketogenic diet. Heart rate, maximum and minimum P-wave duration, P-wave dispersion, and maximum and minimum corrected QT interval and QT dispersion were manually measured from the 12-lead surface electrocardiogram., Results: Minimum and maximum corrected QT and QT dispersion measurements showed nonsignificant increase at month 6 compared with baseline values. Other previously mentioned electrocardiogram parameters also showed no significant changes., Conclusions: A ketogenic diet of 6 months' duration has no significant effect on electrocardiogram parameters in children. Further studies with larger samples and longer duration of follow-up are needed to clarify the effects of ketogenic diet on P-wave dispersion and corrected QT and QT dispersion., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Limited data are available for the effectiveness of the antiepileptic drugs in children in daily clinical practice. The aim of this study was to investigate the efficacy and tolerability of the first prescribed old and new antiepileptic drugs in children with newly diagnosed idiopathic epilepsy during a 12-month period., Method: A total of 289 children (141 females and 148 males) who received phenobarbital (n=33), valproate (n=142), carbamazepine (n=42), oxcarbazepine (n=38), or levetiracetam (n=34) as the first-line treatment, were enrolled in the study. Seizure control and the occurrence of adverse events were assessed during a treatment period of 12 months., Results: Overall, 245 (84.8%) patients remained seizure-free during the study period. The rate of seizure control did not differ significantly between the drug groups (p=0.099). Forty-four (15.2%) patients including 1 (3.0%) treated with phenobarbital, 22 (15.5%) with valproate, 7 (16.7%) with carbamazepine, 10 (26.3%) with oxcarbazepine, and 4 (11.8%) with levetiracetam had treatment failure. There was no significant difference between seizure-free and failure groups in terms of age, gender, seizure type, and drugs used. Overall, 80 (27.7%) patients had adverse events, of those the most common ones were behavioral problems, nausea and/or vomiting, weight gain, and learning difficulties. The reasons for treatment failures were lack of seizure control in 29 (10.0%) patients and intolerable adverse events in 15 (5.2%) patients., Conclusion: It appears that old (phenobarbital, valproate and carbamazepine) and new antiepileptic drugs (oxcarbazepine and levetiracetam) have similar efficacy and tolerability profiles. Institutional ethic number is 28.3.2013/14., (Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: In this study, it was aimed to describe the clinical, histopathological and genetic features of 20 patients with gamma sarcoglycanopathy confirmed by muscle biopsies and genetic analysis., Material and Method: We retrospectively reviewed 20 patients from whom muscle biopsy specimens were obtained between 2007 and 2012. All patients were clinically diagnosed as muscular dystrophy and biopsy materials were collected from five different centers of neurological disorders. All DNAs were extracted from muscle tissues or blood samples of patients and genetic tests (mutation analyses for gamma sarcoglycan gene and deletion-duplication analyses for all 4 sarcoglycan genes) were performed., Results: The mean age of the patients was 7.6 years (2 -21 years). Only one case (5%) was older than 14 years. The mean CPK level was 10311 U/L (1311 - 35000 U∕L). There were 4 siblings in these series. Expression defects of gamma sarcoglycan staining were determined in (15 males, and 5 females) all patients with muscle biopsy specimens. But only in 9 of them, disease-causing defects could be determined with genetic analyses., Conclusion: The present study has demonstrated that both examination of muscle biopsy specimens and DNA analysis remain important methods in the differential diagnosis of muscular dystrophies. Because dystrophinopathies and sarcoglycanopathies have similar clinical manifestation.

Background: Recurrent peripheral facial palsy is uncommon in children. It mostly occurs as an idiopathic disorder and to a lesser extent in the setting of some infectious, genetic, or systemic disorders. However, its association with familial Mediterranean fever has not been reported before., Patient: We present a 14-year-old girl who experienced three episodes of right-sided peripheral facial palsy during a 9-month interval. She had a diagnosis of familial Mediterranean fever (homozygous with M694V mutation) and she had been receiving colchicine for 8 years. Recurrent peripheral facial palsy could be a neurological manifestation of vasculitis in familial Mediterranean fever., Conclusion: Recurrent peripheral facial palsy may be a manifestation of familial Mediterranean fever in children., (Copyright © 2013 Elsevier Inc. All rights reserved.)

A series of 2-(hydrazinocarbonyl)-3-substituted-phenyl-1H-indole-5-sulfonamides and 1-({[5-(aminosulfonyl)-3-phenyl-1H-indol-2-yl]carbonyl}amino)-2,4,6 trimethylpyridinium perchlorates possessing various 2-, 3- or 4-substituted phenyl groups with methyl-, halogeno- and methoxy-functionalities, as well as the perfluorophenyl moiety, have been evaluated as inhibitors of the beta-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic fungi Cryptococcus neoformans (Can2) and Candida albicans (CaNce103). Both enzymes were potently inhibited by these sulfonamides, K(I)s in the range of 4.4-118 nM against Can2, and of 5.1-128 against CaNce103, respectively. Minor structural changes in the 3-substituted phenyl moiety contribute significantly to the inhibitory activity. Some of the investigated sulfonamides showed promising selectivity ratios for inhibiting Can2 over the host, human enzymes CA I and II., (Copyright 2010 Elsevier Ltd. All rights reserved.)

3H-Spiro[1,3-benzothiazole-2,3'-indol]-2'(1'H)-ones 3a-c and 4a-e were synthesized from treating the 5-substituted 1H-indole-2,3-diones with 2-aminothiophenol in ethanol. The structures were confirmed by elemental analyses, spectrometry (IR, (1)H NMR, (13)C NMR, HSQC-2D and LCMS-APCI) and single crystal X-ray analysis. The new compounds were screened for their antioxidant activities such as the Fe(3+)/ascorbate system induced inhibition of lipid peroxidation (LP) in liposomes, trolox equivalent antioxidant capacity (TEAC), scavenging effect on diphenylpicryl hydrazine (DPPH*), and reducing power. These compounds showed potent scavenging activities against DPPH* and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS*(+)) radicals, reducing powers, and strong inhibitory capacity on lipid peroxidation. Compound 4a incorporating methyl both at R(1) and R(2) was found to be the most potent antioxidant described in this study. Compounds 3b and 4b were selected as representative compounds by the National Cancer Institute for screening against anticancer activity and these compounds were found to be cytotoxic against CNS cancer cell line SNB-75 in the primary screen., (Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.)

A series of 2-(hydrazinocarbonyl)-3-substituted-phenyl-1H-indole-5-sulfonamides possessing various 2-, 3- or 4- substituted phenyl groups with methyl-, halogeno- and methoxy- functionalities, as well as the perfluorophenyl moiety have been synthesized and evaluated as inhibitors of both α- and β-class carbonic anhydrases (CAs, EC 4.2.1.1). All human isoforms with medicinal chemistry applications were included in such studies, among which CA I, II, VA, VB, VII, IX and XII. Several low nanomolar, sometimes isoform-selective compounds were thus detected. Two β-CAs from the pathogenic bacterium Mycobacterium tuberculosis encoded by the genes Rv1284 Rv3588c were also highly inhibited (sometimes in the sub-nanomolar range) by some pyridinium derivatives incoprorating this scaffold, obtained from the corresponding 2-(hydrazinocarbonyl)-3-substituted-phenyl-1H-indole-5-sulfonamides by reaction with pyrylium salts. The fungal β-CAs from Candida albicans (Nce103) and Cryptococcus neoformans (Can2) were also investigated for their inhibition with this family of sulfonamides and some highly effective inhibitors detected. As the X-ray crystal structure of one such sulfonamide with the human isoform CA II is also know, the 3-substituted-phenyl-1H-indole-5-sulfonamides represent a totally new class of inhibitors obtained by structure-based drug design, which show efficiency in inhibiting both α- and β-CAs from several species.

A series of new 2-aryl-4-thiazolidinones (3 and 4) was synthesized from 2-hydroxy-2,2-diphenyl-N'-[(substituted phenyl)methylene]acetohydrazides (2) and mercaptoacetic acid or 2-mercaptopropionic acid. The antimycobacterial activity of these compounds was determined and several leads with 95-99% inhibition at 6.25 microg/mL test concentration were identified. In addition, antitumor activities were measured against several tumor cell lines, and significant growth inhibition was observed for compound 4p. Taken together, 2-aryl-4-thiazolidinones were shown to be promising scaffolds for both antimycobacterial and tumor-targeting compounds.

Objectives: We evaluated the inflammatory reactions induced by three commonly used nonabsorbable suture materials in a rabbit model., Methods: Three suture materials were tested: braided polyester suture (Ethibond), braided blend of polyester and polyethylene suture (FiberWire), and monofilament polypropylene suture (Polypropylene). Thirty-six rabbits were randomly allocated to three suture groups, equal in number. Each suture type was placed bilaterally in the quadriceps muscle, patellar tendon, knee joint capsule, and Achilles tendon. Six animals in each group were sacrificed in the third and sixth weeks. The inflammation induced by each suture was assessed using light microscopy and the width of the inflammation zone (WIZ) was measured., Results: Ethibond was found to cause the most severe reaction in the muscle and tendon in the third week; in the sixth week, however, it showed the lowest inflammatory reaction in all tissue types. Reaction to Propylene was moderate in the third week, whereas it caused the largest WIZ in all tissue types in the sixth week, such that the eventual size of the WIZ induced by Propylene (6.6 + or - 2.1 mm) was significantly greater than that of Ethibond (1.6 + or - 0.9 mm) in muscle specimens (p<0.05). Except for the largest WIZ seen in joint capsule specimens in the third week, inflammatory reactions associated with FiberWire were low or moderate in all tissue specimens throughout the study. FiberWire was associated with some necrotic areas in two muscle and one tendon specimens., Conclusion: The extent of inflammatory reaction to nonabsorbable suture materials depends on the type of suture material, tissue type, and the duration of postoperative time.

A series of aromatic/heterocyclic sulfonamides incorporating phenyl(alkyl), halogenosubstituted-phenyl- or 1,3,4-thiadiazole-sulfonamide moieties and thienylacetamido; phenacetamido and pyridinylacetamido tails were prepared and assayed as inhibitors of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic human (h) hCA I and hCA II, and the mitochondrial hCA VA and hCA VB. The new compounds showed moderate inhibition of the two cytosolic isoforms (K(I)s of 50-390nM) and excellent inhibitory activity against the two mitochondrial enzymes, with many low nanomolar inhibitors detected (K(I)s in the range of 5.9-10.2nM). All substitution patterns explored here lead to effective hCA VA/VB inhibitors. Some hCA VA/VB selective inhibitors were also detected, with selectivity ratios for inhibiting the mitochondrial over the cytosolic isozymes of around 55.5-56.9. As hCA VA/VB are involved in several biosynthetic processes catalyzed by pyruvate carboxylase, acetyl CoA carboxylase, and carbamoyl phosphate synthetases I and II, providing the bicarbonate substrate to these carboxylating enzymes involved in fatty acid biosynthesis, their selective inhibition may lead to the development of antiobesity agents possessing a new mechanism of action.

A series of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides has been derivatized by reaction with 2,4,6-trimethylpyrylium perchlorate, leading to pyridinium derivatives. The new sulfonamides were evaluated as inhibitors of two beta-carbonic anhydrases (CAs, EC 4.2.1.1) from Mycobacterium tuberculosis, Rv1284 and Rv3273. The whole series showed excellent nanomolar inhibitory activity, with several subnanomolar inhibitors being detected. Rv1284 and Rv3273 have potential for developing antimycobacterial agents with an alternate mechanism of action.

A series of aromatic/heterocyclic sulfonamides incorporating phenyl(alkyl), halogenosubstituted-phenyl- or 1,3,4-thiadiazole-sulfonamide moieties and thienylacetamido; phenacetamido- and pyridinylacetamido tails were prepared and assayed as inhibitors of cytosolic human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I, II and VII. The new compounds showed moderate inhibition of the two ubiquitous isoforms I and II (K(I)s of 50-390 nM) and excellent inhibitory activity against the brain associated hCA VII (K(I)s in the range of 4.7-8.5 nM). Isoform VII highly selective inhibitors are being detected for the first time, with selectivity ratios for inhibiting CA VII over CA II of 11-75, and for inhibiting CA VII over CA I of 10-49, which may be useful for understanding the role of CA VII in epileptogenesis and other physiologic processes.

A series of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides possessing various 2-, 3- or 4- substituted phenyl groups with methyl-, halogeno- and methoxy-functionalities, or a perfluorophenyl moiety, has been derivatized by reaction with 2,4,6-trimethylpyrylium perchlorate. The new sulfonamides were evaluated as inhibitors of four mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, that is, CA I, II (cytosolic), CA IX and XII (transmembrane, tumor-associated forms). Excellent inhibitory activity was observed against hCA IX with most of these sulfonamides, and against hCA XII with some of the new compounds. These compounds were generally less effective inhibitors of hCA II. Being membrane impermeant, these positively-charged sulfonamides are interesting candidates for targeting the tumor-associated CA IX and XII, as possible diagnostic tools or therapeutic agents.

A series of 2-(hydrazinocarbonyl)-3-substituted-phenyl-1H-indole-5-sulfonamides possessing various 2-, 3- or 4-substituted phenyl groups with methyl-, halogeno- and methoxy-functionalities, as well as the perfluorophenyl moiety, have been evaluated as inhibitors of an alpha-carbonic anhydrase (CA, EC 4.2.1.1) of the nematode model organism Caenorhabditis elegans (CAH-4b, or ceCA). The substitution pattern at the 3-phenyl ring highly influenced the ceCA inhibitory activity of these heterocyclic sulfonamides, with best inhibitors (K(I)s in the range of 6.0-13.4 nM) incorporating 3-methyl-, 4-methyl-, 2-/3-/4-fluoro-, 4-chloro- and 3-/4-bromo-phenyl such moieties. Some of these sulfonamides also showed a good selectivity profile for the inhibition of the nematode over the human isozymes CA I and II (selectivity ratios in the range of 1.78-4.95 for the inhibition of ceCA over hCA II). These data can be used for the design of possibly new antihelmintic drugs, since the genome of many parasitic nematodes encode for a multitude of orthologue CA isozymes to ceCA investigated here.

A series of 2-(hydrazinocarbonyl)-3-substitutedphenyl-1H-indole-5-sulfonamides possessing various 2-, 3- or 4- substituted phenyl groups with methyl-, halogeno- and methoxy- functionalities, as well as the perfluorophenyl moiety have been synthesized and evaluated as inhibitors of 13 catalytically active, mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, that is, CA I-CA XV (of human (h) or murine (m) origin). The new compounds were ineffective inhibitors of isozymes hCA III, hCA IV, hCA VA, hCA VB, hCA VI and mCA XIII, moderate inhibitors of hCA I, hCA VII, hCA IX and mCA XV, and excellent, low-nanomolar inhibitors of hCA II and hCA XIV. The substitution pattern of the aromatic group in the 3-position of the indole ring influenced biological activity and isozyme inhibition profiles in this series of sulfonamides. Some of the best and most selective hCA XIV and mCA XV inhibitors ever reported have been identified in this study.

New series of 5-methyl/trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazones 3a-t, 1-methyl-5-methyl/trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazones 4a-y and 5-trifluoromethoxy-1-morpholinomethyl-1H-indole-2,3-dione 3-thiosemicarbazones 5a-m were synthesized. The structures of the synthesized compounds were confirmed by spectral data and elemental analysis. The new 5-methyl/trifluoromethoxy-1H-indole-2,3-dione derivatives, along with previously synthesized 5-methyl-1H-indole-2,3-dione 3-thiosemicarbazones 6a-l, were evaluated for in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv. 5-Methyl-1H-indole-2,3-dione 3-thiosemicarbazones (3b, 3d, 3f, 6c, 6d, and 6f), 5-trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazones (3q-s) and 5-trifluoromethoxy-1-morpholinomethyl-1H-indole-2,3-dione 3-thiosemicarbazones (5e and 5j-l) were found to be the most potent inhibitors of M. tuberculosis growth described in this study.

In the title compound, C(24)H(28)N(2)O(3)S, the pendant methyl C atom bonded to the cyclo-hexane ring is disordered over two sites in a 0.580 (11):0.420 (11) ratio. The cyclo-hexane ring adopts a distorted chair conformation while the thia-zolidine ring has an envelope conformation. The two phenyl rings make a dihedral angle of 71.8 (2)° with each other. The conformation is stabilized by an intra-molecular N-H⋯O hydrogen bond. In the crystal structure, an inter-molecular hydrogen bond O-H⋯O occurs.

Increasing use of more aggressive treatment approaches in patients with hematologic malignancies leads to an increased frequency of invasive fungal infections, which is a major cause of transplant-related mortality in hematopoietic stem cell recipients. In this respect, the presence of an active fungal infection prior to transplantation may hinder subsequent hematopoietic stem cell transplantation (HSCT); which sometimes is the only curative treatment. We report here the results of 13 consecutive patients transplanted with active fungal infection. Thirteen patients (7 males and 6 females) with a median age of 34 years (range, 16-53 years) underwent 15 HSCT between September 2003 and April 2007. In this group of 15 patients, consisting of hematologic malignancies with high risk of relapse or severe aplastic anemia, 11 (73%) transplants performed in subjects with active invasive fungal infection (IFI) patients survived 30 days after transplantation. Three patients (1 patient with primary disease relapse, 1 patient with graft versus host disease [GVHD] complicated with fungal pneumonia, and 1 patient with severe sinusoidal obstruction syndrome and GVHD complicated with aspiration pneumonia) died on days +66, +74, and +62 posttransplantation, respectively, within the first 100 days of HSCT. After a median follow-up time of 306 days (range, 145-680 days), four of 13 (31%) patients with active IFI were alive and disease free. Among a population of HSCT recipients with a dismal prognosis without transplantation, performing the procedure despite active IFI saved a considerable proportion of the patients. The presence of active IFI did not seem to be an absolute contraindication for HSCT, particularly among high-risk patients in whom a treatment delay could be fatal.

2-(Hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide was tested for its interaction with 12 carbonic anhydrase (CA, EC 4.2.1.1) isoforms in the search of compounds with good inhibitory activity against isozymes with medicinal chemistry applications, such as CA I, II, VA, VB, VII, IX, and XII among others. This sulfonamide is a potent inhibitor of CA I and II (K(I)s of 7.2-7.5 nM), a medium potency inhibitor of CA VII, IX, XII, and XIV, and a weak inhibitor against the other ubiquitous isoforms, making it thus a very interesting clinical candidate for situations in which a strong inhibition of CA I and II is needed. The crystal structure of the hCA II adduct of this sulfonamide revealed many favorable interactions between the inhibitor and the enzyme which explain its strong low nanomolar affinity for this isoform but may also be exploited for the design of effective inhibitors incorporating bicyclic moieties.