MURCS association and rectovestibular fistula: case report of a patient treated with one-stage posterior sagittal anorectoplasty and sigmoid loop vaginoplasty

MURCS association is rare, first described by Duncan in 1979, including nonrandom association of Mullerian duct aplasia or hypoplasia (MU), renal agenesis or ectopy (R), and cervicothoracic somite dysplasia. A 5-year-old girl was admitted to the clinic with a complaint of anteriorly located anus. Physical and radiologic examination of the patient found MURCS association with anorectal malformation (ARM) of rectovestibular-type fistula. She had multiple vertebral anomalies, left renal agenesis, vaginal and uterine agenesia, with a normal female 46,XX karyotype. Posterior sagittal anorectoplasty (PSARP) and sigmoid loop vaginal reconstruction was performed as a one-stage operation for the treatment of vaginal agenesis and ARM. There were no complications in the postoperative period. This combined one-stage operation can be used easily in the treatment of some components of the MURCS association such as vaginal agenesis and ARM as an associated anomaly. J Pediatr Surg 38:262-264.     

Tc-99m MIBI uptake and its relation to the proliferative potential of brain tumors

PURPOSE: Many studies have shown that the S-phase fraction is a reflection of the proliferation potential of tumors, and DNA aneuploidy is more common in malignant tumors. In this preliminary study, the authors assessed the Tc-99m MIBI uptake of brain tumors and its relation to tumor grade and DNA content of the tumor cells. METHODS: Ten patients (eight male, two female; mean age, 53.2 +/- 6.11 years) with untreated brain tumors were included in the study. SPECT imaging was performed 20 minutes after injection of 740 MBq (20 mCi) Tc-99m MIBI. A single detector camera with a low-energy high-resolution collimator was used for image acquisition. A region of interest was drawn in the tumor area under magnetic resonance guidance. A Tc-99m MIBI uptake index was computed as the mean tumor-to-background ratio. Flow cytometric analysis of fresh tumor tissue specimens was performed immediately. The percentages of cells in the G0/G1, S, and G2/M phases were determined for each patient. RESULTS: DNA aneuploidy was found in 4 (49%) patients, whereas diploidy was found in 6 (60%) patients. There was a significant positive correlation between the Tc-99m MIBI uptake and the percentage of the S-phase fraction of the cell cycle ( = 0.000, r = 0.95). The Tc-99m MIBI index was significantly greater in aneuploid tumors than in diploid tumors ( < 0.01). CONCLUSIONS: High-grade brain tumors have increased Tc-99m MIBI uptake compared with that of low-grade tumors. Tc-99m MIBI uptake is correlated with the percentage of the S-phase fraction of the cell and the aneuploidy level of the brain tumor. This preliminary report suggests that Tc-99m MIBI imaging may be useful in the evaluation of the biologic characteristics of brain tumors.     

Protective effect of IGF-1 on experimental liver cirrhosis-induced common bile duct ligation

BACKGROUND/AIMS: The causes of malnutrition in liver cirrhosis are multifactorial. Levels of IGF-1 (insulin like growth factor-1) that is a crucial regulator of intermediary metabolism decreases. The aim of this study was to analyze the effect of IGF-1 supplementation during liver cirrhosis induced by common bile duct ligation. METHODOLOGY: Rats were divided into five different groups: One sham and four experimental groups. Rats in three of four groups were treated with 2 micrograms/day IGF-1 with a different time of experiment in each group. Blood biochemical parameters, tissue malondialdehyde, glutathione levels and the activity of tissue antioxidant enzymes and conventional and immunohistochemical analysis of liver samples were studied for each group. RESULTS: Serum albumin, total protein, fibrinogen levels decreased and prothrombin time was prolonged in the bile duct ligated and transected experimental group but not in the IGF-I treated rats compared with the rats in sham group. Liver malondialdehyde levels significantly increased in control group but not in IGF-1 treated groups. The activities of antioxidant enzymes were decreased compared with the other groups. Histopathology findings of liver biopsy demonstrated intense degree fibrosis and overexpression of fibroblast growth factor and desmin in the control group but a lesser degree of those in the IGF-1 treated groups. CONCLUSIONS: IGF-1 treatment improves liver function and decreases oxidative liver damage and histopathological findings. Further studies are required to delineate the mechanisms of protective effects of IGF-1.     

Sporadic hereditary pancreatic desmoid tumor: a new entity?

Deeply seated aggressive fibromatosis also termed as desmoid tumors are rare tumors that invade surrounding structures. Although they never metastasize mortality rate may be as high as 10% due to their aggressive local behavior. Intraabdominal desmoid tumors are usually associated with familial poliposis coli and have a high recurrence rate regardless of the therapy instituted. Sporadic cases are very rare and generous surgical excision may be of benefit. We hereby report 2 siblings with sporadic pancreatic desmoid tumors who also harbor additional fibrotic masses in the pelvis. Although in previously reported cases there is usually a triggering event such as trauma, in the present cases there was no inciting event. Furthermore, the cases are without an associated FAP history, which provides the first clinical clue of a possible genetic determinant in this rare disorder.     

Ochratoxin A reduces NMDA receptor subunits 2A and 2B concentrations in rat hippocampus: partial protective effect of melatonin

Ochratoxin A (OTA) is a mycotoxin produced by several fungi. Many foods can be contaminated by OTA, which is consequently found in the blood of humans and animals. It is known that OTA accumulates in the brain. The aim of this study was to investigate the effects of OTA on the brain. For this purpose, the effect of OTA on N-methyl-D-aspartate (NMDA) receptor subunits 2A (NR2A) and 2B (NR2B) in the hippocampus and the protective effect of melatonin were investigated. Three groups of eight rats were used: controls, OTA-treated rats (OTA dose 289 microg/kg per day) and OTA+melatonin-treated rats (melatonin dose 10 mg/kg per day). After four weeks of treatment, electrophoretic examinations were performed using SDS-polyacrylamide gel electrophoresis and Western blotting of hippocampal homogenates of the different groups. The concentrations of NR2A and NR2B in the OTA group were significantly lower than in the control group. The concentration of NR2B was significantly increased when melatonin was co-administered with OTA compared with OTA only. There was also a significant increase in NR2A levels when melatonin was co-administered with OTA. As a result, subchronic administration of OTA reduced hippocampal NMDA receptor subunits 2A and 2B concentrations in rats. It was thought that this alteration might affect cognitive functions because hippocampal NMDA receptors are involved in the memory and learning processes. Melatonin exhibited a partially protective effect on NR2A and NR2B against OTA.     

Pinealectomy Does Not Affect the Healing of Experimental Colonic Anastomoses

Gastrointestinal system anastomoses, especially colonic anastomoses, have significant morbidity and mortality despite recent technical improvements. Besides regulating the circadian rhythm, the pineal gland and its main neurohormone product melatonin have widespread actions in the organism. The purpose of this study was to investigate the effects of pinealectomy on the healing of colonic anastomoses. One hundred male albino Wistar rats were used in this study. The rats were separated into three groups: control, pinealectomy, and sham groups. In the control group, only colonic resection and anastomoses were performed. Following pinealectomy, colonic anastomosis was performed 2 weeks later on one half and 2 months later on the other half of the pinealectomy group. Only craniotomy was performed on the sham group, and the rats were separated and evaluated like the pinealectomy group. Colonic anastomoses were evaluated on postanastomotic day 3 and 7 by measuring the bursting pressure and the hydroxyproline levels in the anastomotic segments. There was no difference in the bursting pressure measurements between the groups on both postoperative day 3 and 7. Although hydroxyproline levels were different between groups on both postanastomotic days 3 and 7, it has been observed that neither normal nor anastomotic hydroxyproline levels influenced the anastomotic bursting pressure measurements. The percent deviation from the normal values was compared in the anastomotic segments, and no differences were found regarding the bursting pressure and hydroxyproline levels. It was concluded that pinealectomy has no effect on the healing of colonic anastomoses.     

Maxillary molar distalization with a bone-anchored pendulum appliance

To obtain an effective and compliance-free molar distalization without an anchorage loss, we designed the bone-anchored pendulum appliance (BAPA). The aim of this study was to evaluate the stability of the anchoring screw, distalization of the maxillary molars, and the movement of teeth anterior to maxillary first molars. The study group comprised 10 patients (mean age 13.5 +/- 1.8 years) with Class II molar relationship. A conventional pendulum appliance was modified to obtain anchorage from an intraosseous screw instead of the premolars. The screw was placed in the anterior paramedian region of the median palatal suture. Skeletal and dental changes were measured on cephalograms, and dental casts were obtained before and after distalization. A super Class I molar relationship was achieved in a mean period of 7.0 +/- 1.8 months. The maxillary first molars distalized an average of 6.4 +/- 1.3 mm in the region of the dental crown by tipping distally an average of 10.9 degrees +/- 2.8 degrees . Also, the maxillary second premolar and first premolar moved distally an average of 5.4 +/- 1.3 mm and 3.8 +/- 1.1 mm, respectively. The premolars tipped significantly distally. No anterior incisor movement was detected. The BAPA was found to be an effective, minimally invasive, and compliance-free intraoral distalization appliance for achieving both molar and premolar distalization without any anchorage loss.     

Antimicrobial properties of self-etching primer-bonding systems

Self-etching primers are now considered the new generation of dentin bonding systems that modify and incorporate the bacteria-containing smear layer into their bonding mechanism. The antibacterial effects of the self-etching primers Clearfil SE Bond, Mac Bond, Imperva FL Bond, One-Up BondF and Prompt L-Pop were evaluated using the bacteria Streptococcus mutans ATCC25175, Peptostreptococcus anaerobius, Peptostreptococcus prevotii, Peptostreptococcus asaccharolyticus, Lactobacillus acidophilus, Lactobacillus catenaforme, Lactobacillus jensenii, Actinomyces odontolyticus, Porphyromonas endodontalis, Clostridium ramosum, Prevotella oris, Prevotella denticola and Fusobacterium nucleatum, with a disk diffusion method. A single-bottle total-etch dentin adhesive (Excite) was used for comparisons and chlorhexidine (0.2%) was used as the positive control. After incubation, zones of inhibited bacterial growth were observed. One-Up BondF, Prompt L-Pop and Excite showed growth inhibition for all bacterial strains. The bonding agents of Clearfil SE Bond, Mac Bond and Imperva FL Bond were unable to inhibit the growth of Lactobacillus jensenii and Actinomyces odontolyticus, while the primers of these systems produced inhibition halos to all tested microorganisms greater than that of chlorhexidine.     

Ablation of XP-V gene causes adipose tissue senescence and metabolic abnormalities

Obesity and the metabolic syndrome have evolved to be major health issues throughout the world. Whether loss of genome integrity contributes to this epidemic is an open question. DNA polymerase η (pol η), encoded by the xeroderma pigmentosum (XP-V) gene, plays an essential role in preventing cutaneous cancer caused by UV radiation-induced DNA damage. Herein, we demonstrate that pol η deficiency in mice (pol η^−/−) causes obesity with visceral fat accumulation, hepatic steatosis, hyperleptinemia, hyperinsulinemia, and glucose intolerance. In comparison to WT mice, adipose tissue from pol η^−/− mice exhibits increased DNA damage and a greater DNA damage response, indicated by up-regulation and/or phosphorylation of ataxia telangiectasia mutated (ATM), phosphorylated H₂AX (γH₂AX), and poly[ADP-ribose] polymerase 1 (PARP-1). Concomitantly, increased cellular senescence in the adipose tissue from pol η^−/− mice was observed and measured by up-regulation of senescence markers, including p53, p16^Ink4a, p21, senescence-associated (SA) β-gal activity, and SA secretion of proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) as early as 4 wk of age. Treatment of pol η^−/− mice with a p53 inhibitor, pifithrin-α, reduced adipocyte senescence and attenuated the metabolic abnormalities. Furthermore, elevation of adipocyte DNA damage with a high-fat diet or sodium arsenite exacerbated adipocyte senescence and metabolic abnormalities in pol η^−/− mice. In contrast, reduction of adipose DNA damage with N-acetylcysteine or metformin ameliorated cellular senescence and metabolic abnormalities. These studies indicate that elevated DNA damage is a root cause of adipocyte senescence, which plays a determining role in the development of obesity and insulin resistance.The human genome is constantly challenged by exogenous and endogenous DNA damaging agents. To ensure genome integrity, human cells have faithful DNA replication machinery and DNA repair systems that are coordinated by DNA damage response networks. In response to different extents or types of DNA lesions, the DNA damage response activates appropriate cellular responses, including transient or permanent (senescence) cell cycle arrest, or apoptosis, to minimize the detrimental effects of DNA lesions (1). Reduction or deficiency in DNA repair/replication enzyme activity is well documented to increase vulnerability for the development of cancer, neurodegenerative diseases, and aging (2). In addition, defective DNA repair enzymes are associated with the metabolic symptom; for example, DNA glycosylase (Neil1)- and OGG1-deficient mice are obese (3–5), and nucleotide excision repair protein ERCC1-XPF deficiency causes lipodystrophy (6). Furthermore, DNA damage response protein ataxia telangiectasia mutated (ATM) suppresses JNK activity through p53 signaling and mediates an antioxidant action that has been suggested to be relevant to the metabolic syndrome (7). Nucleotide excision repair XP-A protein may affect metabolism by altering mitochondrial function (8). To date, the mechanisms that link genome instability and metabolic dysregulation have not been elucidated.DNA polymerase η (pol η) is a specialized lesion bypass polymerase that faithfully replicates across UV-induced cyclobutane pyrimidine dimers (9) to rescue stalled DNA replication forks from potential breakages and mutations. Defects in the gene encoding pol η produce a variant form of the autosomal recessive disease xeroderma pigmentosum (XP-V) (9). Patients with XP-V are highly sensitive to sunlight and prone to cutaneous cancer (9). In addition to skin, pol η is expressed in most tissues (10). The expression of pol η correlates with the effectiveness of anticancer therapeutic agents that exert their activity by introducing DNA lesions that block the progression of DNA replication (11). In addition to exogenous introduced DNA lesions, pol η contributes to genomic stability during unperturbed DNA replication (12) and replicates across reactive oxygen species (ROS)-induced oxidative DNA lesions 8-oxoG (7,8-dihydro-8-oxoguanine), thymine glycol, and lipid peroxidation DNA adducts generated during endogenous metabolic processes (13, 14). ROS generated from endogenous metabolism or exogenous sources has been associated with cancer, aging, and the metabolic syndrome.Therefore, the initial hypothesis for our studies was that pol η contributes to reduce tumorigenesis by managing oxidative DNA lesions in other organs. However, in a 2-y study, no increase in the incidence of tumors of any type was found with pol η KO (pol η^−/−) mice (15). Instead, we found pol η^−/− mice develop metabolic abnormalities that induce obesity.     

Antifungal susceptibilities of dermatophytic agents isolated from clinical specimens

The aim of this study was to investigate the susceptibility to four antifungal agents: ketoconazole, terbinafine, itraconazole and fluconazole, of the different species of dermatophyte strains isolated from clinical specimens. A total of 128 specimens were collected from toe nail, foot, inguinal region, trunk, hands and head. The dermatophytes tested included Trichophyton rubrum 108 (84.4%), Trichophyton mentagrophytes 11 (8.6%), Epidermophyton floccosum 5 (3.9%), Microsporum canis 2 (1.5%) and Trichophyton tonsurans 2 (1.5%). The mean minimum inhibitory concentrations (MIC) for the five species of dermatophytes ranged between 0.09-1.12 microg/mL for ketoconazole, 0.04-0.27 microg/mL for terbinafine, 0.08-0.43 microg/mL for itraconazole and 16.18-24.0 microg/mL for fluconazole. In vitro analysis of antifungal activity of these agents would also allow for the comparison between different systemic antifungals, which in turn may clarify the reasons for the lack of clinical response or serve as an effective therapy for patients with chronic infection.