Metabolism of Acetaminophen by Enteric Epithelial Cells Mitigates Hepatocellular Toxicity In Vitro.

The gut-liver axis is defined by dietary and environmental communication between the gut, microbiome and the liver with its redox and immune systems, the overactivation of which can lead to hepatic injury. We used media preconditioning to mimic some aspects of the enterohepatic circulation by treating the human Caco-2 intestinal epithelial cell line with 5, 10 and 20 mM paracetamol (N-acetyl-para-aminophenol; APAP) for 24 h, after which cell culture supernatants were transferred to differentiated human hepatic HepaRG cells for a further 24 h. Cell viability was assessed by mitochondrial function and ATP production, while membrane integrity was monitored by cellular-based impedance. Metabolism by Caco-2 cells was determined by liquid chromatography with tandem mass spectrometry. Caco-2 cell viability was not affected by APAP, while cell membrane integrity and tight junctions were maintained and became tighter with increasing APAP concentrations, suggesting a reduction in the permeability of the intestinal epithelium. During 24 h incubation, Caco-2 cells metabolised 64-68% of APAP, leaving 32-36% of intact starting compound to be transferred to HepaRG cells. When cultured with Caco-2-preconditioned medium, HepaRG cells also showed no loss of cell viability or membrane integrity, completely in contrast to direct treatment with APAP, which resulted in a rapid loss of cell viability and membrane integrity and, ultimately, cell death. Thus, the pre-metabolism of APAP could mitigate previously observed hepatotoxicity to hepatic tight junctions caused by direct exposure to APAP. These observations could have important implications for the direct exposure of hepatic parenchyma to APAP, administered via the intravenous route.

Does onlay mesh placement in emergency laparotomy prevent incisional hernia? A prospective randomized double-blind study.

PURPOSE: The objective of this study is to assess the effectiveness and safety of onlay mesh closure of emergency midline laparotomy to prevent incisional hernia. METHODS: This is a prospective randomized double-blind study and was carried out in the General Surgery Clinic, Konya City Hospital, from August 1, 2020 to August, 1, 2021. The study included 108 patients who were randomly grouped in 2 groups: patients with conventional abdominal closure and closure using additional onlay mesh (1:1). The follow-up period was for a year. The primary outcome was the incidence of incisional hernia and secondary outcomes were clinical data like complications, hospital length of stay, re-operations. RESULTS: It was observed that incisional hernia was present in 14 patients (27.4%) in conventional abdominal closure group and was in 2 patients using mesh (4%), (p = 0.001). Clavien-Dindo 3B complications were in rise in conventional closure group (p = 0.02). Of all complications, burst abdomen was significantly more common in conventional closure group (p = 0.04). The rate of surgically treated complications were higher in conventional closure group (p = 0.02). Clavien-Dindo 3A complications were more common in patients with contaminated wound in mesh group (p = 0.02). CONCLUSION: The use of mesh while closing the abdomen in emergency midline laparotomy reduces the risk of incisional hernia. Thus, to lower the risks of incisional hernia and its complications, prophylactic mesh can be used in high-risk patients.

Effect on oxidative stress, hepatic chemical metabolizing parameters, and genotoxic damage of mad honey intake in rats.

A total of 66 male Wistar rats were used and six groups (control: 10 animals and experimental: 12 animals) were formed. While a separate control group was established for each study period, mad honey application to the animals in the experimental group was carried out with a single dose (12.5 g kg-1 body weight (b.w.); acute stage), at a dose of 7.5 g kg-1 b.w. for 21 days (subacute stage), and at a dose of 5 g kg-1 b.w. for 60 days (chronic stage). Tissue and blood oxidative stress markers (malondialdehyde (MDA), nitric oxide (NO), 4-hydroxynonenal (HNE), superoxide dismutase, catalase, glutathione (GSH) peroxidase, and glucose-6-phosphate dehydrogenase), hepatic chemical metabolizing parameters in the liver (cytochrome P450 2E1, nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase, nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase (CYTC), GSH S-transferase (GST), and GSH), and micronucleus and comet test in some samples were examined. Findings from the study showed that single and repeated doses given over the period increased MDA, NO, and HNE levels while decreasing/increasing tissue and blood antioxidant enzyme activities. From hepatic chemical metabolizing parameters, GST activity increased in the subacute and chronic stages and CYTC activity increased in the acute period, whereas GSH level decreased in the subacute stage. Changes in tail and head intensities were found in most of the comet results. Mad honey caused oxidative stresses for each exposure period and made some significant changes on the comet test in certain periods for some samples obtained. In other words, according to the available research results obtained, careless consumption of mad honey for different medical purposes is not appropriate.

Pullout performance comparison of pedicle screws based on cement application and design parameters.

Pedicle screws are the main fixation devices for certain surgeries. Pedicle screw loosening is a common problem especially for osteoporotic incidents. Cannulated screws with cement augmentation are widely used for that kind of cases. Dual lead dual cored pedicle screw has already given promising pullout values without augmentation. This study concentrates on the usage of dual lead dual core with cement augmentation as an alternative to cannulated and standard pedicle screws with cement augmentation. Five groups (dual lead dual core, normal pedicle screw and cannulated pedicle screw with augmentation, normal pedicle screw, dual lead dual cored pedicle screw) were designed for this study. Healthy bovine vertebrae and synthetic polyurethane foams (grade 20) were used as embedding test medium. Test samples were prepared in accordance with surgical guidelines and ASTM F543 standard testing protocols. Pullout tests were conducted with Instron 3300 testing frame. Load versus displacement values were recorded and maximum pullout loads were stated. The dual lead dual cored pedicle screw with poly-methyl methacrylate augmentation exhibited the highest pullout values, while dual lead dual cored pedicle screw demonstrated similar pullout strength as cannulated pedicle screw and normal pedicle screw with poly-methyl methacrylate augmentation. The dual lead dual cored pedicle screw with poly-methyl methacrylate augmentation can be used for osteoporotic and/or severe osteoporotic patients according to its promising results on animal cadaver and synthetic foams.

Minimally invasive preperitoneal single-layer mesh repair versus standard Lichtenstein hernia repair for inguinal hernia: a prospective randomized trial.

PURPOSE: To compare a minimally invasive preperitoneal (MIP) single-layer mesh repair with the standard Lichtenstein hernia repair (LHR) for inguinal hernia in terms of operative characteristics, recovery, complications, recurrence and chronic pain. METHOD: Two hundred and twenty male patients diagnosed with primary inguinal hernia were randomized to either MIP or LHR methods. MIP repair consisted of a single-layer polypropylene mesh developed by our group placed preperitoneally using the Kugel technique. Patients were followed for a minimum of 2 years. Chronic pain was assessed by Sheffield's pain score. RESULTS: One hundred and one patients in MIP group and 105 patients in LHR group were included in the analysis. Most patients were diagnosed with indirect hernia (n = 79 for MIP, n = 81 for LHR). Surgery was slightly but significantly shorter for MIP (38.2 ± 7.4 vs. 40.3 ± 6.6, p = 0.031). Early complications such as cord edema, hematoma, scrotal edema, and wound infection were infrequent in both groups. Recurrence was detected in three patients in MIP and one patient in LHR. Chronic pain score was similar with both methods within the first year, but significantly lower for MIP at 24 months (0.66 ± 0.06 vs. 0.87 ± 0.07, p = 0.03). CONCLUSION: MIP single-layer mesh repair is as effective and safe as LHR, with the additional benefits of minimally invasive nature, less chronic pain at 2 years and low polypropylene load when compared with the original Kugel patch.

INVESTIGATION OF STAT5A, FSHR AND LHR GENE POLYMORPHISMS IN TURKISH INDIGENOUS CATTLE BREEDS (EAST ANATOLLAN RED, SOUTH ANATOLIAN RED, TURKISH GREY, ANATOLIAN BLACK AND ZAVOT).

The objective of this study was to examine the allelic and genotypic profiles of the Signal Transducer and Activator of Transcription 5A (STAT5A), Follicle Stimulating Hormone Receptors (FSHR), and Luteinizing Hormone Receptor (LHR) genes in five indigenous cattle breeds in Turkey. For this purpose, a total of 329 cattle from East Anatolian Red (EAR), South Anatolian Red (SAR), Turkish Grey (TG), Anatolian Black (AB), and Zavot were genotyped using by PCR-RFLP method. A215 bp fragment of STAT5A, a 306bp fragment of FSHR, and a 303 bp fragment of LHR were amplified and digested with AvaI, AluI, and HhaI restriction enzymes, respectively. In this study two types of alleles C and Tfor STAT5A, C and G for FSHR and C and T for LHR were observed. The highest frequencies for STAT5A-C and STAT5A-T alleles were estimated for the Zavot and TG breeds (0.86) and the EAR breed (0.29), respectively. The highest frequency for FSHR-C and FSHR-G alleles was estimated for the Zavot breed (0.72) and the AB and SARbreeds (0.35), respectively. The highest frequency for LHR-C and LHR-T alleles was estimated for the EAR breed (0.75) and the AB breed (0.39), respectively. According to FT values, a small level of genetic diversity was found among five cattle breeds. The F(ST) value was calculated 0.019 between AB and Zavot. And, the value was significant (p < 0.001), while the other F(ST) values were not significant. According to the genetic distance values (Nei), the highest genetic distance was found between AB and TG while the smallest genetic distance was found between Zavot and TG. The chi-square test showed that the TG and Zavot breeds were in Hardy-Weinberg equilibrium (HWE) for STAT5A gene; the EAR, SAR, TG, and Zavot breeds were in HWE for FSHR gene and the EAR, SAR, and TG breeds were in HWE for LHR gene. In conclusion, further investigation is required to determine the correlation of the FSHR and LHR genes with early puberty for the improvement of sexual precocity, and it is considered that the STAT5A gene may be used to improve the milk yield and milk yield traits of local cattle breeds, including those indigenous to Turkey.

Genotoxic effects of some antituberculosis drugs and mixtures in rats.

In this study*, it was aimed to observe, genotoxic effects of antituberculosis drugs and combinations on rats. Animals were treated with 31.5 mg/kg isoniazid (INH), 54 mg/kg rifampicin (RIF), 189 mg/kg pyrazinamide (PYR), 100 mg/kg etham-butol(ETA), INH+RIF+PYR (MIX1) and INH+RIF+PYR+ETA (MIX2) mixtures applied via gavage for 90 days. At the end of the study, blood, liver and kidney samples were taken and evaluated by Comet and Micronucleus techniques. Compared to control group, head intensity decreased, tail intensity and tail migration increased on experiment groups in blood samples. Head intensity of PYR and mixture groups decreased, tail intensity of PYR and mixture groups increased and tail migration of PYR, ETA and mixture groups increased in liver samples. Head intensity decreased and tail intensity increased of INH, RIF, ETA and MIX1 group; tail migration increased of MIX1 group in kidney samples. Compared to control group, micronucleus rate of ETA, RIF and MIX 2 groups increased in experiment groups. In conclusion antituberculosis drugs and their mixtures applied for 90 days causes to double strand break of DNA damage at different degrees in blood, kidney and liver cells in rats.

Which flap method should be preferred for the treatment of pilonidal sinus? A prospective randomized study.

BACKGROUND: Although many methods, either surgical or non-surgical, are being used for the treatment of pilonidal sinus disease (PSD), there is still no consensus as to what constitutes the most appropriate method of treatment. The aim of this study was to compare the outcomes of the Limberg flap (LF), modified Limberg flap (MLF), and Karydakis flap (KF) procedures. METHODS: A prospective, randomized study was conducted on 295 patients scheduled for surgical treatment for PSD at the General Surgery Clinic of the Konya Training and Research Hospital in January 2009-May 2010. Patients with recurrent disease, an ASA score higher than III, obesity (BMI > 35 kg/m(2)), insulin-dependent diabetes, or a drug or alcohol addiction were excluded. The procedures performed were as follows: LF (n = 96), MLF (n = 108), and KF (n = 91). RESULTS: The patients were followed up for a median of 33 months (range 24-41 months). There were more female patients in the LF group. The rate of seroma formation was higher in the KF group (19.8 %) compared to the LF and MLF groups (5.2 and 7.4 %, respectively; p = 0.027). The rate of wound dehiscence was higher in the KF group (15.4 %) compared to the LF and MLF groups (2.1 and 3.7 %, respectively; p < 0.001) as was the incidence of flap maceration (11 % in the KF vs. 1 % in the LF and 3.7 % in the MLF; p = 0.004). The incidence of PSD recurrence was also higher in the KF group (11 %) compared to the LF and MLF groups (6.3 and 1.9 % respectively; p = 0.027). In a multivariate analysis, the presence of seroma, hematoma, and wound infection were independent predictors of recurrence. CONCLUSIONS: In our study, LF and MLF procedures were associated with a lower recurrence and complication rate compared to KF. However, more randomized studies comparing different reconstruction methods after PSD excision are needed.

Postfusion pullout strength comparison of a novel pedicle screw with classical pedicle screws on synthetic foams.

Pullout is a very common failure mode on the use of pedicle screws. Numerous studies were completed to increase the pullout strength of pedicle screws especially for osteoporotic bones. In this study, a previously designed pedicle screw type was tested before and after fusion condition. Synthetic polyurethane foams were used in all tests. Three different grades of foams were used in tests to simulate severely osteoporotic, osteoporotic, and healthy bones. Test blocks were produced and characterized in our clinical biomechanics laboratory. Foaming of polyurethane was accepted as fusion process (bone in growth). Pedicle screw including radial holes (new design) was tested both before and after the fusion. It also exhibited remarkably higher pullout strength after fusion than before fusion and most of other alternatives stated in the literature. In total, 70% higher pullout strength was achieved with new design after fusion. On the other hand, new design did not dominate other alternatives when comparison was carried out on severely osteoporotic and healthy bones. To the knowledge of the authors, this is the first study investigating the postfusion properties on synthetic foams.

Effect of chronic anal fissure components on isosorbide dinitrate treatment.

BACKGROUND: Chronic anal fissure is diagnosed in the presence of persistent symptoms: The classic triad includes a linear mucosal tear exposing the internal sphincter fibers, hypertrophied anal papilla, and a sentinel skin tag. Thus, chronic anal fissure can be divided into three components: the fissure itself; hypertrophied anal papilla; the sentinel skin tag. Not every chronic anal fissure has all three components; some have two components, and others present with only a persistent fissure. The success rate of medical treatment for chronic anal fissure is reported as 42-86 %. In this study, we intended to observe the effect of said components on healing with isosorbide dinitrate treatment. METHODS: A total of 105 patients with chronic anal fissures were admitted and were divided into three groups. Patients in group I had a single component (only the fissure with a linear mucosal tear exposing the internal sphincter fibers); group II had two components (skin tag or hypertrophied papilla in addition to the fissure); group III had all three components (fissure, skin tag, hypertrophied papilla). Isosorbide dinitrate 0.25 % was applied three times a day. RESULTS: The success rates in the study groups were 93, 74, and 64 %, respectively. The success rate was significantly higher for group I than for groups II and III. CONCLUSIONS: Chronic anal fissure components should be considered when evaluating the success rates of studies reporting the results of various medical treatments. The number of components seems to be an important factor that affects the results of isosorbide dinitrate treatment.

A case with a rare chromosomal abnormality: isochromosome 18p.

Isochromosome 18p (i(18p)), is a rare chromosomal disorder that occurs once in about every 140,000 live births and affects males and females equally. Most of the cases are due to a de novo formation but in the literature familial cases were reported. Here, we report a young female with dysmorphic features as microcephaly, frontal bossing, strabismus, low-set ears, small pinched up nose, small mouth, high palate and long philtrum, presenting a small metacentric chromosome. Besides the dysmorphic features she also has gastroesophageal reflux, spasticity, strabismus and specific brain MRI findings as dilatation of the right lateral ventricle trigonum occipital horn (colpocephaly), thinning of the corpus callosum especially of the posterior part and abnormality of the white matter myelinisation at the frontal and occipital region. Particularly the MR findings are rarely reported in the literature.

Prevention of intraabdominal adhesions produced by polypropylene mesh.

Polypropylene mesh (PPM) is widely used in ventral hernia repair, however is also associated with visceral adhesions when the mesh is exposed to intraabdominal organs. In this study, a composite mesh [ePTFE (expanded polytetrafluoroehylene) + PPM] and sodium hyaluronate/carboxymethyl cellulose (NaHA/CMC) membrane laid under PPM are evaluated in terms of adhesion formation in a rat model of ventral hernia repair. In this experimental study, a 2 x 1 cm of peritoneum and underlying muscle defect was created at the right side of the anterior abdominal wall of 37 male Wistar albino rats. These defects were repaired with 2.5 x 2 cm PPM in group 1 (n = 13), with composite mesh in group 2 (n = 12) and with PPM+NaHA/CMC in group 3 (n = 12). Rats were sacrificed after 14 days and the prosthetic materials were examined for the calculation of surface area percentage covered by adhesions, for organ involvement in the adhesions and for histological evaluation. There was a reduction in the adhesion-covered area in group 2 and group 3. Organ involvement was predominantly seen in group 1. Neoperitoneum was perfect in group 2. Fibrosis and inflammation were higher in group 1. All groups showed adhesiogenic potential to some extent. This potential was maximum with PPM. Both ePTFE and NaHA/CMC displayed similar effects in preventing adhesion formation.

A mathematical model of the ascending colon of the horse.

In this study we present a geometric model of the ascending colon of the horse, especially the left ventral colon and the right ventral colon, the left dorsal colon and the right dorsal colon and the pelvic flexure. We also present a mathematical model of the cross sections of these ascending colon parts with the exceptions of the pelvic flexure. We show that these cross-sections correspond to the closed algebraic curves known as epitrochoid.

A geometric description of the ascending colon of some domestic animals.

In this study, a geometric recognition of the ascending colons of some domestic animals such as pig, ruminants (only the ansa spiralis coli) and dog is presented. The ascending colon of these animals can be considered a tubular shape along a special curve.

Sex differences in dog corpus callosum.

Human studies reported sex differences in size and shape of the corpus callosum. These observations have been contested. The purpose of the present study is to investigate possible sex differences in the corpus callosum of dogs. The entire brains including the medulla from 12 female and 9 male adult mongrel dogs were removed and weighed. Total and partial area measurements of the callosum were made from photographic tracings of its outline. The callosum was partitioned into 3 regions; anterior half, posterior half, posterior one-fifth. The total corpus callosum, anterior half, posterior half, and posterior fifth or splenium areas were measured. Sex differences were found. The anterior half, the posterior half, the posterior fifth, and the total callosum were significantly greater in absolute area in males than in females.