ABSTRACT
There have been few objective evaluations of the effects of deep neuromuscular blockade on intra-operative conditions. In this prospective randomised controlled study, we evaluated the effects of deep neuromuscular block on surgical conditions during laparoscopic colorectal surgery. Patients were randomly allocated using a computer-generated randomisation code to either moderate (train-of-four count 1-2 maintained and antagonised with neostigmine) or deep (post-tetanic count 1-2 maintained and reversed with sugammadex) levels of neuromuscular blockade. The primary outcome measure was the number of abrupt increases in intra-abdominal pressure intra-operatively. Secondary outcome variables were intra-operative restoration of spontaneous breathing, number of surgical requests for additional neuromuscular blockade, surgical rating of operating conditions and patient satisfaction. The surgeon who rated the surgical conditions score and investigator who checked the postoperative variables were blinded to patient allocation. In total, we recruited 70 patients of whom 64 (32 in each group) were analysed. Increases in intra-abdominal pressure (14/32 vs. 6/32; p = 0.031), intra-operative restoration of spontaneous breathing (16/32 vs. 2/32; p < 0.001) and request for additional neuromuscular blockade (21/32 vs. 8/32; p = 0.001) were more frequent in the moderate compared with the deep group. In patients undergoing elective laparoscopic colorectal surgery, deep neuromuscular blockade provided better surgical conditions than moderate neuromuscular blockade, as measured by a reduction in the incidence of intra-abdominal pressure alarms.
Subject(s)
Colorectal Neoplasms/surgery , Laparoscopy/methods , Neuromuscular Blockade/methods , Adult , Aged , Double-Blind Method , Drug Administration Schedule , Female , Humans , Intraoperative Period , Male , Middle Aged , Monitoring, Intraoperative/methods , Neuromuscular Nondepolarizing Agents/administration & dosage , Patient Satisfaction , Pneumoperitoneum, Artificial , Prospective Studies , Rocuronium/administration & dosage , Young AdultABSTRACT
Some short procedures require deep neuromuscular blockade, which needs to be reversed at the end of the procedure. Forty-four patients undergoing elective laryngeal micro-surgery were randomly allocated into two groups: rocuronium 0.45 mg.kg-1 with neostigmine (50 µg.kg-1 with glycopyrrolate 10 µg.kg-1 ) reversal (moderate block group) vs. rocuronium 0.90 mg.kg-1 with sugammadex (4 mg.kg-1 ) reversal (deep block group). The primary outcome was the intubating conditions during laryngoscopy secondary outcomes included recovery of neuromuscular block; conditions for tracheal intubation; satisfaction score as determined by the surgeon; onset of neuromuscular block; and postoperative sore throat. The onset of neuromuscular block was more rapid, and intubation conditions and ease of intra-operative laryngoscopy were more favourable, and the satisfaction score was lower in the moderate block group compared with the deep block group. No difference was found in the incidence of postoperative sore throat. In laryngeal micro-surgery, the use of rocuronium 0.9 mg.kg-1 with sugammadex for reversal was associated with better surgical conditions and a shorter recovery time than rocuronium 0.45 mg.kg-1 with neostigmine.
Subject(s)
Neostigmine/pharmacology , Neuromuscular Blockade/methods , Neuromuscular Nondepolarizing Agents/antagonists & inhibitors , Rocuronium/antagonists & inhibitors , Sugammadex/pharmacology , Adult , Aged , Anesthesia Recovery Period , Anesthesia, General/methods , Attitude of Health Personnel , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Intubation, Intratracheal/adverse effects , Intubation, Intratracheal/methods , Laryngoscopy/adverse effects , Laryngoscopy/methods , Larynx/surgery , Male , Microsurgery , Middle Aged , Neuromuscular Nondepolarizing Agents/administration & dosage , Pharyngitis/etiology , Postoperative Complications , Rocuronium/administration & dosageABSTRACT
The objective of this study was to evaluate the present conventional selection program of a swine nucleus farm and compare it with a new selection strategy employing genomic enhanced breeding value (GEBV) as the selection criteria. The ZPLAN+ software was employed to calculate and compare the genetic gain, total cost, return and profit of each selection strategy. The first strategy reflected the current conventional breeding program, which was a progeny test system (CS). The second strategy was a selection scheme based strictly on genomic information (GS1). The third scenario was the same as GS1, but the selection by GEBV was further supplemented by the performance test (GS2). The last scenario was a mixture of genomic information and progeny tests (GS3). The results showed that the accuracy of the selection index of young boars of GS1 was 26% higher than that of CS. On the other hand, both GS2 and GS3 gave 31% higher accuracy than CS for young boars. The annual monetary genetic gain of GS1, GS2 and GS3 was 10%, 12%, and 11% higher, respectively, than that of CS. As expected, the discounted costs of genomic selection strategies were higher than those of CS. The costs of GS1, GS2 and GS3 were 35%, 73%, and 89% higher than those of CS, respectively, assuming a genotyping cost of $120. As a result, the discounted profit per animal of GS1 and GS2 was 8% and 2% higher, respectively, than that of CS while GS3 was 6% lower. Comparison among genomic breeding scenarios revealed that GS1 was more profitable than GS2 and GS3. The genomic selection schemes, especially GS1 and GS2, were clearly superior to the conventional scheme in terms of monetary genetic gain and profit.
ABSTRACT
We examined the use of neostigmine for reversing shallow (defined as train-of-four ratio of 0.5), cisatracurium- and rocuronium-induced neuromuscular block in 112 patients, by use of 0 µg.kg(-1) , 10 µg.kg(-1) , 20 µg.kg(-1) or 40 µg.kg(-1) dose of neostigmine for reversal. The times from neostigmine administration to train-of-four ratios of 0.7, 0.9 and 1.0 were evaluated. Analysis of variance showed that the duration of action was significantly longer after cisatracurium compared with rocuronium. The time to reach a train-of-four ratio of 1.0 was significantly shorter with neostigmine 40 µg.kg(-1) compared with lower neostigmine doses, and at this dose the time did not differ between cisatracurium and rocuronium. The recovery time from a train-of-four ratio of 0.5-1.0 did not differ between cisatracurium and rocuronium, and was significantly shortened by the administration of neostigmine. We conclude that a neostigmine dose of 40 µg.kg(-1) was the most effective at reducing recovery time after neuromuscular blockade.
Subject(s)
Androstanols/antagonists & inhibitors , Anesthesia Recovery Period , Atracurium/analogs & derivatives , Cholinesterase Inhibitors/pharmacology , Neostigmine/pharmacology , Neuromuscular Blockade , Analysis of Variance , Atracurium/antagonists & inhibitors , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Neuromuscular Blocking Agents/antagonists & inhibitors , Neuromuscular Nondepolarizing Agents/antagonists & inhibitors , Rocuronium , Time FactorsABSTRACT
The efficacy of preoperative autologous blood donation (PABD) was evaluated according to preoperative haemoglobin (Hb) values. The records of 295 patients who underwent bimaxillary orthognathic surgery between July 2007 and August 2008 were reviewed. The records for autologous blood donation, intraoperative transfusion, and related laboratory studies were also evaluated. The transfusion trigger used during this period was Hb < 10 g/dl. A total of 189 patients (64.1%) made a PABD and 106 patients (35.9%) did not. The incidence of allogeneic blood transfusion was significantly lower in the PABD group than in the no PABD group (15.9% vs. 29.2%, P = 0.007). This difference was greater in patients with a preoperative Hb < 14 g/dl (20.3% vs. 62.5%, P < 0.0001), and no difference was found in patients with Hb ≥ 14 g/dl (13.3% vs. 14.9%, P = 0.83). PABD reduced the incidence of allogeneic blood transfusion in patients undergoing bimaxillary orthognathic surgery, particularly in patients with a preoperative Hb < 14 g/dl. PABD could be used to reduce the frequency of intraoperative allogeneic blood transfusion in these patients.
Subject(s)
Blood Donors , Blood Transfusion, Autologous/statistics & numerical data , Orthognathic Surgery/methods , Preoperative Period , Adolescent , Adult , Aged , Female , Humans , Male , Maxilla/surgery , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
After elective ear surgery with cisatracurium neuromuscular blockade, 48 adults were randomly assigned to receive neostigmine: (a) at appearance of the fourth twitch of a 'train-of-four'; (b) at loss of fade to train-of-four; or (c) at loss of fade to double-burst stimulation, all monitored using a TOF-Watch SX® on one arm. For each of these conditions, the recovery from train-of-four (TOF) ratio was measured in parallel objectively using a TOF-Watch SX placed on the contralateral arm. The median (IQR [range]) time from administration of reversal to a train-of-four ratio ≥ 0.9 was 11 (9-15.5 [2-28]) min, 8 (4-13.5 [1-25]) min and 7 (4-10 [2-15]) min in the three groups, respectively. This recovery time was significantly shorter when reversal was given at loss of fade to double-burst stimulation (c), than when given at the appearance of the fourth twitch (a), p = 0.046. However, the total time to extubation may be unaffected as it takes longer for fade to be lost after double-burst stimulation than for four twitches subjectively to appear.
Subject(s)
Anesthesia Recovery Period , Atracurium/analogs & derivatives , Electric Stimulation , Neostigmine/administration & dosage , Neuromuscular Blockade/methods , Cholinesterase Inhibitors/administration & dosage , Drug Administration Schedule , Ear/innervation , Ear/surgery , Female , Humans , Male , Middle Aged , Neuromuscular Blocking Agents , Neuromuscular Junction/drug effects , Time FactorsABSTRACT
This study was conducted to estimate the genetic parameters for pork belly traits and muscles in Yorkshire pigs. Each pork belly was cut into nine parts perpendicular to the thoracic vertebrae (6th to 14th). Traits of belly muscles including the deep pectoral, latissimus dorsi, cutaneous trunci, rectus abdominis, external and internal abdominal oblique from 382 purebred pigs were recorded and analyzed using SAS Package (9.1) and Derivative-free restricted maximum likelihood methods. Heritability estimates for belly traits ranged from 0.27 to 0.49, while they were 0.12 to 0.66 for belly muscles. Moderate to high heritability estimates were noted in belly weight (0.33), belly length (0.28), and belly width (0.49). In belly muscles, the latissimus dorsi and deep pectoral, which are located only in the 6th to 9th vertebrae sections, were found to have heritability estimates ranging from 0.21 to 0.29 and 0.23 to 0.35, respectively. Strong heritability estimates were observed in the 7th to 13th sections of cutaneous trunci muscle ranging from 0.42 to 0.66. Genetic correlations of latissimus dorsi m. with belly length were positive (0.50), while cutaneous trunci m. with belly weight also revealed a positive relationship that ranged from 0.35 to 0.47. The estimated genetic parameters indicate that belly weight can be improved by genetic selection. Differences in the levels of heritability occurred among various parameters of Yorkshire pork belly, which should be considered when performing selection to improve pork belly quality. Moreover, these results can provide valuable information that can be used as the basis for further investigations to improve pork belly.
ABSTRACT
This experiment was conducted to investigate the effects of palm kernel expellers on growth performance, nutrient digestibility, and blood profiles of weaned pigs. A total of 88 weaned pigs (6.94±0.76 kg body weight [BW]; 28 d old) were randomly allotted to 2 dietary treatments (4 pigs/pen; 11 replicates/treatment) in a randomized complete block design (sex as a block). The dietary treatments were a typical nursery diet based on corn and soybean meal (CON) and CON added with 20% of palm kernel expellers (PKE). Pigs were fed for 6 wk using a 3-phase feeding program with declining diet complexity and with phases of 1, 2, and 3 wk, respectively. Blood was collected from randomly selected 2 pigs in each pen before weaning and on d 7 after weaning. Pigs were fed respective dietary treatments containing 0.2% chromic oxide from d 29 to 35 after weaning. Fecal samples were collected from randomly selected 2 pigs in each pen daily for the last 3 days after the 4-d adjustment period. Measurements were growth performances, digestibility of dry matter, nitrogen and energy, white and red blood cell counts, packed cell volume, and incidence of diarrhea. The PKE increased average daily gain (ADG) (246 vs 215 g/d; p = 0.06) and average daily feed intake (ADFI) (470 vs 343 g/d; p<0.05) and decreased gain-to-feed ratio (G:F) (0.522 vs 0.628 g/g; p<0.05) during phase 2 compared with CON, but did not affect growth performance during phase 1 and 3. During overall experimental period, PKE increased ADG (383 vs 362 g/d; p = 0.05) and ADFI (549 vs 496 g/d; p<0.05) compared with CON, but did not affect G:F. However, no differences were found on digestibility of dry matter, nitrogen, and energy between CON and PKE. The PKE reduced frequency of diarrhea (15% vs 25%; p = 0.08) for the first 2 wk after weaning compared with CON. Similarly, PKE decreased white blood cells (8.19 vs 9.56×10(3)/µL; p = 0.07), red blood cells (2.92 vs 3.25×10(6)/µL; p = 0.09), and packed cell volume (11.1% vs 12.6%; p = 0.06) on d 7 after weaning compared with CON. In conclusion, addition of 20% palm kernel expellers to nursery diet based on corn and soybean meal had no negative effects on growth performance, nutrient digestibility, and blood profiles of weaned pigs.
ABSTRACT
Data collected from 690 purebred Duroc pigs from 2009 to 2012 were used to estimate the heritability, and genetic and phenotypic correlations between production and meat quality traits. Variance components were obtained through the restricted maximum likelihood procedure using Wombat and SAS version 9.0. Animals were raised under the same management in five different breeding farms. The average daily gain, loin muscle area (LMA), backfat thickness (BF), and lean percent (LP) were measured as production traits. Meat quality traits included pH, cooking loss, lightness (L*), redness (a*), yellowness (b*), marbling score (MS), moisture content (MC), water holding capacity (WHC), and shear force. The results showed that the heritability estimates for meat quality traits varied largely from 0.19 to 0.79. Production traits were moderate to highly heritable from 0.41 to 0.73. Genotypically, the BF was positively correlated (p<0.05) with MC (0.786), WHC (0.904), and pH (0.328) but negatively correlated with shear force (-0.533). The results of genetic correlations indicated that selection for less BF could decrease pH, moisture content, and WHC and increase the shear force of meat. Additionally, a significant positive correlation was recorded between average daily gain and WHC, which indicates pork from faster-growing animals has higher WHC. Furthermore, selection for larger LMA and LP could increase MS and lightness color of meat. The meat quality and production traits could be improved simultaneously if desired. Hence, to avoid further deterioration of pork characteristics, appropriate selection of traits should be considered.
ABSTRACT
This experiment was conducted to investigate the effects of palm kernel expellers on productive performance, nutrient digestibility, and changes in white blood cells (WBC) of lactating sows. A total of 14 sows (200±12 kg of average body weight [BW]; 2.5 of average parity) were used and moved from gestation room to farrowing room on d 109 of gestation. Sows were randomly assigned to 2 dietary treatments in a completely randomized design. The treatments were a diet based on corn and soybean meal (CON) and CON added with 20% of palm kernel expellers (PKE). Sows were fed the treatments for 28 days (weaning) after farrowing. Blood was collected from each sow and 4 randomly selected piglets from each sow before farrowing or on d 3, 7, or 14 of lactation. Sows were fed respective treatments containing 0.2% chromic oxide from d 15 to 21 of lactation. Fecal samples were collected daily for the last 3 days after the 4-d adjustment period. Measurements were performances and WBC changes of sows and litter, nutrient digestibility of sows, and daily diarrhea of litter. Sows fed PKE had greater average daily feed intake (7.38 vs 7.10 kg/d; p<0.05) and lost less BW (-6.85 vs -8.54 kg; p<0.05) and backfat depth (-0.42 vs -0.71 mm; p<0.05) than those fed CON. However, there were no differences on digestibility of dry matter, nitrogen, and energy and weaning to estrus interval of sows fed either CON or PKE. Piglets from sows fed PKE gained more BW (203 vs 181 g/d; p = 0.08) and had less frequency of diarrhea (6.80 vs 8.56%; p = 0.07) than those from sows fed CON. On the other hand, no difference was found on preweaning mortality of piglets from sows fed either CON or PKE. Sows fed PKE had lower number of WBC (9.57 vs 11.82 ×10(3)/µL; p = 0.09) before farrowing than those fed CON, but no difference on d 3 and 7. Similarly, piglets from sows fed PKE had also lower number of WBC (7.86 vs 9.80 ×10(3)/µL; p<0.05) on d 14 of lactation than those from sows fed CON, but no difference on d 3 and 7. In conclusion, addition of 20% palm kernel expellers to lactation diet based on corn and soybean meal had no negative effects on productive performance, nutrient digestibility, and WBC changes of lactating sows.
ABSTRACT
Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that has a central role in the regulation of tumour metabolism under hypoxic conditions. HIF-1α stimulates glycolytic energy production and promotes tumour growth. Sirtuins are NAD(+)-dependent protein deacetylases that regulate cellular metabolism in response to stress; however, their involvement in the hypoxic response remains unclear. In this study, it is shown that SIRT2-mediated deacetylation of HIF-1α regulates its stability in tumour cells. SIRT2 overexpression destabilized HIF-1α under hypoxic conditions, whereas HIF-1α protein levels were high in SIRT2-deficient cells. SIRT2 directly interacted with HIF-1α and deacetylated Lys709 of HIF-1α. Deacetylation of HIF-1α by SIRT2 resulted in increased binding affinity for prolyl hydroxylase 2, a key regulator of HIF-1α stability, and increased HIF-1α hydroxylation and ubiquitination. Moreover, a pharmacological agent that increased the intracellular NAD(+)/NADH ratio led to the degradation of HIF-1α by increasing SIRT2-mediated deacetylation and subsequent hydroxylation. These findings suggest that SIRT2-mediated HIF-1α deacetylation is critical for the destablization of HIF-1α and the hypoxic response of tumour cells.
Subject(s)
Cell Hypoxia/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Sirtuin 2/metabolism , Animals , Cell Line, Tumor , Energy Metabolism/genetics , Female , HeLa Cells , Humans , Hydroxylation , Mice , Mice, Inbred BALB C , Mice, Nude , NAD/metabolism , Prolyl Hydroxylases/metabolism , Protein Binding , Protein Stability , RNA Interference , RNA, Small Interfering , Sirtuin 2/genetics , UbiquitinationABSTRACT
The oncogenic human papillomavirus (HPV) E6/E7 proteins are essential for the onset and maintenance of HPV-associated malignancies. Here, we report that activation of the cellular ubiquitin-proteasome system (UPS) by the omega-3 fatty acid, docosahexaenoic acid (DHA), leads to proteasome-mediated degradation of E6/E7 viral proteins and the induction of apoptosis in HPV-infected cancer cells. The increases in UPS activity and degradation of E6/E7 oncoproteins were associated with DHA-induced overproduction of mitochondrial reactive oxygen species (ROS). Exogenous oxidative stress and pharmacological induction of mitochondrial ROS showed effects similar to those of DHA, and inhibition of ROS production abolished UPS activation, E6/E7 viral protein destabilization, and apoptosis. These findings identify a novel role for DHA in the regulation of UPS and viral proteins, and provide evidence for the use of DHA as a mechanistically unique anticancer agent for the chemoprevention and treatment of HPV-associated tumors.
Subject(s)
Antiviral Agents/pharmacology , DNA-Binding Proteins/metabolism , Docosahexaenoic Acids/pharmacology , Oncogene Proteins, Viral/metabolism , Papillomavirus E7 Proteins/metabolism , Repressor Proteins/metabolism , Enzyme Activation/drug effects , Gene Expression Regulation , HeLa Cells , Host-Pathogen Interactions , Human papillomavirus 16/drug effects , Human papillomavirus 16/physiology , Human papillomavirus 18/drug effects , Human papillomavirus 18/physiology , Humans , Proteasome Endopeptidase Complex/drug effects , Proteasome Endopeptidase Complex/metabolism , Proteolysis/drug effects , Reactive Oxygen Species/agonists , Reactive Oxygen Species/metabolism , Signal Transduction , Ubiquitin/genetics , Ubiquitin/metabolism , Ubiquitination/drug effectsABSTRACT
New approaches for assessment of lymphedema using ultrasonography (US) have been introduced recently and are reported to be reliable and simple. Ultrasonography provides detailed information about physical properties of the tissue in addition to volume and size. There have been only limited studies comparing bioimpedance analysis (BIA), US, and circumferential measurement (CM), which is considered a standard measurement. The aim of this study was to determine the relationship between US, BIA, and CM. Twenty-eight patients with lymphedema after breast cancer surgery underwent BIA, US, and CM. Impedance, which reflects the amount of extracellular fluid, was measured with 1 kHz frequency in affected and unaffected arms. Circumferences were measured at 10cm proximal and distal to the elbow and a truncated cone method used to calculate estimated volumes for upper arm and forearm. We found that interlimb forearm subcutis thickness differences measured by US were highly correlated with CM measurements and that interlimb upper arm subcutis thickness differences measured by US were moderately correlated with CM measurements and BIA ratios. However, the interlimb ratio of compressibility measured by US showed no or only weak correlation with impedance measurements and circumferential measurements. Our results also show that compressibility measured by US could not be predicted from BIA or CM measurements despite a high degree of concordance among subcutis thickness measured by US, CM, and BIA.
Subject(s)
Anthropometry/methods , Breast Neoplasms/surgery , Lymphedema/diagnosis , Mastectomy/adverse effects , Upper Extremity/diagnostic imaging , Upper Extremity/pathology , Body Composition , Electric Impedance , Female , Humans , Lymphedema/diagnostic imaging , Lymphedema/etiology , Lymphedema/pathology , Middle Aged , Predictive Value of Tests , Severity of Illness Index , UltrasonographyABSTRACT
The objective of this study was to assess the role of teat skin colonization in Staphylococcus aureus intramammary infections (IMI) by evaluating genetic relatedness of Staph. aureus isolates from milk and teat skin of dairy cows using pulsed-field gel electrophoresis and characterizing the isolates based on the carriage of virulence genes. Cows in 4 known Staph. aureus-positive herds were sampled and Staph. aureus was detected in 43 quarters of 20 cows, with 10 quarters positive in both milk and skin (20 isolates), 18 positive only in milk, and 15 only on teat skin. Quarters with teat skin colonized with Staph. aureus were 4.5 times more likely to be diagnosed with Staph. aureus IMI than quarters not colonized on teat skin. Three main clusters were identified by pulsed-field gel electrophoresis using a cutoff of 80% similarity. All 3 clusters included both milk and skin isolates. The majority of isolates (72%) belonged to one predominant cluster (B), with 60% of isolates in the cluster originating from milk and 40% from teat skin. Genotypic variability was observed within 10 pairs (formed by isolates originating from milk and teat skin of the same quarter), where isolates in 5 out of the 10 pairs belonged to the same cluster. Forty-two virulence factors were screened using PCR. Some virulence factors were carried more frequently by teat skin isolates than by milk isolates or isolates from quarters with high somatic cell counts. Isolates in the predominant cluster B carried virulence factors clfA and clfB significantly more often than isolates in the minor clusters, which may have assisted them in becoming predominant in the herds. The present findings suggest that teat skin colonization with Staph. aureus can be an important factor involved in Staph. aureus IMI.
Subject(s)
Cattle Diseases/microbiology , Mammary Glands, Animal/microbiology , Milk/microbiology , Staphylococcal Infections/veterinary , Staphylococcus aureus/genetics , Virulence Factors/analysis , Animals , Cattle , Cattle Diseases/epidemiology , Cluster Analysis , Electrophoresis, Gel, Pulsed-Field/veterinary , Female , Genotype , Ohio/epidemiology , Prevalence , Skin/microbiology , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Staphylococcus aureus/classification , Staphylococcus aureus/isolation & purification , Staphylococcus aureus/pathogenicity , Virulence Factors/geneticsABSTRACT
Cisplatin (cis-diaminedichloroplatinum-II) is an extensively used chemotherapeutic agent, and one of its most adverse effects is ototoxicity. A number of studies have demonstrated that these effects are related to oxidative stress and DNA damage. However, the precise mechanism underlying cisplatin-associated ototoxicity is still unclear. The cofactor nicotinamide adenine dinucleotide (NAD(+)) has emerged as a key regulator of cellular energy metabolism and homeostasis. Here, we demonstrate for the first time that, in cisplatin-mediated ototoxicity, the levels and activities of SIRT1 are suppressed by the reduction of intracellular NAD(+) levels. We provide evidence that the decrease in SIRT1 activity and expression facilitated by increasing poly(ADP-ribose) transferase (PARP)-1 activation and microRNA-34a through p53 activation aggravates cisplatin-mediated ototoxicity. Moreover, we show that the induction of cellular NAD(+) levels using ß-lapachone (ß-Lap), whose intracellular target is NQO1, prevents the toxic effects of cisplatin through the regulation of PARP-1 and SIRT1 activity. These results suggest that direct modulation of cellular NAD(+) levels by pharmacological agents could be a promising therapeutic approach for protection from cisplatin-induced ototoxicity.
Subject(s)
Antineoplastic Agents/adverse effects , Cisplatin/adverse effects , Hearing Loss/chemically induced , NAD(P)H Dehydrogenase (Quinone)/metabolism , NAD/metabolism , Animals , Antineoplastic Agents/pharmacology , Cisplatin/pharmacology , Hearing Loss/genetics , Hearing Loss/metabolism , Hearing Loss/pathology , Male , Mice , Mice, Knockout , MicroRNAs/genetics , MicroRNAs/metabolism , NAD/genetics , NAD(P)H Dehydrogenase (Quinone)/genetics , Poly (ADP-Ribose) Polymerase-1 , Poly(ADP-ribose) Polymerases/genetics , Poly(ADP-ribose) Polymerases/metabolism , Sirtuin 1/genetics , Sirtuin 1/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolismABSTRACT
Adenylyl cyclase 2 (ADCY2), a class B member of adenylyl cyclases, is important in accelerating phosphor-acidification as well as glycogen synthesis and breakdown. Given its distinct role in flesh tenderization after butchering, we cloned and sequenced the ADCY2 gene from Yanbian cattle and assessed its expression in bovine tissues. A 2947 bp nucleotide sequence representing the full-length cDNA of bovine ADCY2 gene was obtained by 5' and 3' remote analysis computations for gene expression. Analyses of the putative protein sequence showed that ADCY2 had high homology among species, except with the non-mammal Oreochromis niloticus. Gene structural domain analyses in humans and rats indicated that the ADCY2 protein had no flaw; only the transmembrane domain was reduced and the CYCc structure domain was shortened. Assessment of ADCY2 expression in bovine tissues by real-time PCR showed that the highest expression was in the testes, followed by the longissimus dorsi, tensor fasciae latae, and latissimus dorsi. These data will serve as a foundation for further insight into the cattle ADCY2 gene.
Subject(s)
Adenylyl Cyclases/biosynthesis , Adenylyl Cyclases/genetics , Cloning, Molecular , Adenylyl Cyclases/chemistry , Amino Acid Sequence , Animals , Cattle , DNA, Complementary/genetics , Gene Expression , Glycogen/biosynthesis , Humans , Rats , Sequence Alignment , Sequence Homology, Amino AcidABSTRACT
BACKGROUND: Curcumin, the active ingredient of turmeric (Curcuma longa), has a wide range of beneficial effects including anti-inflammation and analgesia. However, poor bioavailability of curcumin hinders its clinical application. To overcome this limitation, we modified the structure of curcumin and synthesized new derivatives with favourable pharmacokinetic profiles. Recently, curcumin has been shown to have an antagonizing effect on transient receptor potential vanilloid type 1 (TRPV1) ion channels. We investigated the antinociceptive activity of KMS4034 which had the most favourable pharmacokinetics among the tested curcumin derivatives. METHODS: To evaluate the mechanism of the antinociceptive effects of KMS4034, capsaicin (I(CAP))- and heat (I(heat))-induced currents in TRPV1 expressing HEK293 cells were observed after the application of KMS4034. Nociceptive behavioural measurement using the hot-plate test, formalin test, and chronic constriction injury (CCI) model were evaluated in mice. Also, calcitonin gene-related peptide (CGRP) was stained immunohistochemically in the L4/5 dorsal horns in mice with neuropathic pain. RESULTS: I(CAP) (P<0.01) and I(heat) (P<0.05) of TRPV1 were significantly blocked by 10 µM KMS4034. Behaviourally, noticeable antinociceptive effects after 10 mg kg(-1) of KMS4034 treatment were observed in the first (P<0.05) and second phases (P<0.05) of the formalin and hot-plate tests. The mechanical threshold of CCI mice treated with 10 mg kg(-1) KMS4034 was significantly increased compared with control. Immunohistochemical CGRP expression was decreased in the lamina I-II of the lumbar dorsal horns in KMS4034-treated CCI mice compared with the control (P<0.05). CONCLUSIONS: KMS4034 may be an effective analgesic for various pain conditions.
Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Curcumin/analogs & derivatives , Inflammation/drug therapy , Neuralgia/drug therapy , TRPV Cation Channels/antagonists & inhibitors , Analgesics, Non-Narcotic/blood , Analgesics, Non-Narcotic/pharmacology , Animals , Calcitonin Gene-Related Peptide/metabolism , Cells, Cultured , Curcumin/pharmacology , Curcumin/therapeutic use , Drug Evaluation, Preclinical/methods , Formaldehyde , Hot Temperature , Inflammation/blood , Inflammation/chemically induced , Inflammation/metabolism , Male , Mice , Mice, Inbred ICR , Neuralgia/blood , Neuralgia/metabolism , Patch-Clamp Techniques , Physical Stimulation/methods , Posterior Horn Cells/metabolism , Reaction Time/drug effects , TRPV Cation Channels/physiologyABSTRACT
Staphylococci are a worldwide cause of human and animal infections including life-threatening cases of bacteraemia, wound infections, pyogenic lesions, and mastitis. Enterotoxins produced by some staphylococcal species were recognized as causative agents of staphylococcal food poisoning (SFP), being also able to interrupt human and animal immune responses. Only enterotoxins produced by Staphylococcus aureus were as yet well characterized. Much less is known about enterotoxigenic potential of coagulase-negative species of genus Staphylococcus (CNS). The pathogenic role of CNS and their enterotoxigenicity in developing SFP has not been well established. Although it has been reported that enterotoxigenic CNS strains have been associated with human and animal infections and food poisoning, most of research lacked a deeper insight into structure of elements encoding CNS enterotoxins. Recent studies provided us with strong evidence for the presence and localization of enterotoxin-coding elements in CNS genomes and production of enterotoxins. Thus, the importance of pathogenic potential of CNS as a source of staphylococcal enterotoxins has been highlighted in human and animal infections as well as in food poisoning.
Subject(s)
Enterotoxins/metabolism , Staphylococcal Food Poisoning/microbiology , Staphylococcal Infections/microbiology , Staphylococcus/physiology , Animals , Coagulase/genetics , Enterotoxins/analysis , Enterotoxins/chemistry , Humans , Staphylococcus/chemistry , Staphylococcus/enzymology , Staphylococcus/metabolismABSTRACT
Bovine calpastatin (CAST) gene polymorphisms have been associated with meat tenderness traits; however, little is known about how the CAST gene affects beef quality traits. In this study, 25 single nucleotide polymorphisms were detected in the CAST gene using polymerase chain reaction with single-strand conformation polymorphism and gene sequencing. Different preponderant genotypes were found at the corresponding gene locus. The E1-1, E1-2, and C3-1 loci were correlated with meat tenderness height and highly correlated with the fatty acid content and the amino acid content. The E4-2 locus was not correlated with meat tenderness, but it was correlated with cooking loss, brightness, and yellowness, among others. The CAST gene is a potential marker for these meat quality traits, but further research is required.
Subject(s)
Calcium-Binding Proteins/genetics , Meat/standards , Polymorphism, Single Nucleotide , Amino Acids/metabolism , Animals , Cattle/genetics , China , Fatty Acids/metabolism , Food Quality , Genetic Association Studies , Genotype , Male , Muscle, Skeletal/metabolism , Sequence Analysis, DNAABSTRACT
This study was performed to determine the influence of pig breed and gender on the ultimate pH and physicochemical properties of pork. The correlations between pH and pork quality traits directly related to carcass grade, and consumer's preference were also evaluated. The pH and meat grading scores for cold carcasses of 215 purebred pigs (Duroc, Landrace, and Yorkshire) from four different farms were obtained. Meat quality parameters of the pork loin were analyzed. Duroc and female animals were more affected compared to other breeds and male pigs. Duroc animals had the highest ultimate pH, carcass back fat thickness, marbling scores, yellowness, and fat content (p<0.05). Landrace pigs had the highest color lightness and cooking loss values (p<0.05). Among all trait parameters, marbling scores showed the highest significant differences when evaluating the impact of breed and gender on meat quality characteristics (p<0.001). Ultimate pH was positively correlated with carcass weight (0.20), back fat thickness (0.19), marbling score (0.17), and color score (0.16) while negatively correlated with cooking loss (-0.24) and shear force (-0.20). Therefore, pork samples with lower ultimate pH had lower cooking loss, higher lightness, and higher shear force values irrespective of breed.