SNP Group Research Articles

Local Regulation of Mitochondrial Respiratory for Enhancing Photodynamic Therapy and Breaking Chemoresistance in Hypoxia.

The hypoxic condition in solid tumors induces therapy resistance, limited therapeutic efficacy, and tumor recurrence, especially for chemotherapy and aerobic photodynamic therapy (PDT). To address this matter, an O2 regulator (SNP@Ato) is designed for breaking chemoresistance and enhancing PDT, which is constructed by loading Atovaquone (Ato) through self-assembly and host-guest interaction between β-cyclodextrin functionalized tetraphenylporphyrin (TPP-CD4) and thioketal-linked camptothecin/azobenzene (Azo-TK-CPT). Specifically, the porphyrin units in SNP@Ato are in "Off state" due to the photoinduced electron transfer (PET) effect between the porphyrin units and azobenzene. After encountering the hypoxic condition in solid tumors, SNP@Ato is dissociated by the cleaved azobenzene on account of over-expressed azo-reductase. Then the mitochondrial respiratory of cancer cells would be suppressed with the participation of Ato, generating a local hypoxia relief for sensitized chemotherapy and enhanced PDT. Accompanied by efficient PDT, the TK linker is broken by ROS, and the CPT is released from the prodrugs. Compared with the SNP group without oxygen-regulator, SNP@Ato exhibits a remarkable improvement of the therapeutic effect against hypoxic tumors in vitro and in vivo. This work proposes a novel paradigm for overcoming hypoxia-induced therapeutic resistance.

Empathy and self-regulation in prosocial accountability: Gender and genetic (OXTR SNP rs53576) pathways

ABSTRACT Empathy and self-regulation play key roles in prosocial accountability. Meta-analytic evidence for empathy—in relation to gender and a particular genetic variable (OXTR SNP rs53576) – guided design and power analysis to determine the size of this United States sample. We assessed 311 participants (51.4% female; 19% racial or ethnic minority). We conducted tests of hypothesized indirect effects of gender and genotype through empathy to trait and state accountability – reporting replication and extension tests of gratitude, forgivingness and relational repair in a supplement (https://doi.org/10.17605/OSF.IO/KZDF8). Gender tests controlled for SNP group and vice versa. Gender had indirect effects on accountability via empathy (higher in women than men). SNP group indirect effects on accountability via empathy (higher in GGs than A-carriers) showed roles of gender, race/ethnicity and self-regulation. SNP group also had indirect effects on accountability through self-regulation (higher in A-carriers than GGs). Findings underscore empathy and self-regulation in relational accountability and positive psychology.

Spanish Outbreak Isolates Bridge Phylogenies of European and American Bacillus anthracis.

The geographical origin of a major present-day phylogenetic group (A branch WNA; A.Br.WNA) of American Bacillus anthracis is controversial. One hypothesis postulated that the anthrax pathogen reached North America via a then-existing land bridge from northeastern Asia thousands of years ago. A competing hypothesis suggested that B. anthracis was introduced to America a couple of hundred years ago, related to European colonization. The latter view is strongly supported by genomic analysis of a group of French B. anthracis isolates that are phylogenetically closely related to the North American strains of the A branch A.Br.WNA clade. In addition, three West African strains also belong to this relationship group. Recently, we have added a Spanish strain to these close relatives of the WNA lineage of American B. anthracis. Nevertheless, the diversity of Spanish B. anthracis remains largely unexplored, and phylogenetic links to European or American relatives are not well resolved. Here, we genome sequenced and characterized 29 new B. anthracis isolates (yielding 18 unique genotypes) from outbreaks in west central and central Spain in 2021. Applying comparative chromosomal analysis, we placed the chromosomes of these isolates within the established phylogeny of the A.Br.008/009 (A.Br.TEA) canonical SNP group. From this analysis, a new sub-clade, named A.Br.11/ESPc, emerged that constitutes a sister group of American A.Br.WNA.

Determining the cardiovascular effects of nitric oxide in the dorsolateral Periaqueductal Gray (dlPAG) in anaesthetised rats

ObjectiveThe dorsolateral periaqueductal gray (dlPAG) is an area located in the brain stem that performs a host of functions including cardiovascular regulation. Owing to the presence of nitric oxide (NO) in this area, we investigated its effect on the cardiovascular system. MethodsWe divided rats into four groups: 1) control; 2) l-arginine (L-Arg, a precursor for nitric oxide, 60 nmol); 3) l-NAME (N omega-nitro-l-arginine methyl ester, a nitric oxide synthase inhibitor, 90 nmol); and 4) sodium nitroprusside (SNP, a nitric oxide donor, 27 nmol). After anaesthesia, the rats were mounted on a stereotaxic apparatus and the drugs were microinjected into the dlPAG. Cardiovascular parameters were continuously recorded by a PowerLab system connected to the cannulated femoral artery via a pressure transducer. The changes (Δ) of systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) were calculated at different times as compared to the control group. ResultsIn the l-NAME group, the ΔSBP, ΔMAP, and ΔHR were not significantly affected compared to the control group. In the L-Arg group, ΔSBP and ΔMAP increased; however, only SBP showed a significant increase compared to the control group. In the SNP group, SBP and MAP were significantly affected in comparison to the controls. Additionally, ΔHR decreased in both L-Arg and SNP, but was only significant in L-Arg. ConclusionOur study showed that NO of dlPAG has a pressor effect and attenuates baroreflex bradycardia. However, its pressor effect is more significant.

PROGNOSTIC IMPACT OF ISOCITRATE DEHYDROGENASE ENZYME ISOFORMS IDH1 & IDH2 MUTATIONS IN ACUTE MYELOID LEUKEMIA

Background: IDH1 & 2 mutations are one of the most common genomic abnormalities which have recently been described in acute myeloid leukemia (AML) patients. Mutant IDH1/2 enzymes have neomorphic activity and catalyze the reduction of ketoglutarate to an oncometabolite, which promotes DNA and histone hypermethylation, altered gene expression, and impaired hematopoietic differentiation. Aim of the work: To evaluate the prognostic impact of both IDH1 and IDH2 mutations in newly diagnosed AML patients and their correlation with different clinical and laboratory parameters.Patients and Methods: The present study was conducted on 56 de novo adult AML patients who attended Haematology/Oncology unit of Ain-Shams University Hospitals during the period from July 2017 till July 2018. They were assessed for the presence of IDH 1& 2 SNP mutations using Real-Time PCR Patients with MDS, biphenotypic leukemia and associated malignancy were excluded from our study. Results: Heterozygous mutations of IDH1 SNP rs11554137& IDH2R140Q SNP were detected in a percentage of 14.3% and 16.1% respectively. Upon assessing the clinical outcome at day 28, mutant IDH2R140Q SNP group showed significant unfavourable outcome(p=0.045). While at 6 months, all patients with IDH1 SNP rs11554137mutation died and seven out of nine patients with mutant IDH2R140Q died,so IDH1 SNP rs11554137 showed significant unfavourable outcome at 6 months(p=0.016).The survivors showedsignificantly younger age, lower mean platelets and blast counts, as well as negative IDH1 SNP rs11554137 (p= 0.014, 0.046, 0.009 and 0.016 respectively)Multivariate logistic regression analysis identified high BM blasts percentage as an independent prognostic predictor for 6 month mortality ( p=0.014, OR 1.049, 95% CI 1.010 to 1.090). Conclusion: IDH1 SNP rs11554137 in CN-AML is associated with unfavourable clinical outcome and worse DFS at 6months,and was univariate factor in non survivors patients.while IDH2R140Q was associated with unfavourable clinical outcome at day28 after induction.Including IDH1&IDH2 mutations in AML routine gene panel,will be valuable for prognostication.

Potential role of sympathetic activity on the pathogenesis of massive pulmonary embolism with circulatory shock in rabbits

BackgroundWe recently showed that intravenous sodium nitroprusside treatment (SNP) could relieve the pulmonary vasospasm of pulmonary embolism (PE) and non-pulmonary embolism (non-PE) regions in a rabbit massive pulmonary embolism (MPE) model associated with shock. The present study explored the potential role of cardiopulmonary sympathetic activity on the pathogenesis and the impact of vasodilators on cardiopulmonary sympathetic activity in this model.MethodsRabbits were randomly divided into sham operation group (S group, n = 8), model group (M, equal volume of saline intravenously, n = 11), SNP group (3.5 μg/kg/min intravenously, n = 10) and diltiazem group (DLZ, 6.0 μg/kg/min intravenously, n = 10).ResultsMPE resulted in reduced mean arterial pressure and increased mean pulmonary arterial pressure as well as reduced PaO2 in the M, SNP and DLZ groups. Tyrosine hydroxylase (TH), neuropeptide Y (NPY) and endothelin-1 (ET-1) expression levels were significantly increased, while nitric oxide (NO) levels were reduced in both PE and non-PE regions in the M group. Both SNP and DLZ decreased mean pulmonary arterial pressure, reversed shock status, downregulated the expression of TH, NPY and ET-1, and increased NO levels in PE and non-PE regions.ConclusionPresent results indicate that upregulation of the sympathetic medium transmitters TH and NPY in whole lung tissues serves one of the pathological features of MPE. The vasodilators SNP and DLZ could relieve pulmonary vasospasm in both embolization and non-embolization regions and reverse circulatory shock, thereby indirectly downregulating the sympathetic activation of the whole lung tissues and breaking a vicious cycle related to sympathetic activation in this model.

Strategies of Increased Protein Intake in ELBW Infants Fed by Human Milk Lead to Long Term Benefits.

Objective: The aim of this observational study was to evaluate the effects of two different protein intake regimes on feeding tolerance, in-hospital growth, anthropometric data and psychomotor outcome up to 24 months corrected age (CA) in extremely low birth-weight (ELBW; birth weight <1000 g) infants.Methods: During the period 2008–2013, 52 ELBW infants admitted at birth to two Neonatal Intensive Care Units of Emilia Romagna (Italy) were fed according to different protocols of protein fortification of human milk: an estimated protein intakes at maximum fortification levels of 3.5 gr/kg/day in the Standard Nutrition Population-SNP group (n = 26) and 4.8 g/kg/day in the Aggressive Nutrition Population-ANP group (n = 26). During hospitalization, infants' growth, biochemical indices of nutritional status, enteral intake, feeding tolerance, clinical history and morbidity were evaluated. After discharge, anthropometric data and psychomotor outcome, evaluated by Revised Griffiths Mental Development Scales (GMDS-R) 0–2 years, were assessed up to 24 months CA.Results: During hospitalization, the ANP group showed significantly higher weight (18.87 vs. 15.20 g/kg/day) and head circumference (0.70 vs. 0.52 cm/week) growth rates compared to SNP, less days of parenteral nutrition (7.36 ± 2.7 vs. 37.75 ± 29.6) and of hospitalization (60.0 ± 13.3 vs. 78.08 ± 21.32). After discharge, ANP infants had a greater head circumference compared to SNP (45.64 ± 0.29; 46.80 ± 0.31). Furthermore, the General Quotient of GMDS-R mean scores in the SNP group significantly decreased from 12 to 24 months CA, while no difference was seen in the ANP group.Conclusions: Increased protein intake may provide short and long term benefits in terms of growth and neurodevelopment in human milk-fed ELBW infants.

Acute Beneficial Effects of Sodium Nitroprusside in a Rabbit Model of Massive Pulmonary Embolism Associated with Circulatory Shock

We established a rabbit model of acute massive pulmonary embolism (PE) with associated circulatory shock using autologous blood clots. Rabbits were randomly assigned to a sham operation group (Sgroup), model group (M group; equal volume of saline intravenously after shock), and sodium nitroprusside group (SNP group; sodium nitroprusside intravenously after shock). SNP treatment significantly decreased mean pulmonary arterial pressure and increased mean arterial pressure and arterial partial pressure of oxygen and resulted in a partial reversal of the acute circulatory failure. The shock-reversal rate was 0% in the M group and 80% in the SNP group. Moreover, pulmonary artery angiography and echocardiography examinations evidenced alleviated PE-induced changes after SNP therapy. 5-Hydroxytryptamine was significantly reduced in both PE and non-PE tissues, thromboxane A2 level was significantly reduced in PE and tended to be lower in non-PE tissues, neutrophil accumulation was significantly reduced in both PE and non-PE tissues after SNP therapy. Our study demonstrated that pulmonary vasospasm in the nonembolic region might be a major pathologic factor leading to reduced left ventricular filling and circulatory shock after massive PE. Reduction of pulmonary vasospasm in the nonembolic area after SNP might serve as a major therapeutic mechanism involved in the observed beneficial effects of SNP in this model.

The First Norovirus Longitudinal Seroepidemiological Study From Sub-Saharan Africa Reveals High Seroprevalence of Diverse Genotypes Associated With Host Susceptibility Factors.

BackgroundHuman noroviruses (HuNoVs) are a prominent cause of gastroenteritis, yet fundamental questions remain regarding epidemiology, diversity, and immunity in sub-Saharan African children. We investigated HuNoV seroprevalence and genetic and sociodemographic risk factors in Ugandan children.MethodsWe randomly screened 797 participants of a longitudinal birth cohort (Entebbe, EMaBS) and 378 from a cross-sectional survey (rural Lake Victoria, LaVIISWA), for antibodies against HuNoV genotypes by ELISA. We used linear regression modeling to test for associations between HuNoV antibody levels and sociodemographic factors, and with the human susceptibility rs601338 FUT2 secretor SNP and histo-blood group antigens (A/B/O).ResultsOf EMaBS participants, 76.6% were seropositive by age 1, rising to 94.5% by age 2 years. Seroprevalence in 1 year olds of the rural LaVIISWA survey was even higher (95%). In the birth cohort, 99% of seropositive 2 year olds had responses to multiple HuNoV genotypes. We identified associations between secretor status and genogroup GII antibody levels (GII.4 P = 3.1 × 10−52), as well as ABO and GI (GI.2 P = 2.1 × 10−12).ConclusionsHuNoVs are highly prevalent in Ugandan children, indicating a substantial burden of diarrhea-associated morbidity with recurrent infections. Public health interventions, including vaccination, and increased surveillance are urgently needed.

Weighted Genetic Risk Scores and Prediction of Weight Gain in Solid Organ Transplant Populations.

BackgroundPolygenic obesity in Solid Organ Transplant (SOT) populations is considered a risk factor for the development of metabolic abnormalities and graft survival. Few studies to date have studied the genetics of weight gain in SOT recipients. We aimed to determine whether weighted genetic risk scores (w-GRS) integrating genetic polymorphisms from GWAS studies (SNP group#1 and SNP group#2) and from Candidate Gene studies (SNP group#3) influence BMI in SOT populations and if they predict ≥10% weight gain (WG) one year after transplantation. To do so, two samples (nA = 995, nB = 156) were obtained from naturalistic studies and three w-GRS were constructed and tested for association with BMI over time. Prediction of 10% WG at one year after transplantation was assessed with models containing genetic and clinical factors.Resultsw-GRS were associated with BMI in sample A and B combined (BMI increased by 0.14 and 0.11 units per additional risk allele in SNP group#1 and #2, respectively, p-values<0.008). w-GRS of SNP group#3 showed an effect of 0.01 kg/m2 per additional risk allele when combining sample A and B (p-value 0.04). Models with genetic factors performed better than models without in predicting 10% WG at one year after transplantation.ConclusionsThis is the first study in SOT evaluating extensively the association of w-GRS with BMI and the influence of clinical and genetic factors on 10% of WG one year after transplantation, showing the importance of integrating genetic factors in the final model. Genetics of obesity among SOT recipients remains an important issue and can contribute to treatment personalization and prediction of WG after transplantation.

‘Take us with you Scotland’? Post-Referendum and Post-Election Reflections from the North East Of England

This article examines the different reactions in North East England to the results of both the Scottish Independence Referendum in September 2014 and the General Election in May 2015. It outlines how the region's relief at the ‘No’ vote quickly gave way to traditional fears – once the Smith Commission had reported – that a more powerful Scotland would undermine economic fortunes just south of the border. To fear of a more powerful ‘neighbour’ was added a noticeable level of political hostility towards the SNP in particular, as the virtual wipe out of Labour MP's in Scotland in May's General Election has left many North East Labour politicians (in the party's one remaining heartland) uncertain and anxious about their own political future. However, the North East of England has also tried to harness the referendum outcome in more practical ways. In the first instance, using it to strengthen its own case to Westminster for greater devolved powers and, secondly, to explore opportunities for a more collaborative, cross-border approach to economic development. The article concludes by contrasting the growing disjunction between the increasingly sympathetic and supportive views of North Easterners towards what's happening in Scotland, and the hostile views of many North East Labour politicians. Those advocating that the region should work with the Scots, and gain the support of more powerful SNP group in Westminster for greater devolution in England, have a real challenge to overcome the hostile views of North East politicians towards both nationalism and nationalists.

Protective Effect of Nitric Oxide on Liver Circulation from Ischemia Reperfusion Injury

ABSTRACTIntroduction: The reduction of endogenous nitric oxide (NO) production during hepatic ischemia-reperfusion injury, generally via a reduction in endothelial NO synthase activity, leads to liver injury. We hypothesized that administration of an exogenous NO donor into the portal vein may ameliorate hepatic blood flow reduction after a period of ischemia.Material and Methods: A total of 90 min of ischemia (portal vein and hepatic artery) was applied in 15 anesthetized pigs, using the Pringle method under sevoflurane anesthesia. All animals were administered either saline (control group, n = 8) or sodium nitroprusside (SNP, n = 7) as exogenous NO donor drugs into the portal vein, 30 min before and after ischemia. The portal venous blood flow and hepatic artery blood flow were measured continuously using transonic flow probes attached to each vessel. Endogenous NO (NOx = NO2− + NO3−) production was measured every 10 min using a microdialysis probe placed in the left lobe of the liver.Results: In the SNP group, portal venous flow remained unchanged and hepatic artery flow significantly increased compared to baseline. Although the production of liver tissue NOx transiently decreased to 60% after ischemia, its level in the SNP group remained higher than the control saline group.Conclusion: Regional administration of SNP into the portal vein increases hepatic arterial flow during ischemia reperfusion periods without altering mean systemic arterial pressure. We speculate that administration of an exogenous NO donor may be effective in preventing liver injury via preservation of total hepatic blood flow.

229 SHORT-TERM EXPOSURE OF MATURE OOCYTES TO A NITRIC OXIDE DONOR FOR INDUCING OXIDATIVE STRESS RESISTANCE ON IN VITRO-PRODUCED BOVINE EMBRYOS

Recent studies have shown that short-term exposure of oocytes to stressors such as hydrostatic pressure, osmotic stress, and oxidative stress might induce stress tolerance in embryos. In this research we studied the effect of short-term exposure of bovine in vitro-matured cumulus-oocyte complexes (COC) with a nitric oxide donor (SNP) on IVF, embryo development, embryo quality, and relative gene expression related to cell redox state regulation. The COC were selected and matured in TCM 199 supplemented with 10% inactivated FBS, 6 mg mL–1 of LH, 6 mg mL–1 of FSH, 1 mg mL–1 of oestradiol, and 0.2 mmol of pyruvate and then incubated for 22 to 24 h at 38.5°C in 5% CO2 in a humidified atmosphere (n = 12). Before IVF, mature COC were incubated during 1 h with different concentration of sodium nitroprusside, SNP (control without SNP, 10–6 M, 10–5 M, and 10–4 M SNP) in maturation media at 38.5°C and 5% CO2 in a humidified atmosphere. For IVF procedure, oocytes of each treatment and sperm of one bull were co-incubated for 18 to 20 h at 38.5°C and 5% CO2. Presumptive zygotes were separately cultured until Day 7 under mineral oil at 38.5°C and 5% CO2, 5%O2, and 90% N2 in a humidified atmosphere. Embryo quality was analysed by staining with CDX2 antibody for trophectoderm cells and compared with total embryo cells stained with Hoechst 33342. Relative gene expression for each treatment were evaluated after RNA extraction and cDNA synthesis in Stratagene MX 3000P real-time equipment with Agilent qPCR software MX pro 4.1 version. Differences between experimental groups (n = 12) were measured using a one-way ANOVA test in the STATGRAPHICS plus 5.1 version software. P &lt; 0.05 was considered statistically significant. Cleavage percentage at 72 h post-insemination was significantly different between the control and 10–4 M SNP group (82 ± 8.4% v. 77 ± 7.1%, respectively) and between 10–5 M and 10–4 M SNP group (84.9 ± 4.1% v. 77 ± 7.1%, respectively). Blastocyst percentage at 7 days of culture was significantly different between control and 10–4 M SNP group (34.1 ± 7.8% v. 26.2 ± 4.9%, respectively). Embryo development between control group and treatments was similar within early, expanded, and hatched blastocyst percentage. Embryo quality of expanded blastocyst was similar between control group and treatments (ICM: TE). No significant differences in gene expression after SNP exposure was observed (iNOS, eNOS, nNOS, PRDX5, HSP70, HSP90, HIF1A, BCL2A). Oocytes incubated with a high concentration of SNP showed lower cleavage and blastocyst rates, showing that this treatment was deleterious for in vitro embryo production in bovine. However, there were no significant differences on embryo quality assessed by ICM : TE ratio and/or in gene expression pattern of 7-day cultured expanded blastocysts.

Erratum: HPA axis genetic variation, cortisol and psychosis in major depression

Correction to: Molecular Psychiatry (2014) 19, 220–227; doi:10.1038/mp.2013.129 In footnote a in Table 1 (‘Less than five total in the rare homozygous, collapsed into the heterozygous SNP group’), the number ‘five’ should have been ‘four’. In addition, there were errors in Supplementary Table S1, inthe rows for CRH-R2 and Nr3c2 (MR).

Obesity treatment: results after 4 years of a Nutritional and Psycho-Physical Rehabilitation Program in an outpatient setting

Obesity is a chronic disease as well as a risk factor for cardiovascular, metabolic and osteoarticular diseases, affecting the psychosocial health and the quality of life. Recent evidence suggests that the adequate treatment of obesity should provide a multidimensional multidisciplinary approach including nutritional therapy, psycho-educational classes and physical reconditioning/motor rehabilitation. The aim of this approach should be to maintain the results over time with a positive impact on the obesity-related cardiovascular and metabolic risk. To evaluate the effectiveness of a multidisciplinary Nutritional and Psycho-Physical Reconditioning Program (NPPRP) in an outpatient setting. The observational prospective cohort study involved subjects, aged from 18 to 65 years, with a BMI >30 kg/m(2), who were followed up over 48 months. After the first nutritional and psychological examination, patients who refused NPPRP were treated according to standard nutrition procedures (SNT). Patients were followed through monthly medical examinations and then by annual telephonic structured interviews for 4 years. Changes in body weight, eating behavior, physical activity performance, and the occurrence of clinical obesity-related complications were considered as outcome measures. Of 464 enrolled patients, 161 (34.7%) took part in the follow-up. From the enrollment to the end of follow-up, weight loss was greater in the NPPRP group than in the SNP group (-8.08 ± 10 kg versus -3.0 ± 6 kg). After 4 years eating behavior improved in both groups. The percentage of patients who continued to perform physical activity was higher in the NPPRP group than in the SNT group (61.0 versus 34.1%). The SNT group reported complications more frequently than the NPPRP group: hypertension (19 versus 5.8%), dyslipidemia (19.4 versus 12.7%), and skeletal problems (26.9 versus 17.5%). The main reasons for drop-out from the rehabilitation program were logistic problems (distance or time) in both groups; disappointment was higher in the SNT group than in the NPPRP group (37.8 versus 15.6%). A multidimensional multidisciplinary approach including nutritional intervention and psycho-physical rehabilitation, set against a conventional diet therapy, was more effective in the long-term outcome of obesity with regard to weight loss, physical activity, possible eating disorders, and obesity-related complications.

Genetic polymorphisms in Japanese fragrant landraces and novel fragrant allele domesticated in northern Japan.

Rice fragrance is an important characteristic for Southeast Asian consumers, and fragrant landraces from Japan were first recorded in the 17th century. Principal component analysis clearly showed that Japanese fragrant landraces were genetically different from non-Japanese fragrant landraces. Japanese fragrant landraces were composed of six clades, none of which carried the most common fragrance mutation, an 8-bp deletion in exon 7 of Badh2. Fragrant landraces comprised two major groups carrying different Badh2 mutations. One group carried a known SNP at exon13 and the other a SNP at the exon1-intron1 junction as splicing donor site. The latter was considered to be a potential splicing mutant group as a novel allele at Badh2. Heterozygosity (He) scores in the two fragrant groups were not significantly different from non-fragrant landraces and modern cultivars. However, lower He scores were found around the Badh2 locus in the two groups. The potential splicing mutant group showed a more extended haplotype than the E13 SNP group. A likely causal factor responsible for loss of function is a novel splicing mutation allele that may have been generated quite recently. The fragrance allele has dispersed as a result of out-crossing under local environmental conditions.

The effects of systemic chemical sympathectomy on local bone loss induced by sciatic neurectomy

BackgroundIt has been suggested that the sympathetic nervous system (SNS) is involved in bone metabolism and that blockade of the SNS could reduce bone loss and stimulate bone formation. However, the question of whether suppression of SNS tone could compensate for mechanical unloading-induced bone loss must be further clarified. The purpose of this study was to investigate whether systemically inhibiting sympathetic nervous system (SNS) tone could prevent bone loss from mechanical-inactivity-induced osteopenia. MethodsFemale Wistar rats (12 weeks old) were randomly assigned to three groups: the SN group (n = 10), or single leg sciatic neurectomy group; the SNP group (n = 12), or single leg sciatic neurectomy? propranolol treatment (0.5 g/L in dietary water) group; and the CON group (n = 10), or single leg sham-operated group. Animals were fed with distilled water or propranolol in water, in accordance with their group design, for 30 days. Histomorphometry, geometry, tissue weight, and serum markers were assessed. ResultsPropranolol-treated animals drank significantly less water, but did not differ in daily chow consumption or body weight gain. In histomorphometric analysis, the spongy bone volume ratio in proximal tibiae was significantly lower in the two sciatic neurectomy groups, but there was no difference between the SN and SNP groups. Architecture analysis showed that the SN group had significantly thinner trabeculae and fewer trabeculae than the CON group (p < 0.05), but there was no difference between the SNP and CON groups. There were no significant differences for tissue weight, geometric measurement, or serum markers assay. ConclusionIt was observed that blockade of the SNS prevented neurectomy-induced bone resorption, as demonstrated by various histomorphometric data, although the difference between SN and SNP did not reach significance. In further work it would be valuable to study possible gender, age, and dose-dependent efficacy of propranolol on bone metabolism.

Melatonin Attenuates Nitric Oxide Induced Oxidative Stress on Viability and Gene Expression in Bovine Oviduct Epithelial Cells, and Subsequently Increases Development of Bovine IVM/IVF Embryos

The objective of the present study was to elucidate the fundamental mechanism of bovine oviduct epithelial cell (BOEC) co-culture on developmental capacity of bovine IVM/IVF embryos and to determine whether or not melatonin acts as an antioxidant in BOEC culture and subsequent embryo development. These studies examined the effects of melatonin against NO-induced oxidative stress on cell viability, lipid peroxidation (LPO) and the expression of antioxidant genes (CuZnSOD, MnSOD and Catalase) or apoptosis genes (Bcl-2, Caspase-3 and Bax) during BOECs culture. We also evaluated the developmental rates of bovine IVM/IVF embryos with BOEC co-culture, which were pre-treated with melatonin () in the presence or absence of sodium nitroprusside (SNP, ) for 24 h. Cell viability in BOECs treated with SNP (50-) decreased while melatonin addition (1-) increased viability in a dose-dependent manner. Cell viability in melatonin plus SNP () gradually recovered according to increasing melatonin addition (1-). The LPO products were measured by thiobarbituric acid (TBA) reaction for malondialdehyde (MDA). Addition of melatonin in BOEC culture indicated a dose-dependent decrease of MDA, and in the SNP group among BOECs treated with SNP or melatonin plus SNP groups MDA was significantly increased compared with SNP plus melatonin groups (p melatonin group. These results suggest that melatonin has an anti-oxidative effect against NO-induced oxidative stress on cell viability of BOECs and on the developmental competence of bovine IVM/IVF embryo co-culture with BOEC.

Antioxidative Effects of Astaxanthin against Nitric Oxide‐Induced Oxidative Stress on Cell Viability and Gene Expression in Bovine Oviduct Epithelial Cell and the Developmental Competence of Bovine IVM/IVF Embryos

The aim of the present study was to elucidate the fundamental mechanism of bovine oviduct epithelial cell (BOEC) co-culture on developmental capacity of bovine in vitro oocyte maturation/in vitro fertilization (IVM/IVF) embryos. We examined the effects of astaxanthin against nitric oxide-induced oxidative stress on cell viability by MTT assay, lipid peroxidation (LPO) by using thiobarbituric acid (TBA) reaction for malondialdehyde (MDA) and the expression of antioxidant genes (CuZnSOD, MnSOD and Catalase) or apoptosis genes (Bcl-2, Caspase-3 and Bax) by RT-PCR in BOEC. We also evaluated the developmental rates of bovine IVM/IVF embryos co-cultured with BOEC pre-treated with astaxanthin (500 μM) in the presence or absence of sodium nitroprusside (SNP, 1000 μM) for 24 h. Cell viability in BOEC treated with SNP (50-2000 μM) lowered, while astaxanthin addition (50-500 μM) increased it in a dose-dependent manner. Cell viability in astaxanthin plus SNP (1000 μM) gradually recovered according to the increase in astaxanthin additions (100-500 mM). The LPO in astaxanthin group (50-500 μM) gradually decreased in a dose dependent manner and among SNP or astaxanthin plus SNP group, SNP alone and astaxanthin (50 μM) plus SNP shown a significant increase than other groups (p < 0.05). Expression of apoptosis or antioxidant genes was detected by RT-PCR. Bcl-2 and antioxidant genes were detected in astaxanthin or astaxanthin plus SNP group, and Caspase-3 and Bax genes were only found in SNP group. When bovine IVM/IVF embryos were cultured for 6-7 days under co-culture system such as BOEC treated with astaxanthin in the presence or absence of SNP, the developmental ability to blastocysts in 500 μM astaxanthin group was the highest of all groups. These results suggest that astaxanthin has a antioxidative effect on cell viability and LPO of BOEC, and development of bovine IVM/IVF embryos due to the induction of antioxidant genes and suppression of apoptosis genes.

Dexmedetomidine as a hypotensive agent: Efficacy and hemodynamic response during spinal surgery for idiopathic scoliosis in adolescents

BackgroundThis study was designed to evaluate the efficacy of dexmedetomidine as a hypotensive agent in comparison to sodium nitroprusside in scoliosis surgery.MethodForty patients ASA I or II aged (12–16) year scheduled for scoliosis surgery were randomly assigned to receive either dexmedetomidine 1 μg/kg over 10 min before induction of anesthesia followed by 0.2–0.5 μg/kg/h infusion during maintenance (DEX group) or sodium nitroprusside 1–10 μg/kg/min infusion after induction of anesthesia (SNP group) to maintain mean arterial blood pressure between (60–65 mmHg). Mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI) and stroke index (SI) were recorded. The two groups were compared with reference to reversibility of hypotensive state, intraoperative blood loss and transfusion requirement.ResultsDexmedetomidine administration resulted in significant reduction in MAP, HR and CI. During the steady state hypotension SNP group showed significant increase in HR and CI compared to baseline and to DEX group (P < 0.05). SVRI was significantly lower during controlled hypotension in SNP group compared to DEX group (P < 0.001). Time to restoration of baseline MAP was longer with DEX group (10.21 ± 1.52 min) than SNP group (4.87 ± 0.86 min) (P < 0.001). Blood loss and transfusion requirement were significantly lower in DEX group than SNP group [1095.62 ± 128.9 6 ml versus 1287.50 ± 182.54 ml, P = 0.0013] and [855.42 ± 140.23 versus 1006.00 ± 154.66 ml, P = 0.0026], respectively.ConclusionDexmedetomidine is a safe and effective drug for controlled hypotension in scoliosis surgery. It may offer the significant advantage of reducing blood loss and transfusion requirement.