Berberine inhibits experimental varicocele-induced cell cycle arrest via regulating cyclin D1, cdk4 and p21 proteins expression in rat testicles.

The aim of this study was to uncover the protective effect of berberine (BBR), an antioxidant chemical, on experimental varicocele (VCL)-induced adverse effects on cell cycle machinery during early germ cells mitosis. To follow-up this study, 30 mature male Wistar rats were divided into control-sham, nontreated VCL, 50 mg kg-1 and 100 mg kg-1 BBR-treated VCL groups. Following 60 days, histological alterations were analysed by haematoxylin and eosin (H and E) staining, and expressions of cyclin-D1, cyclin-dependent kinase-4 (cdk4) and p21 were investigated by immunohistochemical (IHC) staining technique. Finally, DNA ladder test was carried out to examine the testicular DNA fragmentation. Administration of BBR remarkably diminished the percentage of seminiferous tubules with deformed shape, depleted germ cells and germ cells dissociation compared to VCL-sole group. The IHC observations showed that BBR significantly (p < .05) reduced VCL-induced p21 expression increase and up-regulated cyclin-D1 and cdk4 expressions. Moreover, BBR decreased VCL-induced DNA fragmentation. In conclusion, BBR can promote cell cycle through cellular DNA content protection, p21 expression down-regulation and maintaining cyclin-D1 and cdk4 expressions. Thus, BBR could be considered as a novel protective biochemical agent against experimental VCL-induced derangements. However, more studies are needed to uncover BBR-induced effects on cells cycle process and germ cells development.

Association of serum gamma-glutamyltransferase and premature coronary artery disease.

BACKGROUND: Serum gamma-glutamyltransferase (GGT) has been introduced as a predictive factor for cardiovascular disease. In this study, we investigated the association of serum GGT and premature coronary artery disease (CAD) in candidates for coronary angiography. METHODS: In this cross-sectional study, we enrolled male subjects aged ≤45 years and female subjects ≤55 years who were candidates for elective coronary angiography due to typical chest pain or a positive non-invasive test. Baseline characteristics were recorded for all the participants and serum levels of blood glucose, lipid profile and GGT were measured. Patients were divided into CAD and non-CAD groups based on angiography for further comparisons. RESULTS: From a total of 367 patients (age 45.1 ± 6.1 years, 161 males [43.9%]), 176 (47.9%) patients had premature CAD. A high level of GGT was significantly associated with the presence of CAD (p < 0.001). A 10-unit increase in GGT could strongly predict the presence of premature coronary artery disease (OR: 13.34, 95% CI: 7.19-24.78; p < 0.001) after adjustment for confounders. The area under the receiver operating characteristic curve for GGT was 80.9% (range 76.5-85.3) and the sensitivity and specificity of GGT at a cut-point of 22.5 IU/l was 80.1% and 70.2%, respectively. Diagnostic accuracy of GGT was 74.9%. The positive predictive value and negative predictive value for GGT was 71.3 and 79.3, respectively. CONCLUSION: We observed that GGT levels in patients with typical chest pain or positive non-invasive tests could predict the presence of premature CAD in young patients.

Providing ramps during lay has larger impacts on laying hens than ramps at rearing.

Commercial laying hen housing is shifting from traditional cages to non-cage housing systems, such as the aviary, which has gained popularity due to potential for more species-typical behavior. However, birds housed in aviaries may have difficulties moving through the vertical tiers of the system leading to health problems such as keel bone fracture (KBF). One possible way to improve movement is to add ramps into an aviary system, allowing hens to walk between tiers rather than jump or fly. The objective of this study was to evaluate the impact of adding ramps to rearing and laying aviaries on bird health, production, and movement across vertical tiers of the aviary. Lohmann Selected Leghorn pullets were raised in 2 treatments: 4 pens (600 birds/pen) were raised with wire mesh ramps to aid movement between aviary tiers (RR) and 4 pens (600 birds/pen) were raised without ramps (RO). At 17 wk of age (WOA), birds were moved to the laying facility, in which 16 aviary pens with 225 birds/pen were populated. Half the pens (n = 8) were supplemented with wire mesh ramps (LR) and the other half were not (LO). Within each laying treatment group, 4 pens were populated with RR hens and 4 pens were populated with RO hens, creating 4 treatment combinations (RRLR, RRLO, ROLR, ROLO). From each pen, 15 focal hens were selected for radiographic imaging of their keel bones taken at 21, 36, 45, and 60 WOA and the images were subsequently scored for KBF severity. Focal hens were also scored for feather condition and footpad quality at 36 and 60 WOA using a standardized welfare assessment protocol. The number of downward transitions among aviary areas and falls were recorded at 19 to 20 and 30 to 31 WOA. Data were analyzed using (generalized) linear mixed models in R software. When ramps were available, they were used in most of the observed downward transitions (79% in ROLR and 86% in RRLR). Hens who received ramps in lay (i.e., RRLR and ROLR) showed more transitions immediately after lights on compared to midday or dusk phases (p < 0.001), performed more transitions from the first aviary tier compared to nest or top tier (p = 0.013) and had lower KBF severity than those who did not receive ramps in the laying aviaries (ROLO, RRLO; p < 0.001). At 60 WOA, hens in the RRLR treatment had greater feather coverage than those in ROLR and RRLO treatments (p < 0.001). Birds in the RRLR treatment had better foot health overall than those in treatments without ramps in lay (p = 0.018). Providing ramps to hens in aviaries appeared to be the preferred means of transitioning between aviary tiers though had positive effects on welfare parameters such as food health, feather coverage, and KBF severity, without negative impacts on production. Benefits were seen primarily when ramps were provided in lay, though their installation in rearing provided evidence of easier adaptation to the laying barn. Our study supports providing ramps throughout the lifetime of the bird to accommodate hens' preferred means of moving vertically in aviaries and deliver consequent benefits to health and welfare.

Early onset metastatic colorectal cancer in Australia.

BACKGROUND: Colorectal cancer (CRC) incidence and mortality rates have been increasing among young patients (YP), for uncertain reasons. It is unclear whether YP have a distinct tumor biology or merit a different treatment approach to older patients (OP). METHODS: We reviewed prospectively collected data from consecutive patients with metastatic CRC (MCRC) enrolled in the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Australian registry. Clinicopathological features, treatment and survival outcomes were compared between YP (<50 years) and OP (≥50 years). RESULTS: Of 3692 patients diagnosed August 2009 - March 2023, 14 % (513) were YP. YP were more likely than OP to be female (52% vs. 40 %, P < 0.0001), have ECOG performance status 0-1 (94% vs. 81 %, P < 0.0001), to have a left-sided primary (72% vs. 63 %, P = 0.0008) and to have fewer comorbidities (90% vs. 60 % Charleston score 0, P < 0.0001). There were no differences in the available molecular status, which was more complete in YP. YP were more likely to have de novo metastatic disease (71% vs. 57 %, P < 0.0001). YP were more likely to undergo curative hepatic resection (27% vs. 17 %, P < 0.0001), to receive any chemotherapy (93% vs. 78 % (P < 0.0001), and to receive 3+ lines of chemotherapy (30% vs. 24 % (P < 0.0034)). Median first-line progression free survival (10.2 versus 10.6 months) was similar for YP vs OP, but overall survival (32.1 versus 25.4 months, HR = 0.745, P < 0.0001) was longer in YP. CONCLUSION: Known prognostic variables mostly favored YP versus OP with newly diagnosed mCRC, who were also more heavily treated. Consistent with this, overall survival outcomes were improved. This data does not support that CRC in YP represent a distinct subset of mCRC patients, or that a modified treatment approach is warranted.

The influence of systemic therapy on the serum levels of IL-6 and IL-8 in pemphigus vulgaris.

BACKGROUND: The place of cell-mediated immunity and cytokines in the immunopathogenesis of pemphigus vulgaris (PV) has not been fully established. OBJECTIVE: To assess the serum levels of pro-inflammatory cytokines, Interleukine-6 (IL-6) and Interleukine-8 (IL-8), in PV patients before and after therapy, to evaluate the influence of therapy on the serum cytokine levels. METHODS: Sixty-six newly diagnosed PV patients enrolled into the study. The serum levels of IL-8 and IL-6 were measured in 66 and 64 patients, respectively. According to the extent of skin and mucosal involvement, the patients were divided into two groups namely mild and severe. The serum levels of cytokines were measured using enzyme-linked immunosorbent assay (ELISA) method before and after 4 weeks of prednisolone plus azathioprine therapy. RESULTS: In 64 patients studied for the serum level of IL-6, the median IL-6 level was significantly decreased from 1.6 to 0.9 pg/mL by therapy (P-value = 0.001). Segregating the patients according to the severity of the disease, the serum level of IL-6 did not differ significantly by therapy in patients with a mild disease. However, in patients with a severe disease the median serum level of IL-6 decreased significantly from 1.8 to 0.9 pg/mL after therapy (P-value = 0.001). No significant changes were found in the IL-8 level by treatment. CONCLUSION: The significant decrease in the IL-6 level after therapy suggests that blocking of IL-6 could have therapeutic benefits for the treatment of PV, particularly in severe forms.

Susceptibility to pulmonary tuberculosis in Iranian individuals is not affected by compound KIR/HLA genotype.

Natural killer (NK) cells have distinctive functional capacities that are likely to contribute both to innate and adaptive immunity to Mycobacterium tuberculosis. Killer cell immunoglobulin-like receptors (KIR) and their ligands, i.e. human leukocyte antigen (HLA) class I molecules contribute partly in regulation of NK cell activity. In this study, the impact of compound KIR/HLA genotype on susceptibility to pulmonary tuberculosis (TB) has been evaluated in Iranian individuals. A total of 107 TB patients and 100 matched healthy controls were genotyped for 17 KIR genes and their three major HLA class I ligand groups (-C1, -C2 and -Bw4: -B Bw4(Ile80) , -B Bw4(Thr80) and -A Bw4) by a polymerase chain reaction-sequence-specific primers assay. Various analyses including distribution of KIR and HLA ligand genes and genotypes, frequency of inhibitory and activating KIR+HLA combinations and compound genotype status regarding balance of inhibitory and activating components showed no significant difference between patient and control groups. These findings may suggest that compound KIR/HLA genotype has no major impact on limiting Mycobacterium tuberculosis infection.

Prediction of peritoneal soiling in acute appendicitis with simple clinical and laboratory data. Prospective, multicenter, cohort study of 2,645 adult patients nationwide.

BACKGROUND AND AIMS: In order to facilitate the preoperative prediction of complicated appendicitis, we propose a complementary approach by selecting an endpoint defined by the intraoperative finding of peritoneal soiling (PS). METHODS: Over a 6-month period, 38 centers (5% of all public hospitals) attending emergency general surgery patients on a 24-h, 7-days a week basis, enrolled consecutive adult patients requiring appendectomy. Patients were stratified according to the absence or the finding of PS during the surgical procedure. RESULTS: A total of 2645 patients were included; median age (IQR) was 35 (22-51) years, 44.3% were female. The laparoscopic approach was used in 70.8% of appendectomies. In a third of patients (31.7%), there was PS with pus around the appendix, or bowel contents, free pus, or blood in the peritoneal cavity. To develop the prediction model, 1764 patients were randomly selected for the derivation cohort and the remaining 881 patients were assigned to the validation cohort. On multivariable logistic regression analysis of all patients, two clinical variables (age, and pulse) and three laboratory variables (serum urea, serum sodium, and white blood cell count) were individually associated (P < .05) with a greater probability of having PS (Hosmer-Lemeshow chi, 1.63; P = .99; C-statistic, 0.7). Based on the multivariable regression model, both static and dynamic nomograms were developed for the prediction of PS in patients with acute appendicitis. CONCLUSIONS: The entry of simple clinical and laboratory variables in the dynamic nomogram may be useful in guiding the initial management of patients with acute appendicitis in resource-limited settings.

Initial experience of TAS-102 chemotherapy in Australian patients with Chemo-refractory metastatic colorectal cancer.

For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. This study aims to investigate the efficacy and safety of TAS-102 in a real-world population from Victoria, Australia. A retrospective analysis of prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was undertaken. The characteristics and outcomes of patients receiving TAS-102 were assessed and compared to those enrolled in the registration study (RECOURSE). Across 13 sites, 107 patients were treated with TAS-102. The median age was 60 years (range: 31-83), compared to 63 for RECOURSE. Comparing registry TAS-102-treated and RECOURSE patients, 75% vs 100% were ECOG performance status 0-1, 74% vs 79% had initiated treatment more than 18 months from diagnosis of metastatic disease and 36% vs 49% were RAS wild-type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median progression-free survival (PFS) was 3.3 months compared to 2 months in RECOURSE, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths, where TAS-102 dose at treatment initiation was at clinician discretion.TRACC registry patients treated with TAS-102 were younger than those from the RECOURSE trial, with similar overall survival observed. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS.

KIR3DL1+HLA-B Bw4Ile80 and KIR2DS1+HLA-C2 combinations are both associated with ankylosing spondylitis in the Iranian population.

Contribution of killer cell immunoglobulin-like receptors (KIR) and their human leucocyte antigen (HLA) class I ligands in the pathogenesis of autoimmune diseases has been shown in several studies. In this study, the possible association of KIR genes, their known HLA ligands and compound KIR/HLA genotypes with ankylosing spondylitis (AS) was assessed. Combined KIR/HLA ligand genotyping was performed by a polymerase chain reaction-sequence-specific primers assay in 35 Iranian patients with AS, and genotypes were compared to those in 200 healthy individuals. The frequencies of telomeric cluster genes KIR2DL5A, KIR2DS1 and KIR3DS1 were significantly increased in AS patient group (P(c) = 0.0082, P(c) = 0.0195 and P(c) = 0.0328, respectively). Conversely, HLA-Bw4 ligand (the presence of one or more -B Bw4(Ile80) , -B Bw4(Thr80) and -A Bw4 epitopes) (P(c) = 0.0004) and HLA-B Bw4(Ile80) (P(c) = 0.053) were less frequent in these patients. Meanwhile, compound KIR/HLA genotype analyses revealed lower frequency of KIR3DL1+HLA-B Bw4(Ile80) (P(c) = 0.0343) and higher frequency of KIR2DS1+HLA-C2 (P(c) = 0.0308) combinations in patients with AS than in controls. In addition, the genotypes iKIR+HLA > aKIR+HLA (P(c) = .0308) and iKIR+HLA > aKIR (P(c) = 0.0258) were statistically less common, and genotypes iKIR+HLA = aKIR+HLA (P(c) = 0.0081) and iKIR+HLA < aKIR (P(c) = 0.077) were more common in patient group. Our findings suggest a role for excessive or inappropriate NK cell activation through 'KIR/HLA' system in AS disease.

The effect of the venom of the yellow Iranian scorpion Odontobuthus doriae on skeletal muscle preparations in vitro.

The yellow Iranian scorpion Odontobuthus doriae can cause fatal envenoming, but its mechanism of action is unclear. One of the reported manifestations of envenoming is moderate to severe involuntary tremor of skeletal muscle. In order to understand better the mechanism of action of this venom on skeletal muscle function, we examined the effects of the venom in vitro on chick biventer cervicis (CBC) and mouse hemidiaphragm (MHD) nerve muscle preparations. O. doriae venom (0.3-10mug/ml) initially increased and then decreased twitch height. The venom also caused contracture in both preparations. In mouse triangularis sterni preparations, used for all intracellular recording techniques, the venom enhanced the release of acetylcholine and induced repetitive firing of nerve action potentials and endplate potentials in response to single-shock stimulation. With extracellular recording techniques, scorpion venom (1mug/ml) was found to cause changes to the perineural waveform associated with nerve terminal action potentials consistent with effects on Na(+) and K(+) currents. The main facilitatory effects of O. doriae venom are likely to be due to toxins that affect Na(+) channels in nerve-muscle preparations similar to most Old World scorpion venoms, but blocking effects on K(+) channels are also possible. Such effects could lead to initial enhancement of transmitter release that could underlie the muscle tremors seen in victims. Toxins acting on Na(+) and K+ currents have been isolated from the venom [Jalali, A., Bosmans, F., Amininasab, M., Clynen, E., Cuypers, E., Zaremirakabadi, A., Sarbolouki, M.N., Schoofs, L., Vatanpour, H., Tytgat, J., 2005. OD1, the first toxin isolated from the venom of the scorpion Odontobuthus doriae active on voltage-gated Na(+) channels. FEBS Lett. 579, 4181-4186; Abdel-Mottaleb, Y., Clynen, E., Jalali, A., Bosmans, F., Vatanpour, H., Schoofs, L., Tytgat, J., 2006. The first potassium channel toxin from the venom of the Iranian scorpion Odontobuthus doriae. FEBS Lett. 580, 6254-6258]; however, the muscle paralysis seen at higher concentrations of venom may be due to additional, as yet uncharacterised, components of the venom.

Social media as an open-learning resource in medical education: current perspectives.

PURPOSE: Numerous studies evaluate the use of social media as an open-learning resource in education, but there is a little published knowledge of empirical evidence that such open-learning resources produce educative outcomes, particularly with regard to student performance. This study undertook a systematic review of the published literature in medical education to determine the state of the evidence as to empirical studies that conduct an evaluation or research regarding social media and open-learning resources. METHODS: The authors searched MEDLINE, ERIC, Embase, PubMed, Scopus, and Google Scholar from 2012 to 2017. This search included using keywords related to social media, medical education, research, and evaluation, while restricting the search to peer reviewed, English language articles only. To meet inclusion criteria, manuscripts had to employ evaluative methods and undertake empirical research. RESULTS: Empirical work designed to evaluate the impact of social media as an open-learning resource in medical education is limited as only 13 studies met inclusion criteria. The majority of these studies used undergraduate medical education as the backdrop to investigate open-learning resources, such as Facebook, Twitter, and YouTube. YouTube appears to have little educational value due to the unsupervised nature of content added on a daily basis. Overall, extant reviews have demonstrated that we know a considerable amount about social media use, although to date, its impacts remain unclear. CONCLUSION: There is a paucity of outcome-based, empirical studies assessing the impact of social media in medical education. The few empirical studies identified tend to focus on evaluating the affective outcomes of social media and medical education as opposed to understanding any linkages between social media and performance outcomes. Given the potential for social media use in medical education, more empirical evaluative studies are required to determine educational value.

Diethyl methyl chitosan as an intestinal paracellular enhancer: ex vivo and in vivo studies.

Chitosan exhibits favorable biological properties such as no toxicity, biocompatibility and biodegradability; therefore, it has attracted great attention in both pharmaceutical and biomedical fields. Chitosan exhibits poor solubility at pH values above 6 that prevents enhancing effects at the sites of absorption of drugs. In the present work, N-diethyl methyl chitosan (DEMC) was prepared and the enhancing effect of this polymer was investigated. Ex vivo studies have shown a significant increase in absorption of brilliant blue in the presence of diethyl methyl chitosan in comparison with chitosan. DEMC with positive charges is able to interact with tight junctions of colon epithelial cells and hence increases permeability of brilliant blue across the tight junctions. In vivo investigations have exhibited the absorption enhancer effects of DEMC on the colon absorption of insulin in normal and diabetic rats. The insulin absorption from the rat's colon was evaluated by its hypoglycemic effect. A significant decrease in blood glucose was observed, when mixture of insulin and DEMC was introduced in ascending colon of rats.

Efficiency of allogeneic hematopoietic SCT from HLA fully-matched non-sibling relatives: a new prospect of exploiting extended family search.

The best donors for hematopoietic SCT (HSCT) are fully-matched siblings. In patients without fully-matched siblings, HLA registries or cord blood banks are alternative strategies with some restrictions. Owing to the high rate of consanguineous marriage in our country, between 2006 and 2013, extended family searches were undertaken in Hematology-Oncology Research Center and Stem Cell Transplantation (HORCSCT), Tehran, Iran, in 523 HSCT candidates with parental consanguinity and no available HLA identical sibling. Fully-matched other-relative donors were found for 109 cases. We retrospectively studied the HSCT outcome in these patients. Median time to neutrophil engraftment was 13 days (range: 9-31days). In 83 patients, full chimerism and in 17 patients, mixed chimerism was achieved. Acute GvHD (aGvHD) grade II-IV appeared in 36 patients (33%). The frequency of aGvHD development in various familial subgroups was NS. Five patients expired before day+100. In the surviving 104 cases, chronic GvHD developed in 20 patients (19.2%). The distantly related subgroup had significantly a higher rate of cGvHD (P=0.04). The 2-year OS and disease-free survival (DFS) were 76.7±4.5% and 71.7±4.7%, respectively. No significant difference in OS (P=0.30) and DFS (P=0.80) was unraveled between various familial relationships. Our considerable rate of fully-matched non-sibling family members and the favorable outcome support the rationale for extended family search in regions where consanguineous marriage is widely practiced.

Hematopoietic SCT in Iranian children 1991-2012.

This study presents the pediatric hematopoietic SCT (HSCT) activity in Iran between 1991 and 2012. Overall, 1105 fifteen-year-old or younger patients have undergone HSCT (975 allogeneic and 130 autologous). Annual HSCTs have been increasing steadily since 2007. HLA-matched siblings and other related donors were the main source of HSCs, although since 2008 a national HLA registry has been established to fill the gap for patients lacking a related donor. Inherited abnormalities of RBCs (45.88%), leukemias (27.6%) and BM failure syndromes (11.94%) constituted the majority of HSCTs during this period. Two-year overall survival and disease-free survival rates for all patients were 74.2% (95% confidence interval (CI): 71.6-77) and 66.3% (95% CI: 63.5-69.3), respectively. Leading cause of death in allogeneic group was TRM (165 deaths) and relapse caused the majority of deaths in the autologous group (39 deaths). All HSCTs from the beginning have been performed exclusively with TBI-free-conditioning regimens, which provides unique data for comparison with activities of other centers. Encouraging survival rates provide a basis for future studies on the extensive applicability of TBI-free-conditioning regimens in pediatric HSCT.

Influence of cold ischemia time, pretransplant anti-porcine antibodies, and donor/recipient size matching on hyperacute graft rejection after discordant porcine to cynomolgus kidney transplantation.

Organs transplanted between phylogenetically disparate species, such as from the pig into the primate, are subject to hyperacute rejection (HAR). This form of xenograft rejection is mediated by preformed natural antibodies and is believed to occur invariably in discordant xenografts thus leading to rapid destruction and complete thrombosis of the graft. Recent data, however, have shown that in the porcine to cynomolgus monkey setting, HAR is not inevitably seen after porcine kidney transplantation. The influence of preoperative antiporcine antibody levels in the recipient, cold ischemia time, and donor organ weight on the onset of HAR was investigated by using unmodified large white pigs (aged 3-12 weeks) as organ donors and adult cynomolgus monkeys (aged 1.5-3.5 years) as recipients. Porcine kidney xenotransplantation was performed in either a non-life-supporting model (n=7) or in a life-supporting model (n=8). In both models, no correlation was found between cold ischemia time and HAR. When preoperative anti-porcine antibody levels were investigated, a significant increase in incidence of HAR was observed in animals with elevated anti-porcine IgM (P<0.05) but not IgG levels (P=NS). Interestingly, although 5 of 12 grafts with an organ weight of less than 50 g underwent HAR, none of three grafts with a donor organ weight of more than 70 g showed signs of HAR. In addition, all three larger grafts showed intraoperative and postoperative urine production, although only in 1 (48 g) of the 12 grafts weighing less than 50 g primary graft function was observed. In one animal, a second porcine kidney (23 g) was successfully transplanted (without HAR) immediately after HAR and subsequent removal of a first porcine kidney (20 g). These results indicate that in the porcine to cynomolgus monkey setting anti-porcine IgM rather than IgG anti-porcine antibody levels seem to be of predominant importance for the induction of HAR. By increasing the donor organ size and weight the frequency of the onset of HAR can be at least reduced. This is most likely due to immunoabsorption of the recipients preformed antibodies in the porcine kidney without lethal damage for the graft.

Does leptin cause functional peripheral sympatholysis?

Leptin is a protein produced by adipocytes. Leptin is known to markedly and rapidly increase sympathetic nerve activity to the kidney and hindlimb of experimental animals. Recent studies suggest that leptin may stimulate endothelial production of nitric oxide, which could oppose sympathetically induced vasoconstriction. We tested the hypothesis that such actions of leptin may produce peripheral functional sympatholysis. In Sprague-Dawley rats, we intermittently stimulated the abdominal sympathetic trunk and measured renal and hindlimb blood flows before and after 3 h of infusion of leptin (1000 microg/kg, n = 7) or vehicle (n = 7). Leptin did not change arterial pressure, heart rate, or renal or hindlimb conductance over the course of 3 h. In addition, leptin did not significantly alter sympathetically mediated vasomotor responses to electrical stimulation, as compared with vehicle. Thus, we conclude that leptin does not change regional blood flows, and that leptin also does not appear to have vascular or neural actions to cause peripheral functional sympatholysis.

A primate model for discordant pig to primate kidney xenotransplantation without hyperacute graft rejection.

Organs transplanted between phylogenetically disparate species, such as from the pig into the primate, are subject to intragraft deposition of preformed recipient immunoglobulin M (IgM) antibodies with subsequent complement activation finally leading to complete and rapid destruction of the xenograft (hyperacute graft rejection, HAR). Current therapeutic strategies for abrogation of HAR include pretransplant antibody absorption by specific or nonspecific extracorporeal column perfusion, ex vivo donor organ perfusion, the administration of substances interfering with complement activation, or even the genetic alteration of the donor. Here, in the pig to cynomolgus monkey species combination, we are describing an experimental model for abrogation of HAR by using large, relative to the recipient weight, oversized donor kidneys as xenotransplants. Porcine kidney xenotransplantation (n = 15) was performed using large white pigs of different weights and ages as organ donors and cynomolgus monkeys as recipients. In grafts with an organ weight below 50 g (20 to 48 g, median 25 g), primary nonfunction (PNF) of the porcine kidney was observed in 11 out of 12 cases and complete HAR in 5 out of 12 experiments. In contrast, none of three grafts with a donor organ weight >70 g showed signs of HAR or PNF. In one animal, a second porcine kidney from the same donor (23 g) was successfully transplanted immediately after HAR and subsequent removal of a first porcine kidney (20 g). By using appropriate immunohistochemistry stainings of reperfusion biopsies, profound deposition of recipient natural antibodies in both small and large xenografts was shown, with only scarce deposition of C3 and C5b-9 in the latter, indicating only incomplete intragraft activation of the complement cascade in these organs. Intraoperative cardiac output (CO) measurements performed in 7 experiments demonstrated a 20 to 50% decrease in CO following reperfusion in 6 out of 7 grafts irrespective of the donor organ weight. The intraoperative decrease in CO was not associated with perioperative morbidity or mortality. The use of oversized doner kidneys can enable the study of a variety of immunologic and physiologic sequela beyond HAR associated with life-supporting discordant primate kidney transplantation.

Adaptive Fractional-order Control for Synchronization of Two Coupled Neurons in the External Electrical Stimulation.

This paper addresses synchronizing two coupled chaotic FitzHugh-Nagumo (FHN) neurons with weakly gap junction under external electrical stimulation (EES). To transmit information among coupled neurons, by generalization of the integer-order FHN equations of the coupled system into the fractional-order in frequency domain using Crone approach, the behavior of each coupled neuron relies on its past behavior and the memorized system can be a better fit for the neuron response. An adaptive fractional-order controller based on the Lyaponuv stability theory was designed to synchronize two neurons electrically coupled with gap junction in EES. The proposed controller is also robust to the inevitable random noise such as disturbances of ionic channels. The simulation results demonstrate the effectiveness of the control scheme.

Effect of stage of maturity of grass at harvest on intake, chewing activity and distribution of particle size in faeces from pregnant ewes.

This study was conducted to investigate the effect of stage of maturity at harvest on the intake of grass silage, eating and ruminating activity and the distribution of faecal particle size in ewes during late pregnancy. A total of 18 Swedish Finull x Dorset 85 ± 8 kg (mean 6 ± s.d.) ewes bearing twins were randomly assigned to three dietary treatments 6 weeks before lambing. The treatments included ad libitum feeding with early harvested (EH), medium harvested (MH) or late harvested (LH) primary-growth grass silage with 45%, 58% and 63% NDF on a dry matter (DM) basis, respectively. Intake and chewing activity were recorded and faeces were sampled over 4 continuous days for each individual ewe. The faeces samples were washed in nylon bags, freeze dried and sieved with pore sizes from 2.4mm to 0.1 mm; particles less than 0.1mm in size were also collected. Subsamples of each sieving fraction were scanned and the dimensions of the individual particles in each sieving fraction were measured by image analysis. In addition, the number of particles longer than 7 mm was counted from the particles retained on a sieve with a pore size of 2.4mm using a simple wet sieving technique. The time spent eating and ruminating per kg of DM intake was affected by the stage of maturity at harvest; it was shorter in ewes fed EH compared with ewes fed MH and LH ( P < 0.05). In comparison with feeding LH, feeding EH resulted in the retention of a larger proportion of particles in the lower and upper sieve fractions (< 0.2mm and > 1 mm, respectively, P < 0.01), a smaller mean particle size ( P < 0.05) and a smaller mean particle width in faeces ( P < 0.01). The results from the simple wet sieving technique confirmed the results from dry sieving and image analysis, showing a higher number of large particles in faeces from ewes fed the EH compared with the ewes fed the MH and LH (P < 0.001). In conclusion, the distribution of faecal particle size might be considered as a footprint of the characteristics of forage fibre eaten by ewes.

Traumatic dissecting posterior cerebral artery aneurysm. A case report and review of the literature.

Dissecting posterior cerebral artery (PCA) aneurysms are among rare cerebrovascular malformations accounting for 2% to 6% of all aneurysms. Herein we describe a case of pediatric dissecting aneurysm located in the PCA with documentation of aneurysm development. In addition, we discuss its treatment with a new therapeutic method involving glue injection.