a case of lockjaw in the emergency department

Tetanus with cephalic involvement is not a typical presentation of the disease; characteristic signs and symptoms are strictly localized in cranial district, although it could frequently progress to the classical generalized form. Tetanus is still spread worldwide, especially in particular subgroups as elderly and newborn babies and in countries with an inadequate vaccine coverage.We report a case of an adult man with generalized tetanus with cephalic presentation in Emergency Department. We aim to outline how difficult it was to diagnose in an adult patient without apparent exposition of previous minimal trauma or injury because of a lot of confusing factors and slow progressing clinical signs. Prompt recognition of signs and symptoms, opportune target therapy and supportive care, in association with correct vaccination schedule, are paramount to determine the prognosis for affected patients

The metabolic adaptation evoked by arginine enhances the effect of radiation in brain metastases

Selected patients with brain metastases (BM) are candidates for radiotherapy. A lactatogenic metabolism, common in BM, has been associated with radioresistance. We demonstrated that BM express nitric oxide (NO) synthase 2 and that administration of its substrate l-arginine decreases tumor lactate in BM patients. In a placebo-controlled trial, we showed that administration of l-arginine before each fraction enhanced the effect of radiation, improving the control of BM. Studies in preclinical models demonstrated that l-arginine radiosensitization is a NO-mediated mechanism secondary to the metabolic adaptation induced in cancer cells. We showed that the decrease in tumor lactate was a consequence of reduced glycolysis that also impacted ATP and NAD+ levels. These effects were associated with NO-dependent inhibition of GAPDH and hyperactivation of PARP upon nitrosative DNA damage. These metabolic changes ultimately impaired the repair of DNA damage induced by radiation in cancer cells while greatly sparing tumor-infiltrating lymphocytes.Fil: Marullo, Rossella. Cornell University; Estados UnidosFil: Castro, Monica. Universidad de Buenos Aires; ArgentinaFil: Yomtoubian, Shira. Cornell University; Estados UnidosFil: Nieves Calvo Vidal, M.. Cornell University; Estados UnidosFil: Revuelta, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Krumsiek, Jan. Cornell University; Estados UnidosFil: Nicholas, Andrew P.. Cornell University; Estados UnidosFil: Cresta Morgado, Pablo. Universidad de Buenos Aires; ArgentinaFil: Yang, ShaoNing. Cornell University; Estados UnidosFil: Medina, Vanina Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Roth, Berta María Cristina. Universidad de Buenos Aires; ArgentinaFil: Bonomi, Marcelo. Ohio State University; Estados UnidosFil: Keshari, Kayvan R.. Memorial Sloan Kettering Cancer Center; Estados UnidosFil: Mittal, Vivek. Cornell University; Estados UnidosFil: Navigante, Alfredo Hugo. Universidad de Buenos Aires; ArgentinaFil: Cerchietti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentin

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Tunable radical scavenging activity of carbon nanotubes through sonication

Carbon nanotubes (CNTs) having controlled radical scavenging activity have been achieved tuning the content of their lattice defects induced by an ultra-sound (us) treatment. The reactivity of CNTs, subjected to ultra-sonication for different time intervals, toward 1,1-diphenyl-2-pycryl (DPPH) and hydroxyl (•OH) radicals has been estimated and related to defect concentration, evaluated through Raman spectrometry. The radical scavenging efficiency of ultra-sound treated CNTs (us-CNTs) increases with increasing the content of the structural defects, suggesting that the defect resulting from us treatment can be capitalized to obtain an amplified and controlled radical scavenging activity. The us-CNTs have been incorporated in ultra high molecular weight polyethylene (UHMWPE) matrix by hot compaction with the aim to exploit their anti-oxidant activity against photo- and thermo-oxidative degradation. The us-CNTs containing nanocomposites show progressively improved photo- and thermo-oxidative resistance with increasing the us time, highlighting that the stability of the nanocomposites can be profitably modulated by controlling the amount of CNT structural defect

Evaluation of reactive oxygen metabolites in trigeminal ganglia of \u3b1-herpesvirus seropositive italian mediterranean buffaloes (Bubalus bubalis)

Abstract In nature, herpesviruses are mostly associated with a single host species. Italian Mediterranean buffaloes (Bubalus bubalis) is associated with Bubaline herpesvirus 1 (BuHV-1) but also with Bovine herpesvirus 1 (BoHV-1). Like different alphaherpesvirinae subfamily members, the primary site for BuHV-1 or BoHV-1 latency is sensory neurons within trigeminal ganglia (TG). Recently, it has been shown that cattle infected by BoHV-1 seemed to have more oxidative stress and low antioxidant defense (Durgut et al., 2013). Thus, to better understand the physiopathology of BuHV-1 or BoHV-1 infection in Bubalus bubalis, we collected blood through iugulation and TG after decapitation. Samples from each TG were placed in a single 50-ml conical tube, and the tube were placed in a dry ice ethanol bath. TG samples were then stored at -80\ub0C. Animals submitted for sampling were chosen within the > 5 year age category because considered at higher risk of infection. The presence of antibodies against BuHV-1 or BoHV-1 was investigated in 15 blood samples by enzyme-linked immunosorbent assay (anti-gB/gE blocking ELISA) (Idexx). Through the combined use of gB-gE ELISA tests, we assigned a specific infection status, for the BuHV1 infection status (gB-pos/gE-neg), and for the BoHV1 status (gBpos/gE-pos) as reported by Scicluna et al. (2007). The ELISA results showed that 40% of tested samples was positive at BoHV-1 whereas 33.3% resulted to be BuHV-1 positive. Moreover 26.7% were BoHV-1 and BuHV-1 negative (gB-neg/gE-neg). Furthermore, we examined trigeminal ganglia tissues of the 15 animals. Oxidative status was assessed using the Reactive Oxygen Metabolites-derived compounds (d-ROMs) test and the antioxidant activity (anti-ROMs) test through spectrophotometric procedures. TG of seropositive or seronegative buffaloes were also used to measure the concentration of lipid peroxides using the Lipotiss test. We detected in TG of seropositive BuHV-1 animals a significantly reduction of d-ROMs values (P < 0.001) as well as anti-ROMs values (P < 0.001) compared with those in TG of seronegative animals. Whereas TG of seropositive BoHV-1 animals had significantly higher d-ROMs values (P < 0.001) and lower anti-ROMs values (P < 0.001) compared with those in TG of seronegative animals. Furthermore, the results of lipotiss test showed that samples of both seropositive BuHV-1 and BoHV-1 animals were significantly lower (P <0.001; P < 0.01) compared with those of seronegative animals. Taken together, our preliminary results suggest that oxidative stress pattern and oxidative defence barrier are altered in latently infected TG compared with control uninfected TG. In particular, our results suggest that the presence of BuHV-1, virus species-specific, seems to induce a worsening balance in ROMs levels. Future studies are needed in order to assess the prognostic role of oxidative stress in trigeminal ganglia of Bubalus bubalis

EVALUATION OF REACTIVE OXYGEN METABOLITES IN TRIGEMINAL GANGLIA OF ALPHAHERPESVIRUS SEROPOSITIVE ITALIAN MEDITERRANEAN BUFFALOES (BUBALUS BUBALIS)

In nature, herpesviruses are mostly associated with a single host species. Italian Mediterranean buffaloes (Bubalus bubalis) is associated with Bubaline herpesvirus 1 (BuHV-1) but also with Bovine herpesvirus 1 (BoHV-1). Like different alphaherpesvirinae subfamily members, the primary site for BuHV-1 or BoHV-1 latency is sensory neurons within trigeminal ganglia (TG). Recently, it has been shown that cattle infected by BoHV-1 seemed to have more oxidative stress and low antioxidant defense (Durgut et al., 2013). Thus, to better understand the physiopathology of BuHV-1 or BoHV-1 infection in Bubalus bubalis, we collected blood through iugulation and TG after decapitation. Samples from each TG were placed in a single 50-ml conical tube, and the tube were placed in a dry ice ethanol bath. TG samples were then stored at -80°C. Animals submitted for sampling were chosen within the > 5 year age category because considered at higher risk of infection. The presence of antibodies against BuHV-1 or BoHV-1 was investigated in 15 blood samples by enzyme-linked immunosorbent assay (anti-gB/gE blocking ELISA) (Idexx). Through the combined use of gB-gE ELISA tests, we assigned a specific infection status, for the BuHV1 infection status (gB-pos/gE-neg), and for the BoHV1 status (gB-pos/gE-pos) as reported by Scicluna et al. (2007). The ELISA results showed that 40% of tested samples was positive at BoHV-1 whereas 33.3% resulted to be BuHV-1 positive. Moreover 26.7% were BoHV-1 and BuHV-1 negative (gB-neg/gE-neg). Furthermore, we examined trigeminal ganglia tissues of the 15 animals. Oxidative status was assessed using the Reactive Oxygen Metabolites-derived compounds (d-ROMs) test and the antioxidant activity (anti- ROMs) test through spectrophotometric procedures. TG of seropositive or seronegative buffaloes were also used to measure the concentration of lipid peroxides using the Lipotiss test. We detected in TG of seropositive BuHV-1 animals a significantly reduction of d- ROMs values (P < 0.001) as well as anti-ROMs values (P < 0.001) compared with those in TG of seronegative animals. Whereas TG of seropositive BoHV-1 animals had significantly higher d-ROMs values (P < 0.001) and lower anti-ROMs values (P < 0.001) compared with those in TG of seronegative animals. Furthermore, the results of lipotiss test showed that samples of both seropositive BuHV-1 and BoHV-1 animals were significantly lower (P < 0.001; P < 0.01) compared with those of seronegative animals. Taken together, our preliminary results suggest that oxidative stress pattern and oxidative defence barrier are altered in latently infected TG compared with control uninfected TG. In particular, our results suggest that the presence of BuHV-1, virus species-specific, seems to induce a worsening balance in ROMs levels. Future studies are needed in order to assess the prognostic role of oxidative stress in trigeminal ganglia of Bubalus bubalis

Relations between serum reactive oxygen metabolites and alphaherpesvirus infection in Italian Mediterranean buffaloes - Bubalus bubalis

Introduction: In recent years, oxidative stress has been postulated to be an important factor in pathogenesis and development of diseases. Reactive Oxygen Species (ROS) are well known for being both beneficial and deleterious and have long been known to be a component of the killing response of immune cells to microbial invasion. Measuring the free radical activity in serum samples is the best way to investigate the association between oxidative stress and infectious diseases. The aim of this study is to determine the association between alphaherpesvirus infection and serum reactive oxygen metabolites (ROM) in Italian Mediterranean buffaloes (Bubalus bubalis). Materials and Methods: The presence of antibodies against bovine herpesvirus type 1 (BoHV-1) or bubaline herpesvirus type 1 (BuHV-1) was investigated by enzyme-linked immunosorbent assay (anti- gB/gE blocking ELISA) (Idexx). We carried out the derivatives of ROM (d-ROM) and the antioxidant activity (anti-ROM) tests by spectrophotometry in sera of BoHV-1 (A) or BuHV-1 (B) infected animals compared to seronegative animals (C). Results: The concentrations of d-ROM in the three groups, expressed in Carratelli Units (U-CARR) were, respectively, 64.6 \ub1 11.6, 85.0 \ub1 10.7 and 56.2 \ub1 10.5. Although the serum d-ROM levels in group A and B were higher than that in group C, only the group B compared with the control group C was significant at p < 0.05. At anti-ROM test, the three groups of animals showed values respectively of: 287.5 \ub1 66.1, 318 \ub1 64.3 and 276 \ub1 53.0. The results of group A and B compared to that of control group C were not significant. The oxidative stress index (OSI), calculated as d-ROM/anti-ROM x 100, showed significant differences between the groups B (26) and C (20) whereas no significant difference was detected between the groups A (22) and C (20). Discussion and Conclusions: Our data indicate that in alphaherpesvirus infected buffaloes, in particular those in BuHV-1 infected, the d-ROM and the OSI values were significantly increased. These results suggest that the presence of BuHV-1, the virus species-specific, seems to induce a worsening balance in ROM levels, whereas that of BoHV-1 has no substantial effects. Future studies are needed to assess the role of oxidative stress in Bubalus bubalis infected by alphaherpesvirus

Metabolomic Profiling Reveals Cellular Reprogramming of B-Cell Lymphoma by a Lysine Deacetylase Inhibitor through the Choline Pathway

Despite the proven clinical antineoplastic activity of histone deacetylase inhibitors (HDACI), their effect has been reported to be lower than expected in B-cell lymphomas. Traditionally considered as “epigenetic drugs”, HDACI modify the acetylation status of an extensive proteome, acting as general lysine deacetylase inhibitors (KDACI), and thus potentially impacting various branches of cellular metabolism. Here, we demonstrate through metabolomic profiling of patient plasma and cell lines that the KDACI panobinostat alters lipid metabolism and downstream survival signaling in diffuse large B-cell lymphomas (DLBCL). Specifically, panobinostat induces metabolic adaptations resulting in newly acquired dependency on the choline pathway and activation of PI3K signaling. This metabolic reprogramming decreased the antineoplastic effect of panobinostat. Conversely, inhibition of these metabolic adaptations resulted in superior anti-lymphoma effect as demonstrated by the combination of panobinostat with a choline pathway inhibitor. In conclusion, our study demonstrates the power of metabolomics in identifying unknown effects of KDACI, and emphasizes the need for a better understanding of these drugs in order to achieve successful clinical implementation