Neurotoxicity in operating room personnel working with gaseous and nongaseous anesthesia

Occupational exposure to high concentrations of anesthetic gases (more than 500 ppm of nitrous oxide and more than 15 ppm of halothane and enflurane) can cause neurobehavioral effects in operating room personnel. Factors such as stress and work organization play an additional role in reducing performance capacities. It is still unclear whether these conditions may become the predominant factor in behavioral impairment when exposure to anesthetic gases is reduced; in addition, we wished to ascertain the extent of neurobehavioral and neuroendocrine effects at relatively low levels of exposure to such gases. Therefore the same group of 30 operating room personnel was examined with neurobehavioral tests during gaseous and nongaseous anesthesia. In this way, the neuropsychological performance was examined under the same stress conditions, but with different exposure levels to anesthetic gases. Serum cortisol was measured as an additional biological stress indicator. Prolactin secretion was examined to study possible interference of anesthetic gases with the dopaminergic system. The results were compared with those in a control group of 20 hospital workers from other departments, with similar characteristics in respect of age, sex, and education. During work with gaseous anesthesia, average airborne concentrations (geometric mean) of nitrous oxide were 50.9 ppm (SD 20.8) on the first day of the working week and 54.2 ppm (SD 22.1) on the last day of the working week, whereas average urinary nitrous oxide (geometric mean) were 21.54 g/l on the first day of the working week and 25.67 g/l on the last day of the working week. The operating room workers showed slower reaction times at the end of the week with gaseous anesthesia, compared with workers using nongaseous anesthesia and the control group. At the same time they also showed increased secretion of prolactin, whereas cortisol remained unchanged. Therefore, it can be concluded that lower levels of exposure to anesthetic gases (and not only high exposure levels) cause an impairment of neurobehavioral performance, with the action of stress being less relevant. The mechanism of anesthetics' neurotoxic action seems to be related to interference with the dopaminergic system.     

Expression of her-2/neu on acute lymphoblastic leukemias: implications for the development of immunotherapeutic approaches.

Her-2/neu is a tumor-associated antigen that is expressed on several adenocarcinomas and correlates with poor prognosis. In a previous study (H. J. Bühring et al., Blood, 86: 1916-1923, 1995), it has been demonstrated that Her-2/neu expression can be detected on blast cells from patients with hematological malignancies including acute lymphoblastic leukemia (ALL). Here, we show that Her-2/neu-specific CTLs induced in vitro using peptide-pulsed dendritic cells efficiently lyse primary ALL blasts constitutively expressing both Her-2/neu and human leukocyte antigen A2 in an antigen-specific and MHC-restricted manner. Furthermore, we analyzed the feasibility of this approach in an autologous setting and induced Her-2/neu-specific CTLs using dendritic cells generated from peripheral blood mononuclear cells from an ALL patient that were pulsed with peptides or transfected with in vitro-transcribed Her-2/neu mRNA. Our data demonstrate that Her-2/neu could be used as a potential target for the application of Her-2/neu-directed treatment strategies in ALL including vaccination approaches.     

Prevalence of carpal tunnel syndrome in workers executing complex tasks with the upper extremities

In 50 female workers of a manufacturing plant employed on the assembly line of metal and plastic products with cloth covering, we found a high prevalence of Carpal Tunnel Syndrome (16 cases, 32%, 5 of whom had already undergone surgical treatment). The subjects with positive diagnosis of Carpal Tunnel Syndrome also had a longer occupational exposure to repetitive movements, compared to the other subjects. Among the subjects with this disorder, the length of exposure was also significantly associated with the reported symptoms and the extension threshold measured on the 2nd finger of the dominant hand. Ergonomic assessment of the assembly lines revealed high-frequency repetitive movements and application of force, with insufficient rest intervals.     

Detection of alkaline sphingomyelinase activity in human stool: proposed role as a new diagnostic and prognostic marker of colorectal cancer.

OBJECTIVES: Intestinal alkaline sphingomyelinase, by exerting a major role in dietary sphingomyelin digestion, is responsible for the generation of messengers able to trigger the rapid turnover and apoptosis in intestinal epithelial cells. Markedly reduced mucosal alkaline sphingomyelinase activity has been associated with human colorectal neoplasms. The aim of this study was to analyze the alkaline sphingomyelinase activity in feces from healthy subjects and colorectal adenocarcinoma patients and to correlate it with the enzyme activity in intestinal tissues. MATERIALS AND METHODS: The enzyme activity was measured both in the intestinal samples from 12 healthy controls and 51 patients with colorectal adenocarcinoma (tumoral and paratumoral tissue) and in the fecal samples of 34 healthy subjects and 29 patients with adenocarcinoma. The relation between sphingomyelinase activity and Dukes' stage, cell differentiation degree, age, and gender was also analyzed. RESULTS: Alkaline sphingomyelinase was significantly decreased (P < 0.001; mean reduction >90%) in tumoral intestinal mucosa of patients compared with controls independently of Dukes' stage and tumor differentiation grade. Interestingly, the enzyme activity in histologically normal paratumoral tissues was statistically lower than control samples (P < 0.001). As occurs in neoplastic tissues, a relevant mean reduction (P < 0.0001; almost 90%) of alkaline sphingomyelinase was revealed in stool samples from tumor patients when compared with controls. CONCLUSION: These findings may have implications for cancer biology and perhaps also for the design of clinical test, thus suggesting that the fecal sphingomyelinase activity could really reflect the human intestinal mucosa enzyme level and could represent a new marker for human colorectal adenocarcinoma, mainly taking into account its early appearance in intestinal neoplasms.     

Cooperative cytotoxicity of proteasome inhibitors and tumor necrosis factor-related apoptosis-inducing ligand in chemoresistant Bcl-2-overexpressing cells.

PURPOSE: Bcl-2 overexpression is frequently detected in lymphoid malignancies, being associated with poor prognosis and reduced response to therapy. Here, we evaluated whether Bcl-2 overexpression affects the cytotoxic activity of proteasome inhibitors taken alone or in association with conventional anticancer drugs or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). EXPERIMENTAL DESIGN: Jurkat cells engineered to overexpress Bcl-2 were treated with proteasome inhibitors (MG132, epoxomicin, and bortezomib), anticancer drugs (etoposide and doxorubicin), TRAIL, or combinations of these compounds. Cell death and loss of mitochondrial transmembrane potential were detected by flow cytometry. Cytosolic relocalization of cytochrome c and SMAC/Diablo, caspase cleavage, and Bcl-2 and Mcl-1 levels were determined by immunoblotting. Nuclear factor-kappaB inhibition was done by retroviral transduction with a dominant-negative mutant of IkappaBalpha. RESULTS: Bcl-2 overexpression results in significant inhibition of apoptosis in response to proteasome inhibitors, antiblastics, and TRAIL. Addition of TRAIL to proteasome inhibitors results in a synergistic cytotoxic effect in Bcl-2-overexpressing cells, whereas this result is not reproduced by the combination of proteasome inhibitors with antiblastic drugs. Importantly, proteasome inhibitors plus TRAIL induce mitochondrial dysfunction irrespective of up-regulated Bcl-2. Bcl-2 cleavage to a fragment with putative proapoptotic activity and elimination of antiapoptotic Mcl-1 may both play a role in proteasome inhibitors-TRAIL cooperation. Conversely, nuclear factor-kappaB inhibition by proteasome inhibitors is per se insufficient to explain the observed synergy. CONCLUSIONS: Combined proteasome inhibitors and TRAIL overcome the apoptotic threshold raised by Bcl-2 and may prove useful in the treatment of chemoresistant malignancies with up-regulated Bcl-2.     

Dantrolene protects hippocampal cells from damage induced by TsTX, an alpha-scorpion toxin from Tityus serrulatus.

We examined the effects of dantrolene, an inhibitor of intracellular calcium release, on alterations associated with the intrahippocampal injection of the TsTX scorpion toxin. Male Wistar rats (230-250 g) were injected with Ringer solution (1 microl; n = 6); TsTX toxin (1 microg/microl; n = 8); and dantrolene (10.0 mg/kg) plus TsTX toxin (1 microg/microl; n = 6). After injection, electroencephalographic (EEG) recordings and observation of animals behaviour were performed continuously for 4 h. One week later, animals were submitted to histopathological analysis. TsTX caused electrographic seizure expressed by moderate or intense discharges and neuronal loss in hippocampal areas in all injected animals (n = 8). Dantrolene reduced the effect of TsTX. Thus, 67% of rats (four out of six) treated with toxin and dantrolene had electrographic convulsions, but only for 30 min after injection and none of them presented neuronal damage. Dantrolene or Ringer had no effects on the EEG.     

Emergence and Spread of SARS-CoV-2 Lineages B.1.1.7 and P.1 in Italy

Italy’s second wave of SARS-CoV-2 has hit hard, with more than three million cases and over 100,000 deaths, representing an almost ten-fold increase in the numbers reported by August 2020. Herein, we present an analysis of 6515 SARS-CoV-2 sequences sampled in Italy between 29 January 2020 and 1 March 2021 and show how different lineages emerged multiple times independently despite lockdown restrictions. Virus lineage B.1.177 became the dominant variant in November 2020, when cases peaked at 40,000 a day, but since January 2021 this is being replaced by the B.1.1.7 ‘variant of concern’. In addition, we report a sudden increase in another documented variant of concern—lineage P.1—from December 2020 onwards, most likely caused by a single introduction into Italy. We again highlight how international importations drive the emergence of new lineages and that genome sequencing should remain a top priority for ongoing surveillance in Italy.     

Comments on potential efficacy of monthly administrations of spot-on moxidectin 2.5 %/imidacloprid 10 % in the simultaneous prevention of major canine filarioses

Information on the efficacy of pharmaceutical protocols for the prevention of the major canine filarioses (i.e., Dirofilaria immitis, Dirofilaria repens, and Acanthocheilonema reconditum) under natural conditions is scant. Chemoprophylaxis for canine filarioses under field conditions deserves to be studied more fully and information about vector biology, ecology, and seasonality has to be well appreciated to correctly set control protocols. It is advisable that researchers planning field trials to assess the efficacy of any product for the prevention of canine vector-borne diseases should consider different eco-epidemiological aspects of diseases, including their dynamics of transmission, which are driven by complex interactions between animals, pathogens, and vectors.