A comparative study of intravenous lignocaine, dexamethasone and combination of lignocaine-dexamethasone in attenuating propofol induced pain

Background: General anesthesia is preferred during surgeries to reduce the pain stimuli in patients and to increase the precision of surgical procedure. Propofol is amongst the most widely used general anesthetic agent with limitation of induced pain during administration. Current study was conducted to compare the effect of intravenous pre-administration of various drugs in attenuating propofol induced pain. Methods: A comparative observational study was conducted on patients of either sex and aged between 18-60 years. Patients were divided in three groups, who received intravenous lignocaine, dexamethasone and combination of lignocaine-dexamethasone respectively to attenuate propofol induced pain. Different variables like HR, SBP, DBP, MAP, RR SpO2 and any adverse events were monitored in all the patients. Results: The 46.66% and 53.33% patients who received lignocaine and dexamethasone alone perceived propofol induced mild to moderate pain; while only 23.33% patients who received lignocaine and dexamethasone in combination perceived mild propofol induced pain. The propofol induced pain event was persistent in only 2 out of 30 patients after a time lapse of 30 seconds for the group receiving lignocaine and dexamethasone in combination. Whereas, the pain event was present even after time lapse of 30 seconds in 08 and 07 out of 30 patients of groups receiving lignocaine and dexamethasone alone.Conclusions: Pre-administration of lignocaine and dexamethasone in combination attenuated the propofol induced pain more significantly in comparison to single administration of mentioned drugs. No significant adverse events except perianal irritation were observed in some patients who received combination of lignocaine and dexamethasone intravenously.

Comparative Evaluation of Immune Responses and Protection of Chitosan Nanoparticles and Oil-Emulsion Adjuvants in Avian Coronavirus Inactivated Vaccines in Chickens

Efficient vaccines are the main strategy to control the avian coronavirus (AvCoV), although several drawbacks related to traditional attenuated and inactivated vaccines have been reported. These counterpoints highlight the importance of developing new alternative vaccines against AvCoV, especially those able to induce long-lasting immune responses. This study evaluated and compared two inactivated vaccines formulated with AvCoV BR-I variants, one composed of chitosan nanoparticles (AvCoV-CS) and the second by Montanide oily adjuvant (AvCoV-O). Both developed vaccines were administered in a single dose or associated with the traditional Mass attenuated vaccine. The AvCoV-CS vaccine administered alone or associated with the Mass vaccine was able to induce strong humoral and cell-mediated immune (CMI) responses and complete protection against IBV virulent infection, wherein single administration was characterized by high IgA antibody levels in the mucosa, whereas when associated with the Mass vaccine, the serum IgG antibody was predominantly observed. On the other hand, single administration of the oily vaccine presented poor humoral and CMI responses and consequently incomplete protection against virulent challenge, but when associated with the Mass vaccine, immune responses were developed, and complete protection against infection was observed. Both of our experimental vaccines were able to induce full protection against virulent IBV challenge. A single dose of AvCoV-CS vaccine was sufficient to achieve complete protection, while AvCoV-O required a previous priming by a Mass strain to complete the protection.

Repeated intravenous infusion of mesenchymal stem cells for enhanced functional recovery in a rat model of chronic cerebral ischemia

OBJECTIVE Stroke is a major cause of long-term disability, and there are few effective treatments that improve function in patients during the chronic phase of stroke. Previous research has shown that single systemic infusion of mesenchymal stem cells (MSCs) improves motor function in acute and chronic cerebral ischemia models in rats. A possible mechanism that could explain such an event includes the enhanced neural connections between cerebral hemispheres that contribute to therapeutic effects. In the present study, repeated infusions (3 times at weekly intervals) of MSCs were administered in a rat model of chronic stroke to determine if multiple dosing facilitated plasticity in neural connections. METHODS The authors induced middle cerebral artery occlusion (MCAO) in rats and, 8 weeks thereafter, used them as a chronic stroke model. The rats with MCAO were randomized and intravenously infused with vehicle only (vehicle group); with MSCs at week 8 (single administration: MSC-1 group); or with MSCs at weeks 8, 9, and 10 (3 times, repeated administration: MSC-3 group) via femoral veins. Ischemic lesion volume and behavioral performance were examined. Fifteen weeks after induction of MCAO, the thickness of the corpus callosum (CC) was determined using Nissl staining. Immunohistochemical analysis of the CC was performed using anti-neurofilament antibody. Interhemispheric connections through the CC were assessed ex vivo by diffusion tensor imaging. RESULTS Motor recovery was better in the MSC-3 group than in the MSC-1 group. In each group, there was no change in the ischemic volume before and after infusion. However, both thickness and optical density of neurofilament staining in the CC were greater in the MSC-3 group, followed by the MSC-1 group, and then the vehicle group. The increased thickness and optical density of neurofilament in the CC correlated with motor function at 15 weeks following induction of MCAO. Preserved neural tracts that ran through interhemispheric connections via the CC were also more extensive in the MSC-3 group, followed by the MSC-1 group and then the vehicle group, as observed ex vivo using diffusion tensor imaging. CONCLUSIONS These results indicate that repeated systemic administration of MSCs over 3 weeks resulted in greater functional improvement as compared to single administration and/or vehicle infusion. In addition, administration of MSCs is associated with promotion of interhemispheric connectivity through the CC in the chronic phase of cerebral infarction.

Infectious complications related to radiofrequency ablation of liver tumors: The role of antibiotics

Background and aim Prophylactic administration of antibiotics within 24 hours of surgery is recommended to reduce the risk of infection. We conducted a prospective study to compare the efficacy of single administration of antibiotics with a historical control of continuous administration of antibiotics for radiofrequency ablation (RFA) of malignant liver tumors. Methods Between February 1, 1999 and November 30, 2010, a total of 6,763 RFA treatments were performed in 2,355 patients, using a protocol with continuous administration of prophylactic antibiotics. On December 1, 2010, we began using a revised protocol with a single administration of prophylactic antibiotics, while continuing to use the old continuous administration protocol for patients who declined the new protocol. Interim analysis was performed to assess the safety of the single administration protocol. Thereafter, from April 1, 2012, all patients were treated using the new protocol. Risk factors for infectious complications of RFA were assessed using logistic regression. Results From December 2010 to March 2012, 766 RFA treatments were performed in 663 patients using the new antibiotic protocol. Infectious complications were observed following 4 of these treatments (0.52%). As the upper limit of the confidence interval (CI) resulting from a one-sided binomial test was exactly the prespecified limit of 1.0%, from April 2012 onwards, we treated all patients using the new protocol with single administration of prophylactic antibiotics. A total of 3,547 RFA treatments were performed using the single administration protocol. Univariable logistic regression indicated that prior transcatheter arterial chemoembolization (TACE) and maximal tumor diameter were significant risk factors for infectious complications (P = 0.04 and P < 0.001, respectively). Multivariable analysis indicated that the adjusted hazard ratio of single vs. continuous administration of antibiotics was 1.20 (95% CI: 0.53–2.75; P = 0.66). Conclusions The rate of infectious complications related to RFA was acceptably low. Single administration of prophylactic antibiotics did not significantly increase the rate of infectious complications related to RFA, compared with a more intensive antibiotic protocol.

Anti-CD37 Alpha-Amanitin Conjugated Antibodies As Therapeutic Weapons for Richter's Syndrome

The leukocyte surface antigen CD37 (TSPAN26), a member of the tetraspanin superfamily, is widely expressed on most malignant B cells, making it an actionable target for treatment of patients with chronic lymphocytic leukemia (CLL) and other B-cell non-Hodgkin lymphoma (NHL) indications. Accordingly, αCD37 antibodies have shown promising results in phase 1/2 clinical trials for CLL and NHL. Richter's syndrome (RS) is the transformation of CLL into an aggressive and rapidly fatal lymphoma, typically a diffuse large B cell lymphoma (DLBCL). RS is a challenging disease since very few effective treatment options exist for these patients and the available regimens, mainly based on R-CHOP scheme, show limited efficacy. We recently established patient-derived xenograft (PDX) models from RS patients and have shown that they can be used to test the efficacy of novel drugs and drug combinations 1,2. All available RS-PDX models were characterized by high-levels of CD37 expression, when assessed by RNA sequencing, reverse-transcriptase-polymerase chain reaction (RT-PCR), flow cytometry (FACS), western blot (WB) and immunohistochemistry (IHC). More precisely, two models (RS1316 and IP867/17) showed slightly higher CD37 levels compared to the others (RS9737 and RS1050). These models were used to test three different αCD37-ATACs®, ADCs which comprise amanitin-derivatives as payload. Amanitin (the main poison in the green deathcap mushroom) belongs to the well-known amatoxin family. Amanitin is taken up by OATP1B3 transporter, solely expressed on hepatocytes. Upon mushroom intoxication, it can lead to severe liver toxicity by inhibiting the RNA polymerase II. Upon conjugation to target-specific antibodies, the maximal tolerated dose is significantly increased by reducing the non-specific liver uptake. By binding to its antigen, ATACs deliver amanitin only into target-positive cancer cells while target negative cells show no off-target toxicity. Consistent with CD37 expression on the cell surface, ex-vivo treatment of freshly purified cells from RS-PDX tumor masses to αCD37-ATACs® resulted in increased apoptosis after 72 hours of treatment, with only minor differences among the 3 ATACs® and the models used. Since alpha-amanitin is a deadly toxin known to target human RNA polymerase II and, at high doses, also RNA polymerase III, we checked messenger RNA levels in basal conditions and after CD37-ATAC® treatment by looking at different housekeeping genes, and confirmed a reduction in global mRNA levels. αCD37-ATAC® efficacy was then assessed in vivo in systemic RS-PDX models where RS cells are intra-venously (i.v.) injected in the tail vein and cells distribute to different tissues (blood, spleen and bone marrow), resembling the human disease. Cells from RS1316, RS1050 and RS9737 models were injected into the tail vein and left to engraft 14 days, before mice were randomly assigned to vehicle or ATAC® groups. A single i.v. treatment for each αCD37-ATAC® was administered, testing two different doses for each compound, and mice were then monitored for survival. Overall, the single administration of all three ATACs® caused highly significant disease regression. In the RS1316 model, independently of the dose or tested ATAC®s, all treated mice, except one, were alive and disease-free until the end of the experiment, 140 days post cells injection, while survival of vehicle-treated mice was 65 days. FACS analysis to trace neoplastic cells in parenchymatous organs and bone marrow confirmed the absence of neoplastic cells. In the other 2 models, RS9737 and RS1050, even though ATAC® treatment did not result in complete disease eradication, a single administration of αCD37-ATAC® resulted in a dramatically increased survival (approximately 35-60 days, depending on the model and ATAC® used). Finally, CD37 expression was confirmed by RNA sequencing on a cohort of 15 primary RS samples, even though with variable levels. Compared to CLL cells, RS samples showed CD37 expression levels comparable to those reported for DLBCL cells. Overall, these data indicate CD37 as a potential target to treat RS patients with selective targeting αCD37-ATACs®. ATACs® is a registered trade mark of Heidelberg Pharma Research GmbH, Germany References Vaisitti T et al. Blood. 2021;137(24):3365-3377. Iannello A, et al. Blood. 2021;137(24):3378-3389. Disclosures Orlik: Heidelberg Pharma: Current Employment. Kulke: Heidelberg Pharma: Current Employment. Pahl: Heidelberg Pharma: Current Employment. Deaglio: Heidelberg Pharma: Research Funding; Astra Zeneca: Research Funding.

Cardiotoxic effect of bleomycin with a single administration in the experiment

The aim of the study was to evaluate the effect of a single injection of bleomycin on the heart Material and methods. The study was conducted in the Research Institute of Transport Medicine during 2016-2021. The experimental model of the cardiotoxic effect of the bleomycin was performed using the medication "Bleocin" manufactured by Nippon Kayaku Co., Ltd. (Japan). According to the task, the study was performed on 10 mature rats of both sexes of the Wistar line with a body weight of 237 ± 20 g. Rats were housed in standard vivarium conditions of Odessa National Medical University. Animals were divided into 2 groups: experimental group (n = 5) and control (n = 5). Bleomycin animals of the experimental group were obtained intraperitoneally at a dose of 0.5 IU / kg once. Withdrawal of animals from the experiment was performed on the 5th day of the experiment, followed by morphological and morphometric examination. Statistical processing of the obtained data was performed by methods of variance, correlation and regression analysis using Statistica 14.0 software (TIBCO, USA) Results. Single administration os bleomycin causes changes in macroscopic parameters (myocardial weight, visual changes) are minimal. The main changes at the microscopic level are represented by contractural degeneration with segmental and / or partial-lateral lysis, ie there is not total but partial myocardial damage. Conclusion. A single injection of bleomycin can cause inflammatory-dystrophic changes of the myocardium.

An Ultrapotent Neutralizing Bispecific Antibody with Broad Spectrum Against SARS-CoV-2 Variants

Some variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are threatening our global efforts of herd immunity, novel and more efficacious agents are urgently needed. We have developed a bispecific antibody, 2022, which bonds with high affinity to two non-overlapping epitopes on the receptor-binding domain (RBD) simultaneously, blocks the binding of RBD to human angiotensin-converting enzyme 2 (ACE2), and potently neutralizes SARS-CoV-2 and all of the variants tested, including variants carrying mutations known to resist neutralizing antibodies approved under Emergency Use Authorization (EUA) and reduce the efficacy of existing vaccines. In a mouse model of SARS-CoV-2, 2022 showed strong prophylactic and therapeutic effects. A single administration of 2022 completely protected all mice from bodyweight loss, as compared with up to 20% loss of bodyweight in placebo treated mice, reduced the lung viral titers to undetectable in all mice treated with 2022 either prophylactically or therapeutically, as compared with around 1X105 pfu/g lung tissue in placebo treated mice. In summary, bispecific antibody 2022 showed potent binding and neutralizing activity across a variety of SARS-CoV-2 variants and could be an attractive weapon to combat the ongoing waves of the COVID-19 pandemic.