Low Dose Pig Anti-Influenza Virus Monoclonal Antibodies Reduce Lung Pathology but Do Not Prevent Virus Shedding

We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing the therapeutic potential of monoclonal antibodies (mAbs). In this study we demonstrated that prophylactic intravenous administration of 15 mg/kg of porcine mAb pb18, against the K160–163 site of the hemagglutinin, significantly reduced lung pathology and nasal virus shedding and eliminated virus from the lung of pigs following H1N1pdm09 challenge. When given at 1 mg/kg, pb18 significantly reduced lung pathology and lung and BAL virus loads, but not nasal shedding. Similarly, when pb18 was given in combination with pb27, which recognized the K130 site, at 1 mg/kg each, lung virus load and pathology were reduced, although without an apparent additive or synergistic effect. No evidence for mAb driven virus evolution was detected. These data indicate that intravenous administration of high doses was required to reduce nasal virus shedding, although this was inconsistent and seldom complete. In contrast, the effect on lung pathology and lung virus load is consistent and is also seen at a one log lower dose, strongly indicating that a lower dose might be sufficient to reduce severity of disease, but for prevention of transmission other measures would be needed.

Haemato-biochemical and blood gas changes in bovines under multimodal anaesthesia

The study was conducted in six crossbred female cattle aged nine months to five years and weighing between 82-375 kg, to evaluate haematobiochemical and blood gas changes in during multimodal general anaesthesia. The animals were premedicated by intravenous administration of butorphanol (0.05mg/kg body weight) immediately followed by xylazine (0.02 mg/kg body weight). On achieving sedation, the animals were controlled in left lateral recumbency and induction of anaesthesia was carried out by intravenous administration of ketamine and midazolam at the dose rate of 4.0 and 0.2 mg/kg body weight respectively. Endotracheal intubation was performed and maintenance of general anaesthesia was carried out using isoflurane in 100% oxygen. The variation in total erythrocyte count, total leukocyte count, volume of packed red cells, platelet count and haemoglobin were non-significant before and after anaesthesia. A non-significant lymphocytopaenia with neutrophilia and mild variations in aspartate aminotransferase and alanine aminotransferase enzyme levels were also noticed. Blood pH reduced significantly (p<0.05) after induction of anaesthesia and returned to baseline values after recovery whereas PvCO2 (p<0.05) and base excess (p<0.01) values increased significantly after induction of anaesthesia. The blood bicarbonate did not alter significantly following induction of anaesthesia.

Oxycodone 5 Miligram is More Effective Than Ketorolac 30 Miligram in Suppressing Cortisol Levels During General Anesthesia

Background: Preemptive analgesia is a developing clinical concept, which involves administering analgesics before pain stimulation occurs, to prevent the sensitization of the nervous system to further stimuli that can cause pain. Ketorolac has strong analgesic properties oxycodone is a semisynthetic opioid that is synthesized from the alkaloid thebaine opiate. Pain could induce stress hormone such as cortisol. Study to compare ketorolac and oxycodone with cortisol has not been investigated. This study aimed to assess intravenous administration of ketorolac 30 mg compared with intravenous 5 mg oxycodone for pain as measured by cortisol levels post-intervention in surgery performed under general anesthesia. Method: A study randomized controlled trial in double-blind form for patients at dr. Mohammad Hoesin Palembang, who will undergo elective surgery with general anesthesia at the Central Surgical Installation building, with the period September-October 2020. There are 24 study samples, to anticipate dropouts, an added sample size is 10%, so the sample size is 26 for each treatment group. The selection of subjects according to the purpose of the study was carried out by simple random. Data analysis using SPSS ver 22.0 software. Data were analyzed using Independent T-Test, Mann Whitney, and Chi-Square Test. Result: The results showed, there was a significant difference in the effectiveness of intravenous administration of ketorolac 30 mg and intravenous oxycodone 5 mg on pain as measured by cortisol levels in patients undergoing general anesthesia at dr. Mohammad Hoesin Palembang (p = 0.013). The value of cortisol levels in pre- operative patients who will be given general anesthesia at dr. There was no statistically significant difference between Mohammad Hoesin in the two groups (p = 0.107). The value of cortisol levels in preoperative patients who were given ketorolac 30 mg intravenously at dr. Mohammad Hoesin was 9.90 ± 4.2. The value of cortisol levels in postoperative patients who were given ketorolac 30 mg intravenously at dr. Mohammad Hoesin was 17.75 ± 6.08. The value of preoperative cortisol levels for patients who were given oxycodone 5 mg intravenously at dr. Mohammad Hoesin was 12.03 ± 5.10. The value of postoperative cortisol levels for patients who were given oxycodone 5 mg intravenously at dr. Mohammad Hoesin is 14.50 ± 4.75. Conclusion: There was a significant difference in the effectiveness of intravenous administration of ketorolac 30 mg and oxycodone 5 mg intravenously on BSS levels (p = 0.005) and VAS scores (p = 0.001) who underwent general anesthesia at dr. Mohammad Hoesin Palembang.

Association of subcutaneous or intravenous route of administration of casirivimab and imdevimab monoclonal antibodies with clinical outcomes in COVID-19.

Importance: Monoclonal antibody (mAb) treatment decreases hospitalization and death in outpatients with mild to moderate COVID 19; however, only intravenous administration has been evaluated in randomized clinical trials of treatment. Subcutaneous administration may expand outpatient treatment capacity and qualified staff available to administer treatment, but association with patient outcomes is understudied. Objective: To evaluate whether or not, i.) subcutaneous casirivimab and imdevimab treatment is associated with reduced 28 days hospitalization/death than non-treatment among mAb-eligible patients, and ii.) subcutaneous casirivimab and imdevimab treatment is clinically and statistically similar to intravenous casirivimab and imdevimab treatment. Design, Setting, and Participants: Prospective cohort study of outpatients in a learning health system in the United States with mild to moderate COVID 19 symptoms from July 14 to October 26, 2021 who were eligible for mAb treatment under emergency use authorization. A nontreated control group of eligible patients was also selected. Intervention: Subcutaneous injection or intravenous administration of the combined single dose of casirivimab 600mg and imdevimab 600mg. Main Outcomes and Measures: The primary outcome was the 28 day adjusted risk ratio or adjusted risk difference for hospitalization or death. Secondary outcomes included 28 day adjusted risk ratios/differences of hospitalization, death, composite endpoint of ED admission and hospitalization, and rates of adverse events. Results: Among 1,956 matched adults with mild to moderate COVID 19, patients who received casirivimab and imdevimab subcutaneously had a 28-day rate of hospitalization/death of 3.4% (n=652) compared to 7.8% (n=1,304) in nontreated controls [risk ratio 0.44 (95% confidence interval: 0.28 to 0.68, p < .001)]. Among 2,185 patients treated with subcutaneous (n=969) or intravenous (n=1,216) casirivimab and imdevimab, the 28 day rate of hospitalization/death was 2.8% vs. 1.7%, respectively which resulted in an adjusted risk difference of 1.5% (95% confidence interval: -0.5% to 3.5%, p=.14). The 28 day adjusted risk differences (subcutaneous and intravenous) for death, ICU admission, and mechanical ventilation were 0.3% or less, although the 95% confidence intervals were wide. Conclusions and Relevance: Subcutaneously administered casirivimab and imdevimab is associated with reduced risk adjusted hospitalization or death amongst outpatients with mild to moderate COVID 19 compared to no treatment and indicates low adjusted risk difference compared to patients treated intravenously.

SERUM CREATINE PHOSPHOKINASE ACTIVITY IN RABBIT DURING REGENERATION OF EXPERIMENTALLY DAMAGED MUSCLE TISSUE AND AFTER ITS STIMULATION BY TRANSPLANTED MSC

According to statistics, in modern veterinary practice, the percentage of muscle injuries among sport and working animals ranges from 40–70% of sports injuries. Quite often there are cases with muscle injuries of skeletal muscles, namely extremities. This scientific work describes the research methodology, stages of research step-by-step, and studies the relationship of dynamics of the activity of a single biochemical blood indicator. The essence of the method was to model the injury of muscle tissue performed by the skin and fascia dissection and cutting off in the area of midplane of the pelvic head of the biceps femoris muscle, measuring 1.5 x 1.5 cm to a depth of 1.5 cm of muscle tissue on 105 laboratory animals, divided into 4 groups with the use of various treatment methods. We analyze the results of one of the most effective biochemical methods for diagnosing muscle fiber of skeletal system damage and compare the activity of the enzyme creatine phosphokinase iso-enzyme depending on the stage of the study. Other research methods such as clinical, biochemical, ultrasonographic, histological research methods were recorded on 4, 7, 10, 14, 21, and 28 days. We analyzed the latest literature sources and concluded that on the 4th and 7th days, the level of creatine phosphokinase in the groups with intravenous administration, intramuscular administration of allogeneic mesenchymal stem cells is higher than the reference values but significantly lower compared to the control groups and the traditional method of treatment. But we observe a significant decrease in serum creatine phosphokinase levels in crawls on 10th day in the intravenous administration group compared to the control group of animals in 2 times, compared to traditional treatment in 1.6 times. The group of animals with intramuscular administration has reference values on the 14th day, compared with the control in 1.3 times lower, traditional treatment in 1.2 times. And on 21th day, we get reference values for a group of animals with traditional treatment. The level of creatine phosphokinase activity decreases in the control group of animals on 28th day of the research, which indicates a complete muscle rupture. The results of studies showed that the highest activity of the creatine phosphokinase enzyme during the study was shown by groups of animals with control and traditional treatment, which indicated significant structural, functional and destructive disorders of the muscle fibers of skeletal tissues with severe trauma. Thus, it is noted that the activity of the enzyme in conditions of damage of skeletal muscle tends to increase in accordance with the severity of the injury.