TOLERANСЕ OF THE DRUG FOR VETERINARY USE TULATRIN

Mass antibacterial therapy carried out according to therapeutic and preventive schemes is considered to be a highly effective and the most rational measure for controlling infectious diseases in the conditions of large-scale industrial pig breeding. It was found that the long-term intramuscular use of the drug Tulatrin in a therapeutic and three-fold therapeutic dose does not have a pronounced pathological effect on pigs. During the experiment, no animal deaths and manifestations of clinical signs of intoxication (depression, vomiting, salivation, diarrhea, etc.) were noted. The animals were active and ate food well. The live weight of piglets in experimental groups does not significantly differ from the animals that were kept in the control groups. The liver is the most sensitive to the action of tulatromyc in with prolonged intake of the drug in higher doses, which is confirmed by the results of biochemical studies. However, the intrinsic hepatotoxicity associated with the use of high doses, or with prolonged use, is characteristic of all drugs of the macrolide group. It should be noted that in this case, the maximum increase in marker liver enzymes does not exceed 10 % of the upper limit of the norm, so we can say that the liver damage is of a trace nature, since the clinical significance is an increase in liver samples by at least 2 times. Also, the increase in total protein was not fatal and did not affect the change in the clinical status of animals. We did not note the death of animals and the manifestation of clinical signs of intoxication and hepatopathy. Tulatrin is one of the safe medicines, and is characterized by good tolerability. The results obtained confirm the safety of using the drug in the recommended dosage regimen.

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Opioids in COVID-19: Two Sides of a Coin

Frontiers in Pharmacology ◽

10.3389/fphar.2021.758637 ◽

2022 ◽

Vol 12 ◽

Author(s):

Camila Vantini Capasso Palamim ◽

Matheus Negri Boschiero ◽

Aléthea Guimarães Faria ◽

Felipe Eduardo Valencise ◽

Fernando Augusto Lima Marson

Keyword(s):

Adverse Effects ◽

Large Scale ◽

Ventilatory Support ◽

Orotracheal Intubation ◽

Opioid Use Disorder ◽

Opioid Use ◽

Risk Of Mortality ◽

High Doses ◽

Two Sides ◽

Higher Doses

Introduction: The treatment of most severe COVID-19 patients included the large-scale use of sedatives and analgesics–possibly in higher doses than usual–which was reported in the literature. The use of drugs that decrease mortality is necessary and opioids are important agents in procedures such as orotracheal intubation. However, these drugs seem to have been overestimated in the COVID-19 pandemic. We performed a review of the PubMed-Medline database to evaluate the use of opioids during this period. The following descriptors were used to enhance the search for papers: “Opioids”, “COVID-19,” “COVID-19 pandemic,” “SARS-CoV-2,” “Opioid use disorder,” “Opioid dependence” and the names of the drugs used. We also evaluated the distribution of COVID-19 patients in Brazil and the applicability of opioids in our country during the COVID-19 pandemic.Results: Several positive points were found in the use of opioids in the COVID-19 pandemic, for instance, they can be used for analgesia in orotracheal intubation, for chronic pain management, and as coadjutant in the management of acute intensification of pain. However, high doses of opioids might exacerbate the respiratory depression found in COVID-19 patients, their chronic use can trigger opioid tolerance and the higher doses used during the pandemic might result in greater adverse effects. Unfortunately, the pandemic also affected individuals with opioid use disorder, not only those individuals are at higher risk of mortality, hospitalization and need for ventilatory support, but measures taken to decrease the SARS-CoV-2 spread such as social isolation, might negatively affect the treatment for opioid use disorder. In Brazil, only morphine, remifentanil and fentanyl are available in the basic health care system for the treatment of COVID-19 patients. Out of the 5,273,598 opioid units used in this period all over the country, morphine, fentanyl, and remifentanil, accounted for, respectively, 559,270 (10.6%), 4,624,328 (87.6%), and 90,000 (1.8%) units. Many Brazilian regions with high number of confirmed cases of COVID-19 had few units of opioids available, as the Southeast region, with a 0.23 units of opioids per confirmed COVID-19 case, and the South region, with 0.05 units. In the COVID-19 pandemic scenario, positive points related to opioids were mainly the occurrence of analgesia, to facilitate intubation and their use as coadjutants in the management of acute intensification of pain, whereas the negative points were indiscriminate use, the presence of human immunosuppressor response and increased adverse effects due to higher doses of the drug.Conclusion: The importance of rational and individualized use of analgesic hypnotics and sedative anesthetics should be considered at all times, especially in situations of high demand such as the COVID-19 pandemic.

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THE IMPACT OF VETOM 20.76 BASED ON PREDATORY FUNGUS ARTHROBOTRYS OLIGOSPORA ON THE LEUCOCYTES IN THE GEESE BLOOD

Bulletin of NSAU (Novosibirsk State Agrarian University) ◽

10.31677/2072-6724-2019-53-4-103-108 ◽

2019 ◽

pp. 103-108

Author(s):

N. S. Iakovleva ◽

G. A. Nozdrin ◽

M. S. Iakovleva ◽

S. N. Tishkov ◽

A. I. Shevchenko

Keyword(s):

Live Weight ◽

Control Group ◽

Group 2 ◽

The Impact ◽

Higher Doses ◽

Leukocyte Concentration ◽

Experimental Group ◽

Different Doses ◽

Group 1

The paper demonstrates the results on the effect of new specimen Vetom 20.76 on concentration of leukocytes in the blood of geese on the basis of the predatory fungus Artusbotus oligospora. In order to achieve the goal of the experiment, one control group and six experimental groups were arranged on the principle of paired analogues. Each group contained 10 geese aged 1 month. The geese from the experimental groups received Vetom 20.76 in different doses in the morning with water once a day: the geese of the 1st experimental group - dose of 0.5 ppm/kg of live weight during 15 days; 2nd experimental group - 1 ppm/kg of live weight during 15 days; 3rd experimental group - 2 ppm/kg of live weight during 15 days, 4th experimental group - 0.5 ppm/kg live weight during 30 days, 5th experimental group - 1 ppm/kg live weight during 30 days and 6th - 2 ppm/kg live weight during 30 days. The geese of control group didn’t receive the specimen. The concentration of leukocytes in the blood of experimental geese increases in the period of specimen application as well as in the period of its aftereffect. If Vetom 20.76 is prescribed for 15 days, the effect of leukopoiesis stimulation finishes on the 30th day. If the specimen is applied during 30 days, the leukocytes in the blood continue to increase up to the 60th day. This long-term application of Vetom 20.76 dosed 0.5ppm/kg increases leucocytes within the physiological norm. Application of higher doses (1 and 2 ppm/kg) the leukocyte concentration conforms to the physiological norm

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Dose-dependent response to infection with Ebola virus in the ferret model and evidence of viral evolution in the eye.

Journal of Virology ◽

10.1128/jvi.00833-21 ◽

2021 ◽

Author(s):

Robert J. Watson ◽

Julia Tree ◽

Susan A. Fotheringham ◽

Yper Hall ◽

Xiaofeng Dong ◽

...

Keyword(s):

Large Scale ◽

Ebola Virus ◽

Virus Disease ◽

Viral Evolution ◽

Clinical Signs ◽

Disease Outbreaks ◽

The Body ◽

Medical Interventions ◽

Persistent Virus

Filoviruses are high consequence infections with limited approved medical countermeasures (MCMs). MCM development is dependent upon well-characterised animal models for the assessment of anti-viral agents and vaccines. Following large scale Ebola virus disease outbreaks in Africa, some survivors are left with long-term sequelae and persistent virus in immune-privileged sites for many years. We report the characterisation of the ferret as a model for Ebola virus (EBOV) infection, reproducing disease and lethality observed in humans. The onset of clinical signs is rapid, and EBOV is detected in the blood, oral and rectal swabs, and all tissues studied. We identify viral RNA in the eye (a site of immune privilege) and report on specific genomic changes in EBOV present in this structure. Thus, the ferret model has utility in testing MCMs that prevent or treat long term EBOV persistence in immune-privileged sites. Importance Recent re-emergence of Ebola in Guinea that caused over 28000 cases between 2013-2016 has been linked to the original virus from that region. It appears the virus has remained in the region for at least 5 years and is likely to have been maintained in humans. Persistence of Ebola in areas of the body for extended periods of time has been observed such as in the eye and semen. Despite the importance of re-introduction of Ebola from this route, such events are rare in the population which makes studying medical interventions to clear persistent virus difficult. We studied various doses of Ebola in ferrets and detected virus in the eyes of most ferrets. We believe this model will enable the study of medical interventions that promote clearance of Ebola virus from sites that promote persistence.

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Occipital cranioplasty using customized titanium prosthesis yields successful outcome in association with foramen magnum decompression in dogs suffering by Chiari-like malformation

American Journal of Veterinary Research ◽

10.2460/ajvr.21.11.0178 ◽

2021 ◽

pp. 1-8

Author(s):

Alessia S. Colverde ◽

Tommaso Nicetto ◽

Cristian Falzone

Keyword(s):

Clinical Status ◽

Clinical Signs ◽

Foramen Magnum ◽

Adjunctive Treatment ◽

Successful Outcome ◽

Foramen Magnum Decompression ◽

Mri Findings ◽

Cranial Fossa

Abstract OBJECTIVE To describe the use of a customized 3–D-printed titanium prosthesis as adjunctive treatment for foramen magnum decompression (FMD) in dogs with Chiari-like malformation (CM) and syringomyelia (SM). ANIMALS 8 dogs with clinical signs and MRI findings of CM-SM. PROCEDURES 3-D reconstruction of CT images of the head was used to simulate an occipital craniectomy and design the prosthesis. FMD was performed, and the prosthesis was implanted. Follow-up was performed 1, 6, and 12 months later, and clinical status was scored. Repeated MRI images were compared to identify changes involving the neural structures, particularly the syrinx. RESULTS All prostheses were easily positioned based on the preoperative 3-D models, with no complications. At 12 months after surgery, 3 dogs were free of previous medications, 4 were still receiving steroid medications but at lower doses, and 1 was occasionally receiving acupuncture. MRI of 5 dogs 6 to 20 months after surgery revealed resolution of SM (n = 1), reduced size of SM (3), or worse SM (1). All dogs showed an increase in size of the caudal cranial fossa. Dogs with a longer presurgical duration of the clinical signs and wider syrinx generally had worse outcomes than other dogs. CLINICAL RELEVANCE Findings suggested that use of customized 3–D-printed titanium prosthesis and associated FMD can represent an adjunctive option to medically treated dogs with CM-SM. Although the small number of cases precludes definitive conclusions, early surgical treatment, particularly in dogs with a small syrinx, could ensure better long-term outcomes, as previously suggested.

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Helixate®Nexgen in the Treatment of Patients with Hemophilia A: A Long-Term Pharmacovigilance Surveillance.

Blood ◽

10.1182/blood.v106.11.4091.4091 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4091-4091

Author(s):

Sabine Haertel ◽

Claudia Zacharias ◽

Hans-Herrmann Brackmann ◽

Zimmermann Roland ◽

Lenk Harald

Keyword(s):

Large Scale ◽

Hemophilia A ◽

Chinese Hamster ◽

Treatment Modalities ◽

Good Tolerability ◽

Safety Parameters ◽

Recombinant Fviii ◽

Set Up ◽

Observation Period

Abstract Comprehensive large-scale pharmacovigilance surveillances are very effective tools to collect data on products in the post authorization period. The evaluation presented here was set up to assess the long-term efficacy, safety and tolerability of the recombinant FVIII concentrate, Helixate®NexGen (in the US: Helixate®FS). Sixty-five hemophilia centers in Germany, Austria, Italy, France, and Sweden are participating in this ongoing international project. Previously untreated (PUP) and previously treated patients (PTP) at any age suffering from hemophilia A treated with Helixate®NexGen were eligible for the surveillance. Based on the standard schedule preferred at the centers, patients are routinely screened every 3 to 12 months. At these visits, the following parameters, as used routinely for these patients, were documented (non-interventional design): overall clinical response, pharmacokinetics, occurrence of bleedings, adverse drug reactions including the incidence of inhibitors, other laboratory safety parameters, coagulation parameters, relevant concomitant diseases, and medication. To determine the level of exposure, treatment modalities with Helixate®NexGen, including average factor consumption per month and exposure days are recorded. One hundred and ten patients have been included into the investigation up to now; data from 104 patients were available for this interim analysis including 2 PUPs. The median age was 25 years (range: 8 months – 68 years). One patient suffered from mild, eleven from moderate, and 89 from severe hemophilia A; in three patients the information on severity was missing. Most of the patients were treated prophylactically (92%, at least one infusion per week). Exposure to Helixate®NexGen during the pharmacovigilance ranged between 5 and 703 days. A total of 112 bleedings were documented during the observation period, with a range of 0 to 20 bleedings per patient per year. Efficacy of Helixate®NexGen was assessed as good or excellent in 97% of all cases. There were no cases of inhibitor development during the 2-year observation period, especially no cases of inhibitors when patients were switched from products produced in Chinese hamster ovary (CHO) cells to Helixate®NexGen, which is produced in baby hamster kidney (BHK) cells. The good tolerability of Helixate®NexGen was further supported by the fact that there were no other relevant side effects documented. In summary this pharmacovigilance supports the good tolerability and good/excellent efficacy data of Helixate®NexGen.

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Low hemoglobin at hemodialysis initiation: an international study of anemia management and mortality in the early dialysis period

Clinical Kidney Journal ◽

10.1093/ckj/sfz065 ◽

2019 ◽

Vol 13 (3) ◽

pp. 425-433

Author(s):

Angelo Karaboyas ◽

Hal Morgenstern ◽

Sandra Waechter ◽

Nancy L Fleischer ◽

Raymond Vanholder ◽

...

Keyword(s):

International Study ◽

First Year ◽

Advanced Chronic Kidney Disease ◽

Proactive Approach ◽

Anemia Management ◽

Iv Iron ◽

High Doses ◽

Dialysis Outcomes ◽

Higher Doses

Abstract Background Anemia at hemodialysis (HD) initiation is common. Correcting low hemoglobin (Hgb) before HD initiation may improve survival by avoiding potential harms of chronic anemia, high doses of erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron in the early HD period, and/or rapid Hgb rise. Methods We included 4604 incident HD patients from 21 countries in the Dialysis Outcomes and Practice Patterns Study Phases 4–5 (2009–15). Because low Hgb at HD start may reflect comorbidity or ESA hyporesponse, we restricted our analysis to the 80% of patients who achieved Hgb ≥10 g/dL 91–120 days after HD start (Month 4). Results About 53% of these patients had Hgb <10 g/dL in Month 1 (<30 days after HD start); they were younger with a similar comorbidity profile (versus Hgb ≥10 g/dL). Month 1 Hgb was associated with first-year HD mortality (adjusted hazard ratio for 1 g/dL higher Hgb was 0.89; 95% confidence interval: 0.81–0.97), despite minimal differences in Month 4 Hgb. Patients with lower Hgb in Month 1 received higher doses of ESA, but not IV iron, over the first 3 months of HD. Results were consistent when excluding catheter users or adjusting for IV iron and ESA dose over the first 3 months. Conclusions Even among patients with Hgb ≥10 g/dL 3 months later, anemia at HD initiation was common and associated with elevated mortality. A more proactive approach to anemia management in advanced chronic kidney disease (CKD) may thus improve survival on HD, though long-term prospective studies of non-dialysis CKD patients are needed.

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The use of the drug "Dextranal" to stimulate cellular immunity and prevention of gastrointestinal diseases calves

Veterinaria i kormlenie ◽

10.30917/att-vk-1814-9588-2021-2-9 ◽

2021 ◽

Author(s):

I.N. Penkova ◽

N.Y. Balybina ◽

V.Y. Koptev ◽

N.A. Shkill ◽

M.A. Leonova ◽

...

Keyword(s):

Cellular Immunity ◽

Clinical Signs ◽

Live Weight ◽

Gastrointestinal Diseases ◽

Phagocytic Index ◽

Control Group ◽

Maximum Increase ◽

Instructions For Use ◽

Experimental Group ◽

Newborn Animals

The article provides data on the preventive efficacy of the drug "Dextranal" in gastrointestinal diseases of calves and pigs, as well as the effect of the drug on the resistance of newborn animals. Calves and piglets of the experimental groups were injected with the drug from the first day of life, 5 injections at different intervals, depending on the group. During the experiment, the animals were clinically examined daily. When symptoms of gastrointestinal or respiratory tract lesions appeared, clinical signs and duration were recorded. All sick calves, regardless of the group, were prescribed the use of the antibiotic "Dorin-R" in a dosage according to the instructions for use. The shortest duration of the disease was noted in the calves of the first experimental group that received Dextranal at a dose of 0.06 mg / kg (3.0 ml) with an interval of 3 days. This prophylaxis scheme reduces the duration of the disease in animals by 15% compared to the control group. The analysis of the results of the opsonophagocytic reaction (OFR) indicates an increase in the parameters of the phagocytic index, phagocytic number and phagocytic activity of the blood of animals of the experimental groups, which indicates the direct effect of the drug on cellular immunity. The maximum increase in live weight is observed in calves of the first experimental group, exceeding the same indicator of control by 7.4%. When using the drug "Dextranal" to piglets at a dose of 0.02 mg / kg with an interval of 4 days, there is a decrease in animal mortality by 4%. Also, when using the drug according to this scheme, the piglets of the experimental group on the 14th and 42nd days have a maximum increase in live weight in comparison with the same indicator in the control group.

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Onset rate and intensity of signs of organophosphate poisoning related to paraoxon dose and survival in rats

SCRIPTA MEDICA ◽

10.5937/scriptamed52-31191 ◽

2021 ◽

Vol 52 (1) ◽

pp. 49-58

Author(s):

Žana Maksimović ◽

Dajana Duka ◽

Nataša Bednarčuk ◽

Ranko Škrbić ◽

Miloš Stojiljković

Keyword(s):

Lethal Dose ◽

Clinical Signs ◽

Synaptic Cleft ◽

Organophosphate Poisoning ◽

Time Intervals ◽

Stereotypic Behaviour ◽

High Doses ◽

Dose Dependent ◽

Higher Doses ◽

Onset Rate

Introduction: Oganophosphorus compounds (OP) bind to acetylcholinesterase (AChE) and inactivate it. In the synaptic cleft, undestroyed and accumulated acetylcholine produce the acute cholinergic effects. The aim of this study was to determine the frequency, speed of onset and intensity of certain signs of paraoxon poisoning depending on dose and outcome of poisoning. Methods: The study was conducted in adult Wistar rats. The median lethal dose (LD50) of paraoxon as well as protective ratio (PR) of atropine (10 mg/kg intramuscularly) was determined. Clinical signs of poisoning were observed: fasciculations, tremor, seizures, ataxia, piloerection, lacrimation, exophthalmos, bizzare/stereotypic behaviour and dyspnoea. The time from paraoxon injection to the first appearance of the sign of poisoning was recorded as well as the intensity of poisoning with evaluation at 10 time intervals throughout the 4 h observational period. Results: The LD50 of paraoxon was 0.33 mg/kg (subcutaneously) and PR of atropine was 2.73. Dose-dependent, piloerection occurred more often (p = 0.009) and at higher intensity (p = 0.016) at higher doses. Fasciculations, tremor, seizures and ataxia occurred significantly earlier at higher doses of paraoxon (p = 0.015, 0.002, 0.021 and 0.016, respectively), as well as the intensity of seizure, tremor and fasciculation. Piloerection (p = 0.002) and seizures occurred more frequently (p = 0.009) in non-survivors. Fasciculations, tremor, seizures and ataxia occurred significantly earlier and at higher intensity in non-survivors (p < 0.001, for all parameters), as well as dyspnoea (p = 0.009 and p = 0.048). In atropine-protected rats, nicotinic effects persevered, so they were the prognostic parameter of the severity of the poisoning. Conclusion: Seizures and fasciculations followed by tremor were strong prognostic parameters of the probability of lethal outcome of paraoxon poisoning. Also, the mentioned poisoning signs were with their intensity and speed of occurrence in a clear positive correlation with the administered dose of paraoxon. Even at high doses of paraoxon, atropine blocked the muscarinic (but not nicotinic) effects and somewhat mitigated the CNS toxic effects.

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Comparative Efficacy of Adalimumab and Etanercept in Children with Juvenile Idiopathic Arthritis Under 4 Years of Age Depending on Active Uveitis

The Open Rheumatology Journal ◽

10.2174/1874312901913010001 ◽

2019 ◽

Vol 13 (1) ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Ekaterina Alexeeva ◽

Tatyana Dvoryakovskaya ◽

Rina Denisova ◽

Tatyana Sleptsova ◽

Kseniya Isaeva ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Large Scale ◽

De Novo ◽

Clinical Signs ◽

Older Children ◽

Comparative Efficacy ◽

Drug Of Choice ◽

Laboratory Values

Introduction: In 2011, Etanercept (ETA) was approved for clinical application in patients with Juvenile Idiopathic Arthritis (JIA) older than 2 years of age; Adalimumab (ADA) was approved in 2013. However, the available data for these patients are not sufficient even in large-scale registers. In older children, uveitis is a factor taken into consideration when choosing anti-TNF therapy, so we believe that its onset at an early age may affect the efficacy of treatment with different anti-TNF drugs. Objectives: This study aimed to evaluate the comparative efficacy of ADA and ETA in children of young age depending on their uveitis status. Methods: Comparative analysis involved patients who had initiated ETA (n=49, no active uveitis) or ADA (n=25; 13 patients with active uveitis and 12 patients without uveitis) therapy at an age of ≤4 years. Treatment efficacy was evaluated according to the dynamics of clinical signs and laboratory values, the ACRPedi and Wallace criteria. Results: ETA and ADA proved very efficacious in children under 4 years of age already after the first month of therapy according to the disease activity scores, laboratory values, and morning stiffness duration. After 3 months of therapy, the number of affected joints was substantially reduced in all three groups (p<0.01). The percentage of patients who had achieved ACR50/70/90 by the end of the follow-up period was 42/41/38 (85.7/83.7/77.6%) in ETA group, 10/10/9 (76.9/76.9/69.2%) in ADA group with uveitis, and 9/7/5 (75/58.3/41.7) in ADA group without uveitis, respectively. A comparable proportion of ETA patients and ADA patients with uveitis achieved remission (26 (53.1%) and 7 (53.8%), respectively), while only 3 (25%) of ADA patients without uveitis achieved long-term clinical remission (p-values are insignificant). Conclusion: In children younger than 4 years, ADA shows higher efficacy in patients with uveitis as compared to those without uveitis. Children without uveitis show a better response to ETA, although there is a risk of de novo uveitis. Therefore, ADA is the drug of choice for children with uveitis under 4 years of age, while ETA is preferred in children without uveitis.

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Progestogen-Related Gross and Microscopic Changes in Female Beagles

Veterinary Pathology ◽

10.1177/030098587601300209 ◽

1976 ◽

Vol 13 (2) ◽

pp. 143-156 ◽

Cited By ~ 47

Author(s):

L. W. Nelson ◽

W. A. Kelly

Keyword(s):

Clinical Signs ◽

Follicular Development ◽

Mammary Development ◽

Megestrol Acetate ◽

High Dose ◽

Chlormadinone Acetate ◽

Human Dose ◽

Histologic Evaluation ◽

High Doses

Long-term studies of megestrol acetate and chlormadinone acetate in 100 female dogs are in progress. Doses of zero, one, 10 and 25 times the expected human dose of megestrol acetate and 25 times the expected human dose of chlormadinone acetate (on a milligram per kilogram body weight basis) are being given daily. During the first 4 years, eight dogs from each of the five groups were killed. The principal gross findings included enlarged uteri with mucoid material in the lumina, mammary development in dogs given middle and high doses of megestrol acetate and chlormadinone acetate, and thickened gallbladder walls in dogs given high doses of each. Histologic evaluation showed inhibition of ovulation for progestogen-treated dogs and suppression of ovarian follicular development with the high doses. Cystic endometrial hyperplasia was slight in the low-dose dogs and moderate to severe in most of the high-dose dogs; a few also had ulcerative endometritis and pyometra. The mammary glands of dogs given the middle and high doses produced lobules, acini, and secretion exceeding natural metestrus. Slight to marked cystic mucinous hyperplasia occurred in the gallbladders of most dogs given the high doses. Two high-dose megestrol dogs had clinical signs and microscopic pancreatic, renal, and ocular changes indicative of diabetes mellitus.

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