Biokemijski učinci ivermektina na spolne hormone i homeostazu minerala u krava baladi pasmine nakon teljenja.

This study investigated the effect of an antiparasitic ivermectin (IVM) drug on the endocrine reproductive hormones of twenty healthy adult 250-350 kg Baladi cows that were 4-7 years of age. The cows were divided into two groups (n = 10 each). The first was a control group injected with physiological saline; the second group was treated with the recommended therapeutic dose of IVM (0.2 mg/kg, s/c) one day after parturition. Blood samples were taken on the 1st, 15th, 30th and 90th day after IVM treatment. The results revealed that IVM injection at one day after parturition delayed estrous for up to 3 months (absence of estrous signs and rectal palpation revealed no ovarian structures). IVM significantly (P<0.05) decreased serum follicular stimulating hormone (FSH), luteinizing hormone (LH) and estradiol for up to 3 months. In addition, IVM significantly (P<0.05) increased serum progesterone, prolactin and cortisol for up to 3 months. Further, IVM caused unobservable changes in serum testosterone and sex hormones binding globulin. Serum calcium levels significantly increased on the 1st day of IVM injection, while serum phosphorus significantly decreased on the15th and 30th day of IVM injection. It was concluded that IVM delayed estrous in cows for three months via disturbances in the female reproductive hormones and calcium/phosphorus homeostasis. Therefore, it is recommended that IVM should not be injected directly after parturition. Furthermore, the increased calcium after IVM indicates that an overdose of IVM should not be counteracted by calcium therapy; instead, any other antiallergic preparation could be used.Kod 20 zdravih i odraslih krava baladi pasmine, čija se tjelesna masa kretala od 250 do 350 kg, a dob od 4 do 7 godina, istražen je učinak antiparazitika ivermektina (IVM) na spolne hormone. Krave su bile podijeljene u dvije skupine (10 u svakoj skupini). Prvoj, kontrolnoj skupini bila je prvog dana nakon teljenja ubrizgana fiziološka otopina soli natrijeva klorida, a drugoj preporučena terapijska doza ivermektina (0,2 mg/kg, s/c). Uzorci krvi bili su prikupljeni 1., 15., 30. i 90. dana nakon primjene ivermektina. Rezultati su pokazali da je njegova primjena dan nakon teljenja dovela do odgode estrusa u trajanju do 3 mjeseca (izostali znakovi estrusa i strukture pri rektalnoj palpaciji jajnika). U razdoblju od 3 mjeseca došlo je do signifikantnog (P<0,05) sniženja razine folikulostimulirajućeg hormona (FSH), luteinizirajućeg hormona (LH) i estradiola u serumu. U istom razdoblju ivermektin je uzrokovao signifikantan (P<0,05) porast serumskog progesterona, prolaktina i kortizola, te slabo uočljive promjene razine serumskog testosterona i globulina koji veže spolne hormone. Razina kalcija u serumu značajno je porasla 1. dana, dok je razina fosfora u serumu signifikantno pala 15. i 30. dana od primjene ivermektina. Zaključeno je da ivermektin odgađa estrus kod krava u trajanju od 3 mjeseca putem narušavanja ravnoteže spolnih hormona odnosno poremećaja homeostaze kalcija i fosfora. Zbog toga se ne preporučuje njegovo davanje netom nakon teljenja. Nadalje, povišena razina kalcija nakon njegove prekomjerne primjene ne bi se smjela suzbijati davanjem kalcija, već upotrebom drugih antialergijskih pripravaka

Physostigmine: A Plant Alkaloid Isolated from Physostigma venenosum: A Review on Pharmacokinetics, Pharmacological and Toxicological Activities

Medicinal plants have been documented as an important source for discovering new pharmaceutical molecules that have been used to treat serious diseases. Strikingly, previous reports stated that natural products and their derived compounds exhibit lesser side effects and improved efficacy than other synthetic counterparts. Physostigmine, a parasympathomimetic plant alkaloid isolated from the West African perennial shrub Physostigma venenosum, it shows a narrow therapeutic index and a short life span, despite its ability to penetrate the blood-brain barrier (BBB). It is a widely known reversible butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) inhibitor and has been documented to treat various ailments such as Alzheimer’s disease. Pharmacologically, physostigmine was first reported as an antidote for atropine scopolamine and belladonna alkaloids toxicity. Recently, it has been documented as a therapy for treating several ailments including glaucoma, myasthenia gravis and the intoxication caused by tricyclic antidepressant overdoses, anti-histamines, antipsychotics, and benzodiazepines. Physostigmine has been reported to be absorbed from the gastrointestinal tract and showed short half-life, as, after the oral administration of 2 mg of physostigmine salicylate, the peak plasma concentration reached to 30 minutes. This review examines the biological activities, pharmacokinetics, and toxicity of physostigmine extracted from P. venenosum. Keywords: Physostigma venenosum, Physostigmine, pharmacological activities, acetylcholinesterase and butyrylcholinesterase inhibitor

Pharmacokinetics and bioavailability of ceftiofur following intravenous and intramuscular administrations in broiler chickens

The study focussed on pharmacokinetics and bioavailability of ceftiofur (CFT) after receiving a single dose (2 mg/kg BW) through either intravenous (IV) or intramuscular (IM) injection. Eight broiler chickens, were used in a crossover design with a washout period of two weeks to analyze the behaviour of CFT. Ceftiofur concentrations in the plasma were determined by HPLC with UV detector. The pharmacokinetics of CFT was analyzed using non- compartmental analysis. Following IV injection, CFT elimination half-life (t1/2β) was 2.43 h, volume of distribution at steady state (Vdss) was 0.63 L/kg, and total body clearance (Cl) was 0.24 L/h/kg. Following a single intramuscular (IM) injection of CFT at the same dose, the drug was quickly absorbed into the bloodstream with an absorption half- life (t1/2ab) of 0.31 h. The maximum concentration of the drug in the plasma (Cmax) was 2.85 μg/mL and reached at a time (Tmax) of 0.57 h after injection and the bioavailability (F) of CFT was 96.25%. The results of the study revealed that CFT was absorbed rapidly and showed high bioavailability when administered by IM route. This suggests that CFT has a promising disposition in chickens, and its use could help determine the best dosage regimens for effective eradication of various infections in chickens

In vitro anticancer effects of a RAGE inhibitor discovered using a structure-based drug design system.

金沢大学医薬保健研究域医学系Receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor implicated in the pathogenesis of certain types of cancer. In the present study, papaverine was identified as a RAGE inhibitor using the conversion to small molecules through optimized‑peptide strategy drug design system. Papaverine significantly inhibited RAGE‑dependent nuclear factor κ‑B activation driven by high mobility group box‑1, a RAGE ligand. Using RAGE‑ or dominant‑negative RAGE‑expressing HT1080 human fibrosarcoma cells, the present study revealed that papaverine suppressed RAGE‑dependent cell proliferation and migration dose‑dependently. Furthermore, papaverine significantly inhibited cell invasion. The results of the present study suggested that papaverine could inhibit RAGE, and provided novel insights into the field of RAGE biology, particularly anticancer therapies.Embargo Period 6 month

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Dietary Supplementation of Phoenix dactylifera

The date palm (Phoenix dactylifera) seeds were utilized in some traditional medical remedies and have been investigated for their possible health benefits. This proposed study wanted to assess the effect of date palm seeds (DPS) dietary supplementation in comparison to mannan-oligosaccharides (Bio-Mos®) and β-glucan over antioxidant and immunity events that have effect on growth and carcass performances of broilers. An aggregate of 180, one-day-old, chicks were raised in the wire-floored cages and allotted into control, Bio-Mos (0.1%  Bio-Mos), β-glucan (0.1%  β-glucan), DPS2 (2% date crushed seeds), DPS4 (4% date crushed seeds), and DPS6 (6% date crushed seeds) groups. Broilers in DPS2 and DPS4 groups showed significant variations (P<0.05) in relative growth rate (RGR), feed conversion ratio (FCR), and efficiency of energy utilization in comparison to control group. Moreover, all DPS fed groups showed significant increases (P<0.05) in serum reduced glutathione (GSH) values. Meanwhile, both serum interferon-gamma (IFN-γ) and interleukin-2 (IL-2) levels were significantly increased (P<0.05) in DPS2. Consequently, obtained data revealed a substantial enhancement of performance, immunity, and antioxidant status by DPS supplementation in broiler that might be related to the antioxidant and immune-stimulant constituents of P. dactylifera seeds

The impact of recently published negative erythropoiesis-stimulating agent studies on the clinical management of cancer-related anemia at a single center

BACKGROUND AND OBJECTIVES: Anemia in cancer patients is common, but often under-recognized and under-treated. Erythropoiesis stimulating agents (ESAs) are widely used to prevent and treat cancer and chemotherapy-related anemia, but recent studies suggest a negative impact on disease progression and survival associated with their use. this retrospective study describes the prevalence of anemia in cancer patients and recent trends in its management given the negative studies. PATIENTS AND METHODS: All consecutive adult cancer patients (n=959) admitted to regular medical units over one year were reviewed. Patients with a hemoglobin (Hb) value <12 g/dL on admission were considered anemic. Information on the primary tumor, main reasons for admission and treatment given were collected. RESULTS: At the time of enrollment, anemia was detected in 755 (78.7%) patients. The mean hb value for anemic patients was 9.5 g/dL prevalence and severity of anemia varied according to tumor type and reason for admission. the majority (68.6%) of the anemic patients were not offered treatment. The mean Hb value at which treatment was started was 8.0 g/dL Anemia treatment was related to its severity; treatment rates were 94.4%, 32.9%, and 5.0% in patients with severe, moderate and mild anemia, respectively (P<.0001). blood transfusion was used the most while ESAS were rarely used. length of hospital stay was affected by the presence of anemia (7.2 days in anemic patients vs. 4.85 days in nonanemic patients) (P<.001). CONCLUSIONS: Blood transfusion was used the most for cancer-related anemia, while ESAs were rarely used. The majority of patients with moderate anemia were not treated, including patients on active chemotherapy. better guidelines addressing anemia management in this subgroup of patients are highly needed

Phytochemical Constituents, Folk Medicinal Uses, and Biological Activities of Genus Angelica: A Review

International audienceGenus Angelica is one of the widely distributed and well-known genera of family Umbelliferae. It is utilized mainly by Chinese and Korean populations especially in their folk medicine. Angelica comprises a lot of medicinally important phytoconstituents such as coumarins, furanocoumarins, flavonoids, essential oils, verbascosides, polysaccharides, etc. Members of this genus play important roles, namely antioxidant, anti-inflammatory, anti-microbial, anti-diabetic, skin-whitening, cytotoxic, hepatoprotective, and many others. This review draws attention to many species of genus Angelica with much focus on A. dahurica being one of the highly medicinally used species within this genus