The aim: The purpose of this study was to assess the safety of propofol use during neurosurgical operations of different durations.
Materials andmethods: 72 patients weredividedintothreegroups depending on the type of operations; it were group 1 (ventriculostomy), group 2 (hematomaremoval), and group 3 (tumor removal), the anesthesia durations in these groups were65±5 min, 145±7 min and 225±10 min, respectively. Totalpropofoldoses in patientsofgroups 1, 2, and 3 were452±22 mg, 710±42 mg, and 966±51 mg, respectively. Before intervention and 1 h post operation, bloodgas composition, serum levels of transaminase, triglycerides, creatinephosphokinase, andpotassium, rateofurineoutput, levelof mean arterial pressure, and heart rhythm rate were determined.
Results: Nosignificantdeviations concerning hemodynamic indicators, bloodgas composition, changesof creatinekinaseactivity werefoundforanygrouppatientsduring the perioperativeperiod. The rate of urine output in all patients reached above 0.5 ml/kg/h without saluretics use.Thedeviatedtransaminasevalues returnedtotheir normal
onesduring 24 h post intervention. The triglycerides levels were in normal range proving the absence of propofol doses used on the lipid metabolism.
Conclusions: Anesthetic protection of neurosurgical interventions using propofol in doses 2.5-3 mg/kg and 3.60.3 mg/kg/h for induction anesthesia and for anesthesia support, respectively, is safe and does not lead to dangerous undesired consequences. However, the propofol use for prolonged patient sedation and his/her adaptation for prolonged lung ventilation needs further studies.
Long-term prophylaxis with a von Willebrand factor (VWF) concentrate is recommended in patients with von Willebrand disease (VWD) who have a history of severe and frequent bleeds. However, data from prospective studies are scarce. WIL-31, a prospective, noncontrolled, international phase 3 trial, investigated the efficacy and safety of Wilate prophylaxis in severe patients with VWD. Male and female patients 6 years or older with VWD types 1, 2 (except 2N), or 3 who had completed a prospective, 6-month, on-demand, run-in study (WIL-29) were eligible to receive Wilate prophylaxis for 12 months. At baseline, patients (n = 33) had a median age of 18 years. Six (18%) patients had severe type 1, 5 (15%) had type 2, and 22 (67%) had type 3 VWD. The primary end point of a >50% reduction in mean total annualized bleeding rate (TABR) with Wilate prophylaxis vs prior on-demand treatment was met; mean TABR during prophylaxis was 5.2, representing an 84.4% reduction. The bleeding reduction was consistent across age, sex, and VWD types. The mean spontaneous ABR was 3.2, representing an 86.9% reduction vs on-demand treatment. During prophylaxis, 10 (30.3%) patients had 0 bleeding events and 15 (45.5%) patients had 0 spontaneous bleeding events. Of 173 BEs, 84.4% were minor and 69.9% treated. No serious adverse events related to study treatment and no thrombotic events were recorded. Overall, WIL-31 showed that Wilate prophylaxis was efficacious and well-tolerated in pediatric and adult patients with VWD of all types. The WIL-29 and WIL-31 trials were registered at www.ClinicalTrials.gov as #NCT04053699 and #NCT04052698,
respectivelyvon Willebrand disease (VWD) is the most common inherited bleeding disorder with a prevalence of 0.6% to 1.3%.1 In VWD, hemostasis is impaired due to deficiency or dysfunction of von Willebrand factor (VWF).2 The severity of the bleeding phenotypes differs widely between patients with VWD, ranging from mild to severe, with type 3 VWD characterized by a severe bleeding phenotype.3 Long-term prophylaxis is recommended and well established in hemophilia. The goal of prophylaxis is to reduce bleeding rates to a minimum, reduce the risk of joint damage, and improve quality of
life.4 The positive experience with prophylaxis in hemophilia provides a rationale for prophylaxis in VWD.5,6 Indeed, in a post-hoc analysis of 331 patients with VWD, patients on VWF prophylaxis had fewer bleeds, fewer hospitalizations due to bleeds, and a lower likelihood for joint damage and moderate chronic pain, compared with patients who were eligible for but not receiving prophylaxis.7 Current guidelines recommend that patients with VWD who have a history of severe and frequent bleeds should use long-term prophylaxis with a VWF product.8 However, long-term prophylaxis is not the current standard of care for patients with VWD. In a survey of 6208 patients with VWD, only 1.6% received prophylaxis, most of them type 3 patients who had experienced joint bleeding.9 Wilate is a plasma-derived factor concentrate containing VWF and factor VIII (FVIII) in a physiological 1:1 activity ratio, which is indicated in patients with VWD for treatment of bleeds and perioperative management of bleeding and for prophylaxis.10,11 Across 4 clinical trials of patients with VWD, 19 patients received Wilate for prophylaxis, and their bleeding rates were reduced during prophylaxis compared with previous treatment.12 Here, we present the efficacy and safety results of the phase 3 WIL-31 study, which collected data specifically in patients with VWD undergoing regular prophylaxis with Wilate after a prospective 6-month run-in phase of on-demand treatment (WIL-29).
The cathodic electrochemical determination of molnupiravir on carbon nitride nanoparticles has been investigated for the first time. The electrochemical determination is given in neutral and mildly acidic media, and C3N4 plays the role of proton and electron transfer mediator. The analysis of the correspondent model confirms that the electrochemical determination of molnupiravir may be efficiently given with the easy interpretation of the analytical signal. As for the oscillatory behavior, its probability is more expressed than in the similar systems
UDC 637.344.8/577.153.2
Hydrolysate of whey protein concentrate (WPC) has been obtained under conditions that ensure retention of natural bioactive peptides. Prior to this, the WPC was characterised by electrophoresis, which revealed the presence of major whey proteins that can cause allergies and be precursors of bioactive peptides. The electrophoretic studies have allowed establishing that by the 120th minute, the proteolysis of the main protein allergens was almost complete. That is why this sample of WPC hydrolysate was used for further studies. Sephadex G-50 gel filtration has shown that 23.4% to 27.5% of proteolytic products soluble in trichloroacetic acid are lowmolecular-weight peptides with a molecular weight up to 1500 Da, while the control WPC sample contains less than 3 % of them. The hydrolysate obtained under physiological conditions was tested for allergenicity. The study was conducted in 18 rats divided into three groups. Animals of the first group (control) were given water, the second group whey protein concentrate, the third group pancreatin hydrolysate of whey proteins. According to the results of the experiment, the concentration of IgE in the 2 nd group is significantly higher compared with the control (49%), and in the 3rd group, does not differ from the control values. To detect possible sensitisation in the experimental animals, we used the specific leucocyte agglomeration reaction, the leucocyte specific lysis reaction, the values of the change in the concentration of circulating immune complexes, and the neutrophil damage index. The studies have shown that in the animals receiving WPC hydrolysate, no signs of an allergic reaction were detected, while the animals sensitised with WPC developed type I hypersensitivity (by the value of the IgE content).
Key words: whey proteins, allergenicity, proteolysis, bioactive peptides