Resumption of meiotic maturation of oocytes, pre- and post-implantation mortality of embryos under ten-time intravenous treatment of silver nanoparticles in mice

Background: In recent years the use of silver nanoparticles (AgNP) has increased significantly being focused on assessing human health and environmental risks of nanotechnology.Methods: Research (two series) has been done on white laboratory mice. One dose (20 mg/kg) has been investigated. Frequency of treatment: one time per day for 10 times. Material for the study (ovaries, tubes and uterus) was taken under anesthetic anesthesia on the 10/11th, 21/22nd, 33/34th, 42/43rd days (after the last treatment). Oocyte meiotic maturation, pre- and post-implantation mortality of embryos under ten-time intravenous treatment of AgNP were investigation.Results: Under the ten-time treatment of AgNPs, the inhibition of reproductive function in female mice occurs: a decrease in the number and quality of ovarian oocytes; after male mice were planted, the females do not get pregnant to 21/22 day. The reproductive function in experimental animals is restored on the 40th day after the last treatment with AgNPs; there is no differences between the values of pre- and post-implantation mortality of embryos on the 33/34th day after male mice were planted; in one of the three experimental animals, 7 live pups were born on the 42/43rd day after the male was planted (in animals of the control group during this period: twice (6 ± 1 (n = 6) live pups).Conclusions: In mice females, under a ten-time treatment of AgNPs, the inhibition of reproductive function takes place; with the termination of the AgNPs treatment, the reproductive function is restored

Functional status of reproductive system under treatment of silver nanoparticles in female mice

Background: The use of silver nanoparticles (AgNP) has increased very significantly in recent years the work in science is currently on focused on assessing human health and environmental risks of nanotechnology. The aim of the present study was to estimate the functional status of the female reproductive system in mice under condition of the intravenous treatment of silver nanoparticles (AgNPs), namely to assess meiotic maturation of oocytes, viability of follicular cells surrounding the oocyte, spontaneous contractile activity of the myometrium and pre-and post-implantation mortality of embryos.Methods: Research (two series) has been done on white laboratory mice (8 weeks, 16-18 g). AgNPs are spherical nanoparticles of 30 nm (8 mg/ml for metal) diluted in water for injection. Method of treatment: intravenous. Two doses (2 mg/kg and 4 mg/kg) have been investigated. Frequency of treatment: one time per day with each dose of 1, 5 and 10 times (n=10 animals in each group). Material for the study (ovaries, uterus) were taken the day after the last AgNPs injection.Results: Ten-time AgNPs treatment (2 mg/kg and 4 mg/kg) results in inhibition of oocytes meiotic maturation in mice; a single- and five-time AgNPs treatment (2 mg/kg and 4 mg/kg) increases the number of apoptotic cells, while the ten-time AgNPs treatment results in an increase of the apoptotic and necrotic follicular cells surrounding oocytes; for the five-and ten-time AgNPs treatment (4 mg/kg) the index of contractility (IC) of the uterus increased; for the ten-time AgNPs treatment (2 mg/kg and 4 mg/kg) no differences in value of the embryonic mortality between control and study groups have been observed.Conclusions: This study suggests that the development of nanomaterials should be safer and non-toxic and the potential reprotoxicity of AgNPs should be investigated more carefully

Development of a national out-of-hospital transfusion protocol: a modified RAND Delphi study

Background: Early resuscitation with blood components or products is emerging as best practice in selected patients with trauma and medical patients; as a result, out-of-hospital transfusion (OHT) programs are being developed based on limited and often conflicting evidence. This study aimed to provide guidance to Canadian critical care transport organizations on the development of OHT protocols. Methods: The study period was July 2021 to June 2022. We used a modified RAND Delphi process to achieve consensus on statements created by the study team guiding various aspects of OHT in the context of critical care transport. Purposive sampling ensured representative distribution of participants in regard to geography and relevant clinical specialties. We conducted 2 written survey Delphi rounds, followed by a virtual panel discussion (round 3). Consensus was defined as a median score of at least 6 on a Likert scale ranging from 1 (“Definitely should not include”) to 7 (“Definitely should include”). Statements that did not achieve consensus in the first 2 rounds were discussed and voted on during the panel discussion. Results: Seventeen subject experts participated in the study, all of whom completed the 3 Delphi rounds. After the study process was completed, a total of 39 statements were agreed on, covering the following domains: general oversight and clinical governance, storage and transport of blood components and products, initiation of OHT, types of blood components and products, delivery and monitoring of OHT, indications for and use of hemostatic adjuncts, and resuscitation targets of OHT. Interpretation: This expert consensus document provides guidance on OHT best practices. The consensus statements should support efficient and safe OHT in national and international critical care transport programs. The transfusion of blood components such as red blood cells (RBCs) and plasma is increasingly common in prehospital and transport medicine.1–3 In addition, the potential benefits of out-of-hospital administration of whole blood or blood products such as fibrinogen and prothrombin complex concentrate in selected patients are being investigated. In this report, we use the umbrella term “out-of-hospital transfusion” (OHT) to refer to the transfusion of whole blood, blood components such as RBCs and plasma, or blood products such as fibrinogen and prothrombin complex concentrate. Although the increasing practice of OHT suggests general consensus on a likely clinical benefit, evidence regarding the effect of OHT on morbidity and mortality is limited and conflicting.2,4–6 The generalizability of the limited evidence is further complicated in that the feasibility and potential benefit of OHT are dependent on multiple regional factors such as geography, patient factors and health care configuration. For example, 2 secondary analyses of the data sets from the Prehospital Air Medical Plasma (PAMPer) and the Control of Major Bleeding After Trauma (COMBAT) clinical trials suggested that OHT was beneficial if transport times were greater than 20 minutes and that a benefit present in blunt trauma does not translate to a benefit in penetrating trauma.7,8 In addition, out-of-hospital management of acute hemorrhage extends beyond OHT and includes factors such as administration of tranexamic acid, avoidance of hypothermia and physical means of hemorrhage control where possible.9,10 Efficient and effective implementation of OHT requires a combination of medical and logistic considerations that span multiple specialties. This is particularly relevant in countries like Canada, with long transport times to tertiary care centres, and remote communities that have limited or no access to physicians or blood components and products at their local health care facilities.11 We invited an expert panel to provide expert opinions on out-of-hospital hemorrhage management and, in particular, OHT to develop national consensus recommendations to guide OHT practice and to begin to optimize the effectiveness and safety of OHT

Administration of an inhibitor of hydrogen sulfide (H₂S) synthesis via cystathionine γ-lyase (L-propargylglycine; PAG) increases esophageal injury/inflammation in hyperglycemic rats subjected to water-immersion stress.

<p>The exacerbation of histological damage by PAG (25 mg/kg) was reversed by co-administration of L-tryptophan (L-Trp). Both inhibitors of H₂S synthesis significantly reduced serum IL-10 and increased serum IL-17, and co-administration of L-Trp diminished these effects. The H₂S donor, NaHS, significantly increased IL-10 and reduced IL-17, and the combination of NaHS and L-Trp produced significantly greater changes in levels of these two cytokines. Bars represent the mean ± SEM of at least 6 rats/group. *p<0.05 versus the vehicle-treated group; ^ψp<0.05 versus the corresponding group not treated with L-Trp (one-way ANOVA and Neuman-Keuls test).</p

Administration of an inhibitor of hydrogen sulfide (H₂S) synthesis via cystathionine γ-lyase (L-propargylglycine; PAG) exacerbates esophageal injury/inflammation in hyperglycemic rats.

<p>Administration of PAG (25 mg/kg) resulted in a significant increase in the histological score of esophageal injury (panel A). PAG administration also reduced serum IL-10 and increased serum IL-17 levels. The effects of PAG on esophageal damage and serum IL-10 were reversed by co-adminstration of L-tryptophan (L-Trp). An inhibitor of another pathway of H₂S synthesis (CHH; O-carboxymethylhydroxylamine; 20 mg/kg) had no effect on esophageal injury, but produced similar changes to serum IL-10 and IL-17 levels as were seen in PAG-treated rats. Panel C shows the irregular hyperemia, stasis (arrows) and perivascular diapedesis that was observed in rats that on the fructose-supplemented drinking water that were treated with PAG. Panel D illustrates that this treatment also resulted in localized detachments of the epithelium from the basement membrane and destructive changes to the epithelial plate (arrow). X200 (hematoxylin and eosin staining). Bars represent the mean ± SEM of at least 6 rats/group. *p<0.05 versus the vehicle-treated group; ^ψp<0.05 versus the corresponding group not treated with L-tryptophan (one-way ANOVA and Neuman-Keuls test).</p

Summary of some of the key observations in models of mild, moderate and severe esophagitis in rats, and the effects of an inhibitors of hydrogen sulfide synthesis via cystathionine γ-lyase (L-propargylglycine; PAG).

<p>In healthy rats and in the rats with hyperglycemia- or hyperglycemia+stress-induced esophagitis, acute administration of PAG caused a significant exacerbation of esophageal inflammation. Serum levels of IL-10 decreased with the severity of esophagitis, and this was further enhanced in rats treated with PAG. In contrast, serum levels of IL-17 increased sharply in animal with esophagitis, in parallel with the severity of the disease, and administration of PAG caused further increases in all three models. *p<0.05 versus the corresponding vehicle-treated group (Student’s t-test).</p

Esophageal lesions with signs of nonerosive microscopic esophagitis induced by water-immersion stress after 28 days of consumption of fructose-supplemented drinking water.

<p>Panel A: Pretreatment with an inhibitor of cystathionine γ-lyase (L-propargylglycine; PAG) resulted in extensive esophageal inflammation, with profound submucosal leukocyte infiltration. Panel B: Macroscopic appearance of the lower esophagus of rat treated with PAG, with extensive perivascular hemorrhage. Panel C: Macroscopic appearance of lower esophagus of rat treated with PAG and L-tryptophan, the latter providing a protection against the detrimental effects of PAG.</p

Treatment of healthy rats with inhibitors of hydrogen sulfide (H₂S) synthesis produces negligible esophageal damage, but significantly alters serum levels of IL-10 and IL-17.

<p>Panel A: Small, but statistically significant changes in the histological score of lower esophageal integrity were observed following administration of either of the inhibitors of H₂S synthesis (PAG, L-propargylglycine and CHH, O-carboxymethylhydroxylamine). The changes induced by the H₂S inhibitors were limited to mild mucosa inflammation. Administration of the inhibitors of H₂S synthesis also resulted in significant decreases in serum IL-10 levels, while the H₂S donor, NaHS, had no effect. Small but significant increases in IL-17 levels were observed following administration of PAG, CHH and NaHS. Bars represent the mean ± SEM of at least 6 rats/group. *p<0.05 versus the vehicle-treated group (one-way ANOVA and Neuman-Keuls test).</p

Resumption of Meiotic Maturation of Oocytes, Pre- and Post-Implantational Embryonic Mortality under Conditions of Experimental Glomerulonephritis and Treatment of Silver Nanoparticles

The aim of the current study was to estimate the resumption of meiotic maturation of oocytes, pre- and post-implantation mortality of embryos under conditions of experimental glomerulonephritis and intravenous treatment of silver nanoparticles in mice. Experimental glomerulonephritis in mice was achieved by immunization of white laboratory mice of the first generation with a kidney antigen suspension derived from a parent. The treatment was carried out in the following way: Kidney antigen suspension - intraperitoneal three times 1 time per day; the procedure was repeated in 3 weeks, one time intraperitoneally with the same dose (10 mkL of suspension per 10 grams of body weight of the animal). Silver nanoparticles (AgNPs, 30 nm) - intravenous treatment three times: 1 time per day for 1 h before immunization of animals with suspension of kidney antigen; as well as in 3 weeks once with the same dose (2 mg/kg). Thus, the number of oocytes that resumed meiosis in vitro from animals under experimental glomerulonephritis decreased as compared to the numbers in control animals; no inhibition of meiotic resumption of oocytes of animals was established under conditions of AgNPs treatment; the AgNPs treatment under conditions of experimental glomerulonephritis increased the number of oocytes that resumed meiosis in vitro compared with such values in the control and under conditions of experimental glomerulonephritis. The value of post-implantation embryonic mortality increased under conditions of experimental glomerulonephritis; no infertility of implantation in females of mice under conditions of AgNPs treatment; the AgNPs treatment under conditions of experimental glomerulonephritis decreased post-implantation mortality of embryos