Prenatal administration of heparin-binding epidermal growth factor-like growth factor in an experimental model of necrotizing enterocolitis decreased both incidence and severity of the disease

BackgroundNecrotizing enterocolitis (NEC) is the leading gastrointestinal cause of death in premature infants and causes long-term disabilities. Previously, enteral heparin-binding epidermal growth factor-like growth factor (HB-EGF) administered after birth demonstrated decreased incidence and severity of NEC in a neonatal animal model of NEC. We investigated the potential prophylactic strategy of preventing NEC using prenatally administered HB-EGF.MethodsAn HB-EGF (800 µg/kg/dose) dose was injected into pregnant rats via tail vein or intraperitoneal route 2 hours prior to delivery. After cesarean section (C-section) at 21 days’ gestation, the rat pups were subjected to the NEC protocol by inducing stressors: hypoxia, hypothermia, hypertonic feeds, and orogastric gavage of lipopolysaccharide (2 mg/kg). Postnatally, pups were monitored for 96 hours and assessed for the development of clinical and postmortem histological NEC.ResultsThe experimental NEC incidence in untreated, stressed rat pups was 66%. Compared with untreated pups, the maternal administration of HB-EGF correlated with a significant NEC incidence and severity decrease in rat pups. The strongest decrease was seen when HB-EGF was administered via the intraperitoneal route 2 hours prior to C-section (66% vs 31%, *p<0.05). Prenatal HB-EGF administration significantly increased pups’ survival after NEC protocol exposure, with the greatest benefit observed in the group that received HB-EGF intraperitoneally 2 hours before delivery.ConclusionsPrenatal administration of HB-EGF decreases the incidence and severity of NEC, preserves gut barrier function and increases survival. This may represent a novel prophylactic clinical strategy for NEC offered to mothers at risk of delivering a premature infant.

Intravenous whole blood transfusion results in faster recovery of vascular integrity and increased survival in experimental cerebral malaria

Transfusion of 10 mg/kg of whole blood via intraperitoneal route to mice with late-stage experimental cerebral malaria (ECM) along with artemether has been shown to result in markedly increased survival (75%) compared to artemether alone (51%). Intraperitoneal route was used to overcome the restrictions imposed by injection of large volumes of viscous fluid in small and deranged blood vessels of mice with ECM. In the present study, a method of intravenous transfusion was implemented by injecting 200mL of whole blood through the right jugular vein in mice with late-stage ECM, together with artemether given intraperitoneally, leading to a remarkable increase in survival, from 54% to 90%. On the contrary, mice receiving artemether plus plasma transfusion showed a worse outcome, with only 18% survival. Compared to the intraperitoneal route, intravascular transfusion led to faster and more pronounced recoveries of hematocrit, platelet counts, angiopoietins levels (ANG-1, ANG-2 and ANG-2/ANG-1) and blood brain barrier integrity. These findings indicate that whole blood transfusion when given intravenously show more efficacy over intraperitoneal transfusion, reinforcing evidence for benefit as an adjuvant therapy for cerebral malaria.

VP021 A WAY TO TREAT SPIGELIAN HERNIA

Aim “Spigelian hernia is uncommon and accounts for only 0.12–2% of all abdominal hernias. It is mandatory to perform surgical correction and in recent years the laparoscopic approach is gaining ground. The authors pretend to demonstrate a video of an outpatient laparoscopic repair of Spigelian hernia.” Material and Methods “53-year-old woman with a left Spigelian hernia referred to laparoscopic repair via intraperitoneal approach.” Results “The patient was submitted to laparoscopic correction with a Ventralex® mesh. The surgery went without any complication and under 30 minutes. A few hours after the surgery, the patient was discharged. In the follow-up appointment, the patient had no complaints or evidence of recurrence.” Conclusions “Spigelian hernias are rare and have a mandatory surgical indication. Traditionally, open surgical repair is most commonly used. However, laparoscopic approach is becoming increasingly popular since it allows faster recovery, shorter hospital stay, and less pain, with no commitment to recurrence. Currently, there are no studies that demonstrate the superiority of a laparoscopic technique (intraperitoneal, TAPP or TEP). The intraperitoneal route is a simple, faster, and easily reproducible approach.”

ESTIMATION OF THE INFLUENCE OF DIFFERENT METHODS OF ADMINISTRATION OF METHYLETHYLPYRIDINOL HYDROCHLORIDE (EMOXIPIN) ON ELIMINATION OF THE PATHOLOGY OF THE MICROCIRCULATORY BREED IN TRAUMATIC LESIONS OF LIMB MUSCLES

In this article, the authors reflect the results of experimental studies devoted to the study of traumatic lesions of limb muscles in laboratory animals. The effect of different routes of administration (intraperitoneal and intramuscular paravulnary) of methylethylpyridinol hydrochloride (emoxypine) on the state of the microvasculature was evaluated. In the course of the experiment, it was found that intramuscular paravulnar administration of emoxipin makes it possible to more effectively eliminate the pathology of the microvasculature in comparison with the intraperitoneal route of administration. Also, as a result of the studies, it was noted that the MSB staining method is the most appropriate in terms of fibrin differentiation and assessment of the state of the microvasculature. The data obtained will make it possible to develop new approaches in the treatment of traumatic lesions of the limb muscles.

Type I and Type III Interferons Differ in Their Adjuvant Activities for Influenza Vaccines

ABSTRACT Type I and type III interferons (IFNs) can promote adaptive immune responses in mice and improve vaccine-induced resistance to viral infections. The adjuvant effect of type III IFN (IFN-λ) specifically boosts mucosal immunity by an indirect mechanism, involving IFN-λ-induced production of thymic stromal lymphopoietin (TSLP), a cytokine that activates immune cells. To date, it remained unclear whether the previously described adjuvant effect of type I IFN (IFN-α/β) would also depend on TSLP and whether type I IFN stimulates different antibody subtypes. Here, we show that after infection with a live attenuated influenza virus, mice lacking functional type I IFN receptors failed to produce normal amounts of virus-specific IgG2c and IgA antibodies. In contrast, mice lacking functional IFN-λ receptors contained normal levels of virus-specific IgG2c but had reduced IgG1 and IgA antibody levels. When applied together with protein antigen, IFN-α stimulated the production of antigen-specific IgA and IgG2c to a greater extent than IgG1, irrespective of whether the mice expressed functional TSLP receptors and irrespective of whether the vaccine was applied by the intranasal or the intraperitoneal route. Taken together, these results demonstrate that the adjuvant activities of type I and type III IFNs are mechanistically distinct. IMPORTANCE Interferons can shape antiviral immune responses, but it is not well understood how they influence vaccine efficacy. We find that type I IFN preferentially promotes the production of antigen-specific IgG2c and IgA antibodies after infection with a live attenuated influenza virus or after immunization with influenza subunit vaccines. In contrast, type III IFN specifically enhances influenza virus-specific IgG1 and IgA production. The adjuvant effect of type I IFN was not dependent on TSLP, which is essential for the adjuvant effect of type III IFN. Type I IFN boosted vaccine-induced antibody production after immunization by the intranasal or the intraperitoneal route, whereas type III IFN exhibited its adjuvant activity only when the vaccine was delivered by the mucosal route. Our findings demonstrate that type I and type III IFNs trigger distinct pathways to enhance the efficacy of vaccines. This knowledge might be used to design more efficient vaccines against infectious diseases.

Phase I/II study of oxaliplatin dose escalation via a laparoscopic approach using pressurized aerosol intraperitoneal chemotherapy (PIPOX trial) for nonresectable peritoneal metastases of digestive cancers (stomach, small bowel and colorectal): Rationale and design

BackgroundThe annual incidence of gastrointestinal carcinomas (stomach, small bowel, colon and rectum) is increasing in Western countries, reaching 50,000 new cases each year in France. Peritoneal carcinomatosis (PC) is diagnosed in 15% of these patients. Complete cytoreductive surgery (CCS) plus Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) is the only therapy that can offer patients with PC a chance for long-term survival with a 5 year overall survival (OS) rate of 30–60% versus 0–5% with systemic chemotherapy alone. However, CCS plus HIPEC still presents serious limitations and very few patients (10%) are candidates for these radical treatments. PC remains a palliative setting for 90% of patients with a median survival ranging from 15 to 25 months. Innovative surgical therapies such as Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) therefore need to be developed to improve the prognosis. Potential benefits were obtained after intraperitoneal nebulization of oxaliplatin in patients with advanced PC from colorectal cancer. Innovative surgical therapies such as pressurized intraperitoneal aerosol chemotherapy (PIPAC) have been proposed as palliative locoregional treatment with some promising results. The dose of oxaliplatin currently established by nebulization (PIPAC) is really low at 92 mg/m2. However, the peritoneum acts as a barrier limiting the systemic passage of intraperitoneal drug. Oxaliplatin used at higher doses during PIPAC procedures could be a safe option and allow better intratumoral penetration of chemotherapy.Method and designThe proposed study is a multicenter phase I/II trial of oxaliplatin dose escalation during PIPAC. The aim is to determine the maximum tolerated dose of pressurized oxaliplatin administered by the intraperitoneal route (PIPAC) during two consecutive procedures at a 4–6 week interval for patients with extended peritoneal carcinomatosis from the gastrointestinal tract. Dose started at 90 mg/m2 and escalation was in 50 mg/m2 steps up to a maximum of 300 mg/m2.DiscussionOxaliplatin is an effective drug in gastrointestinal cancer and high doses given by the intraperitoneal route during HIPEC are well tolerated. In this phase I trial, we hypothesized that high-dose oxaliplatin during PIPAC is feasible and safe. The repeated local administration of high doses of oxaliplatin could improve tumor response and prognosis.Trial registrationProspective study. ClinicalTrials.gov: NCT03294252. EudraCT: 2016-003666-49