The Multi-Component Causes of Late Neonatal Sepsis—Can We Regulate Them?

Elucidating the mechanisms of bacterial translocation is crucial for the prevention and treatment of neonatal sepsis. In the present study, we aimed to evaluate the potential of lactoferrin to inhibit the development of late-onset blood infection in neonates. Our investigation evaluates the role of key stress factors leading to the translocation of intestinal bacteria into the bloodstream and, consequently, the development of life-threatening sepsis. Three stress factors, namely weaning, intraperitoneal administration of Gram-positive cocci and oral intake of Gram-negative rods, were found to act synergistically. We developed a novel model of rat pups sepsis induced by bacterial translocation and observed the inhibition of this process by supplementation of various forms of lactoferrin: iron-depleted (apolactoferrin), iron-saturated (hololactoferrin) and manganese-saturated lactoferrin. Additionally, lactoferrin saturated with manganese significantly increases the Lactobacillus bacterial population, which contributes to the fortification of the intestinal barrier and inhibits the translocation phenomenon. The acquired knowledge can be used to limit the development of sepsis in newborns in hospital neonatal intensive care units.

The Impact of Background γ- Radiation on Erythrocyte Nuclear Pathology, The Serotonergic System, and Cytochrome P-450 in Hens (Gallus Gallus Domesticus) from Azerbaijan

High levels of background γ-radiation exist in the suburbs of Baku, Azerbaijan. We examined the impact of radiation on erythrocyte nuclear pathologies, levels of cytochrome P-450, and serotonin-modulating anticonsolidation protein (SMAP) in the tissues of the hens from three settlements with different levels of background radiation. Higher levels of radiation resulted in increased nuclear pathologies, upregulation of tissue SMAP levels, and downregulation of cytochrome P-450.We also carried out controlled dosage studies on Wistar male rats which showed significant upregulation of heat shock proteins with molecular mass 70 kDa (HSP70) in the bone marrow 3 and 5 h later of SMAP intraperitoneal administration. Administration of SMAP to rats 3 h prior to γ-radiation exposure (8 Gy) provided significant protection to somatic cell nuclei. We conclude that SMAP can provide protection from the genotoxic effects of γ-radiation through upregulation of HSP70 or the transformation of chromatin into a condensed, more protective conformational state.

The Activities of the Central Nervous System Following Ethyl Acetate Extract of Mucuna pruriens Seed Administration in Male BALB/c Mice

A number of reports showed the beneficial psychotropic effects of many of the Nigerian medicinal plants, but few scientific studies have been carried out as empirical evidence. This study investigated the possible neurobehavioural effects of ethyl acetate extract of Mucuna pruriens (MP) seed in male BALB/c mice. Male BALB/c mice (2½-3 months old) were grouped into 5 (n=6), treated with normal saline (0.1 mL), n-propanol extract of MP (200, 100, 50 mg/kg) or reference drug haloperidol (HP) or diazepam (DZP); thereafter, subjected to diverse behavioural models to evaluate the central nervous system (CNS) effects of the extract. A bolus of MP (200, 100, and 50 mg/kg) decreased the rectal temperature, exploratory activities (locomotion, rearing and grooming), anxiety-like responses (% open-arms time, open-arm entries, and the total number of enclosed arms times). Additionally, a one-shot of intraperitoneal administration of MP decimated the total score of apomorphine-induced stereotyped behaviours. Latency to hexobarbitone-induced sleep increased significantly in the 200 mg/kg MP, unchanged in the 100 mg/kg MP, and decreased in the 50 mg/kg MP treated groups. There was a marked decrease in the markers of convulsion (tonic flexion, extension, clonic convulsion, stupor, and recovery time) following MP treatment, especially the higher doses (200 mg/kg and 100 mg/kg). In conclusion, the CNS effects of systemic administration of MP seed are not unrelated to its hypothermic, hypnotic, anxiolytic, and anticonvulsant effects.

Investigation of changes in rat’s blood metabolomic profile, caused by lead exposure

Introduction. The prevalence of lead in the environment, due to human production and economic activities, and the xenobiotic nature of the element substantiate the relevance of studying the changes caused by the action of this metal. Materials and methods. A non-target metabolomic screening of the blood of rats exposed to intraperitoneal administration of lead acetate by HPLC-mass spectrometry was carried out. The expression of the selected masses was compared with those for the control group of animals. The masses that significantly changed the intensity compared to the control were subjected to fragmentation to obtain characteristic fragments. The annotation of metabolites was performed by searching in MS/MS databases and by comparison with in silico fragmentation spectra. The involvement of annotated metabolites in metabolic processes was established by literature analyzing. Results. Non-target metabolomic screening revealed 37 m/z values for the exposed group, significantly changing the intensity compared to the control. Annotation using fragmentation spectra and in silico fragmentation allows establishing the structure of eight metabolites, including an epoxy derivative of linolic acid, 15-hydroxyeicosatetraenoic acid, four oxo- and hydroxyacylcarnitine derivatives of long-chain fatty acids, one acylcarnitine derivatives of medium-chain fatty acids and one lysophosphoserine. Conclusion. Analyzing the literature, the known functions of the identified metabolites were established and attributed to the known metabolic processes. So, oxo- and hydroxyacylcarnitines are derivatives for intermediate products of β-oxidation fatty acids - it is increased concentration compared to the control indicates a violation of this process under the influence of oxidative stress caused by lead. Epoxy and 15-hydroxy derivatives of fatty acids (increased content relative to the control group) act as regulatory metabolites (vasodynamic activity), on the one hand, and markers of lead-induced hypoxia on the other hand. The increase of the concentration for the lysophosphatidylserine derivative indicates the intensification of apoptotic processes in the organism of the exposed group in contrast to the control.

The Effect of Intraperitoneal Administration of Dexamethasone on Abdominal Pain and Shoulder Pain after Selected Cholecystectomy by Laparoscopic Method

Introduction: Laparoscopic cholecystectomy is the standard treatment of cholecystitis. In comparison to open surgery, it has advantages such as a shorter recovery period and a shorter hospital stay. One of the side effects of this treatment is abdominal and shoulder pain after surgery. The purpose of this study was to see how intraperitoneal dexamethasone affects abdominal and shoulder pain following laparoscopic cholecystectomy. Methods and materials: This study included 70 patients aged 18-70 years who were candidate for laparoscopic elective cholecystectomy. Using a random number table, patients were separated into two equal groups. In the first group, after laparoscopy and before trocar removal, 20 cc of ringer serum containing 8 mg dexamethasone was sprayed in the diaphragm and peritoneal cavity, and in the second group, 20 cc ringer was sprayed. Visual analog scale (VAS) pain score was used to assess post operation pain. Results: From 6 o'clock on, there was a substantial difference in abdominal pain between the two groups, with the control group experiencing higher pain. From 12 o'clock onwards, there was a strong association between shoulder discomfort in the two groups, and patients in the control group experienced more pain. Furthermore, the control group received more opioids. Patients in the control group experienced higher nausea and vomiting starting 12 hours after surgery. Conclusion: After laparoscopic surgery, dexamethasone can relieve abdominal and shoulder discomfort, as well as nausea and vomiting, and it can also reduce the need for opioids. Dexamethasone appears to be effective in minimizing postoperative complications. Keywords: Postoperative Pain, Intraperitoneal, Dexamethasone, Laparoscopy

Intraperitoneal Administration of Forskolin Reverses Motor Symptoms and Loss of Midbrain Dopamine Neurons in PINK1 Knockout Rats

Background: sParkinson’s disease (PD) is a relentless, chronic neurodegenerative disease characterized by the progressive loss of substantia nigra (SN) neurons that leads to the onset of motor and non-motor symptoms. Standard of care for PD consists of replenishing the loss of dopamine through oral administration of Levodopa; however, this treatment is not disease-modifying and often induces intolerable side effects. While the etiology that contributes to PD is largely unknown, emerging evidence in animal models suggests that a significant reduction in neuroprotective Protein Kinase A (PKA) signaling in the SN contributes to PD pathogenesis, suggesting that restoring PKA signaling in the midbrain may be a new anti-PD therapeutic alternative. Objective: We surmised that pharmacological activation of PKA via intraperitoneal administration of Forskolin exerts anti-PD effects in symptomatic PTEN-induced kinase 1 knockout (PINK1-KO), a bone fide in vivo model of PD. Methods: By using a beam balance and a grip strength analyzer, we show that Forskolin reverses motor symptoms and loss of hindlimb strength with long-lasting therapeutic effects (> 5 weeks) following the last dose. Results: In comparison, intraperitoneal treatment with Levodopa temporarily (24 h) reduces motor symptoms but unable to restore hindlimb strength in PINK1-KO rats. By using immunohistochemistry and an XF24e BioAnalyzer, Forskolin treatment reverses SN neurons loss, elevates brain energy production and restores PKA activity in SN in symptomatic PINK1-KO rats. Conclusion: Overall, our collective in vivo data suggest that Forskolin is a promising disease-modifying therapeutic alternative for PD and is superior to Levodopa because confers long-lasting therapeutic effects.

Design and evaluation of pharmacological properties of a new 1,3,4-thiadiazolylamide derivative of 2-propylpentanoic acid

Introduction: The use of the pharmacophoric approach is a promising direction for modifying the chemical structure of 2-propylpentanoic (valproic) acid in order to obtain new drugs. Materials and methods: In the experiments on mice, acute toxicity, neurotoxicity, antiepileptic activity and analgesic effect of N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propylpentanamide (valprazolamide) were evaluated. LD50 was determined by probit analysis. Neurotoxicity was determined in a rotarod test and a bar test in mice. The effects of valprazolamide on the exploratory behavior of mice in open field test and in a light/dark transition test were evaluated. Its antiepileptic activity was tested in mice against seizures induced by maximal electroshock, pentylenetetrazole (scPTZ); isoniazid, thiosemicarbazide, pilocarpine, and camphor. The analgesic effect was studied in a hot plate test. Results and discussion: N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propylpentanamide was obtained by introducing pharmacophores into the structure of 2-propylpentanoic acid: a substituted amide group and an electron-donor domain of 1,3,4-thiadiazole. The LD50 value for intraperitoneal administration of a new 2-propylpentanoic acid: derivative to mice was 924.8 mg/kg, and the TD50 value in the rotarod test and the bar test were 456.7 mg/kg and 546.7 mg/kg, respectively. The suppression of orienting responses in the animals was noted when it was administered in neurotoxic doses. Valprazolamide showed the most antiepileptic activity on models of MES, scPTZ and isoniazid antagonism tests. The ED50 values were 138.4 mg/kg, 74.5 mg/kg, and 126.8 mg/kg, respectively. The therapeutic indices for these models of epilepsy were 6.7; 12.4; 7.3, and protective index – 3.3; 6.1 and 3.6, respectively. In the hot plate test, valprazolamide increased the latency period before a defensive response to a thermal stimulus (ED50 165 mg/kg). Conclusion: N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propylpentanamide is a new 1,3,4-thiadiazolylamide derivative of 2-propylpentanoic acid with antiepileptic and analgesic activities, which belongs to the group of low-toxic agents. Graphic abstract N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propylpentanamide (3D) LD50=924.8 mg/kg (mice, intraperitoneally) TD50=456.7 mg/kg (rotarod, mice, intraperitoneally) ED50=138.4 mg/kg (MES, mice, intraperitoneally) ED50=74.5 mg/kg (scPTZ, mice, intraperitoneally)