Deoxycholic Acid as a Modifier of the Permeation of Gliclazide through the Blood Brain Barrier of a Rat

Major problem for diabetic patients represents damage of blood vessels and the oxidative stress of the brain cells due to increased concentration of free radicals and poor nutrition of brain cells. Gliclazide has antioxidative properties and poor blood brain barrier (BBB) penetration. Bile acids are known for their hypoglycemic effect and as promoters of drug penetration across biological membranes. Accordingly, the aim of this study is to investigate whether the bile acid (deoxycholic acid) can change the permeation of gliclazide, through the blood brain barrier of a rat model type-1 diabetes. Twenty-four male Wistar rats were randomly allocated to four groups, of which, two were given alloxan intraperitoneally (100 mg/kg) to induce diabetes. One diabetic group and one healthy group were given a bolus gliclazide intra-arterially (20 mg/kg), while the other two groups apart from gliclazide got deoxycholic acid (4 mg/kg) subcutaneously. Blood samples were collected 30, 60, 150, and 240 seconds after dose, brain tissues were immediately excised and blood glucose and gliclazide concentrations were measured. Penetration of gliclazide in groups without deoxycholic acid pretreatment was increased in diabetic animals compared to healthy animals. Also in both, the healthy and diabetic animals, deoxycholic acid increased the permeation of gliclazide through that in BBB

A review of the international early recommendations for departments organization and cancer management priorities during the global COVID-19 pandemic: applicability in low- and middle-income countries.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a new virus that has never been identified in humans before. COVID-19 caused at the time of writing of this article, 2.5 million cases of infections in 193 countries with 165,000 deaths, including two-third in Europe. In this context, Oncology Departments of the affected countries had to adapt quickly their health system care and establish new organizations and priorities. Thus, numerous recommendations and therapeutic options have been reported to optimize therapy delivery to patients with chronic disease and cancer. Obviously, while these cancer care recommendations are immediately applicable in Europe, they may not be applicable in certain emerging and low- and middle-income countries (LMICs). In this review, we aimed to summarize these international guidelines in accordance with cancer types, making a synthesis for daily practice to protect patients, staff and tailor anti-cancer therapy delivery taking into account patients/tumour criteria and tools availability. Thus, we will discuss their applicability in the LMICs with different organizations, limited means and different constraints

A Crucial Role for Infected-Cell/Antibody Immune Complexes in the Enhancement of Endogenous Antiviral Immunity by Short Passive Immunotherapy

Antiviral monoclonal antibodies (mAbs) represent promising therapeutics. However, most mAbs-based immunotherapies conducted so far have only considered the blunting of viral propagation and not other possible therapeutic effects independent of virus neutralization, namely the modulation of the endogenous immune response. As induction of long-term antiviral immunity still remains a paramount challenge for treating chronic infections, we have asked here whether neutralizing mAbs can, in addition to blunting viral propagation, exert immunomodulatory effects with protective outcomes. Supporting this idea, we report here that mice infected with the FrCasE murine retrovirus on day 8 after birth die of leukemia within 4–5 months and mount a non-protective immune response, whereas those rapidly subjected to short immunotherapy with a neutralizing mAb survive healthy and mount a long-lasting protective antiviral immunity with strong humoral and cellular immune responses. Interestingly, the administered mAb mediates lysis of infected cells through an antibody-dependent cell cytotoxicity (ADCC) mechanism. In addition, it forms immune complexes (ICs) with infected cells that enhance antiviral CTL responses through FcγR-mediated binding to dendritic cells (DCs). Importantly, the endogenous antiviral antibodies generated in mAb-treated mice also display the same properties, allowing containment of viral propagation and enhancement of memory cellular responses after disappearance of the administered mAb. Thus, our data demonstrate that neutralizing antiviral mAbs can act as immunomodulatory agents capable of stimulating a protective immunity lasting long after the end of the treatment. They also show an important role of infected-cells/antibody complexes in the induction and the maintenance of protective immunity through enhancement of both primary and memory antiviral T-cell responses. They also indicate that targeting infected cells, and not just viruses, by antibodies can be crucial for elicitation of efficient, long-lasting antiviral T-cell responses. This must be considered when designing antiviral mAb-based immunotherapies

Efficacy of fentanyl transdermal patch in pain control after lower third molar surgery: A preliminary study

© Medicina Oral S. L. Background: Surgical removal of impacted lower third molars is a common oral surgical procedure, generally followed by moderate to severe postoperative pain. Transdermal drug delivery as a concept offers interesting possibilities for postoperative pain control. The aim of this study was to evaluate the efficacy of transdermal system with fentanyl in relieving pain following impacted lower third molar surgery. Material and Methods: Seventeen patients with bilateral impacted lower third molars were included in this preliminary study. For postoperative pain control, patients randomly received a fentanyl patch plus placebo tablet after the first operation and regular (placebo) patch and an analgesic, after the second operation. Analgesia was evaluated during first 24 hours postoperatively according to patients’ reports about time of first pain appearance and additional analgesic consumption. Pain severity was rated using a 10 cm long visual analogue scale (VAS). Results: Intensity of postoperative pain and postoperative analgesic consumption were significantly lower after the Fentanyl Transdermal System (FTS) was applied (p<0.05). Duration of postoperative analgesia was significantly higher with FTS when compared to control treatment (p<0.05). Conclusions: Based on the results of this preliminary study, transdermal system with fentanyl significantly reduced postoperative pain after third molar surgery

Oral rehabilitation of a patient with systemic lupus erythematosus using implant-supported fixed dentures – A case report with review of important considerations

© 2018, Serbia Medical Society. All rights reserved. Introduction Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease with a variety of oral manifestations (dry mouth, reduced salivary flow, painful mucosal lesions and restricted mouth opening, impaired oral hygiene maintenance), as well as possible far-reaching systemic implications. In the context of SLE, oral rehabilitation with dental implants might be the most appropriate solution. However, a lack of available literature, as well as the absence of treatment protocols, often leads to unsatisfactory management of these patients. The aim of this paper was to describe oral rehabilitation of a patient with SLE using dental implants and fixed dentures in both jaws. Case outline A 66-year-old female patient, who had suffered from SLE for over 30 years, was referred for oral rehabilitation as her chief complaints related to the existing mobile partial dentures in the jaws and poor chewing ability. Proposed oral rehabilitation with fixed dentures supported by six dental implants in the maxilla and four dental implants in the mandible, as well as prosthetic restoration of the mandibular teeth, was accepted by the patient. During the follow-up period of three years, no biological complications were observed related to the performed treatment. Conclusion Dental implants might be the most suitable treatment modality for oral rehabilitation of patients suffering from SLE

SOME ASPECTS OF MINIMUM WEIGHT DESIGN OF AIRCRAFT STRUCTURAL COMPONENTS

SOME ASPECTS OF MINIMUM WEIGHT DESIGN OF AIRCRAFT STRUCTURAL COMPONENTS; „International Conference of Experimental and Numerical Investigations and New Technologie

DETERMINATION OF FRACTURE MECHANICS PARAMETERS OF STRUCTURAL COMPONENTS UNDER THERMOMECHANICAL LOADS

Rotational components of aero engine turbine are the most important components. It operates at high temperature and under conditions of extreme environmental attack such as oxidation, corrosion and wear. These conditions can cause cracking of rotational components. The failure damage modes of turbine are classified in terms of main components as flow path parts, rotating such as rotor, groove, disk, and blade. Aero-engine turbine components such as discs and blades are susceptible to environmentally assisted cracking. Unlike fatigue crack growth, this involves crack growth under constant load. If the crack grows long enough, sudden failure can occur with catastrophic consequences. It is therefore desirable to identify the limiting crack size within fixings so that they can be inspected at regular intervals and removed from service before failure occurs. Three dimensional axis-symmetric finite element models were created to simulate a disc and the portion of a blade. The finite element method (FEM) allowed the prediction of the point of crack initiation and the crack propagation using the orientations of the maximum principal stresses. Stress intensity factor (SIF) is the base parameter in strength analysis regarding fracture mechanics. For a correct determination of SIF in this paper, combining J-integral approach and FEM is used. J-integral is a path independent integral around the crack tip

Effect of Simultaneous Exposure to Benzene and Ethanol on Urinary Thioether Excretion

The toxicity of benzene is not an issue of the past, especially in developing countries. Bone marrow toxicity is demonstrated among workers. In this study, the effect of simultaneous exposure to benzene and ethanol on benzene metabolism in mice was investigated by measuring the excretion of thioethers in urine. Urinary thioether excretion significantly decreased in the mice receiving both benzene and ethanol compared with the animals receiving benzene only. The assay of determining thioethers in urine samples in this study is a simple and low-cost method, thus suitable for routine use, especially in developing countries, not only for benzene,but also for other alkilating agents, which can be found during occupational exposure. Our results suggest that further research is needed to elucidate the mechanisms of decreased urinary excretion of thioether after simultaneous exposure to benzene and ethanol

Correlation between in vitro tests for blood brain barrier penetration with in vivo gliclazide penetration

Aim: The aim of this study was to investigate whether in vitro models of gliclazide distribution in systems n-octanol/water and cyclohexane/water are good in vitro models for the prediction of its penetration as well as for the prediction of influence of dexycholic acid (DCA) influence on penetration. Patients (or Materials) and Methods: Distribution coefficient (logD) was determined using a …Flask shake “method. Partition profile was determined over physiological pH range (from pH 1.2 HCl solution, pH 4.5 acetate buffer, pH 6.8 and 7.4 phosphate buffer, and pH 7 distilled water) for 5 combinations of n-octanol or cyclohexane with aquase gliclazide solution (10 µg/mL) of different pH and with or without the addition of DCA (0.5 mM) into n-octanol or cyclohexane phase. The analyses were done in triplicate for each pair of organic solvent/ water. Concentrations of gliclazide were determined using high-performance liquid chromatography. Values of logD at pH 7.4 were compared with literature date of gliclazide BBB penetration and influence of DCA on it penetration.Results: Higher partition into organic layer was found in system n-octanol/water than cyclohexane/water. Also DCA increased partition of gliclazide in system cyclohexane/water but not in system n-octanol/water. Value of logD at pH 7.4 without DCA in organic layer in system n-octanol/water was 0.34 (0.05) and in system cyclohexane/water was –0.74 (0.11). Value of logD at pH 7.4 with DCA in organic layer in system n-octanol/water was 0.54 (0.07) and in system cyclohexane/water was 0.18 (0.01). Thus, partition of gliclazide in system cyclohexane/water better correlate with in vivo data where penetration of gliclazide was increased with DCA pretreatement, but in diabetic animals, penetration was increased in group with and without DCA pretreatment what this in vitro system could not predict. Conclusion: Investigated system cyclohexane/water predicted poor gliclazide BBB penetration and the influence of DA on gliclazide penetration but system n-octanol/water failed to do so. However, more substances are need to claim that system cyclohexane/water successfully could predict drugs BBB penetration