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Introduction: Although numerous effective drugs are available on the market, the effects of the therapy are often missing. Possible reasons include problems with access to health care, lack of compliance or a tendency to self-medicate. Aim: The aim of the study was to analyze the structure of the drugs dispensed to patients in the pharmacy, as well as the knowledge and attitudes of patients towards the drugs they use. Material and Methods: Research has been conducted in 2 pharmacies-pharmacy "Galenpharm" and pharmacy "Janković" in Kula, during 10 working days, 3 hours each day at randomly selected terms during March 2023. The number and type of drugs dispensed were recorded, and the respondents were interviewed according to a questionnaire prepared in advance. Results: During the observed period, the largest number of drugs dispensed was from the group of drugs used for the treatment of disorders of the cardiovascular system. In 89% of cases, patients take medicines according to the doctor's recommendation. Patient's knowledge about the correct use of medications, dosing and taking them in relation to meals is satisfactory. The knowledge about side effects of drugs and possible interactions is minimal, although over 90% of respondents read the instructions for the drug from the original packaging of the drugs. Conclusion: Patient's knowledge about the drugs they take is limited. By not taking medications correctly, patients are undertreated, regardless of the correct diagnosis and well-chosen medications. Their knowledge about drugs is a stumbling block in successful pharmacotherapy.

Background/Aim: Acute myocardial infarction (AMI) is a consequence of complete coronary artery occlusion. There is a considerable seasonal variation in the incidence of AMI. The aim of the study was to establish a circadian and seasonal pattern of AMI. Methods: A retrospective observational study was conducted, using the database of the Institute of Emergency Medical Service of the City of Novi Sad. The study included 982 patients, both male and female, diagnosed with AMI (I.21 - ICD-10 code) in the period between 15 March 2018 and 14 March 2022. Data were classified according to the time of the day, days of the week, quarters and months. Data were analysed by using descriptive statistical methods, Mann-Whitney U test, Chi-squared test and Fisher's exact test. Results: AMI most frequently occurred between 6 am and 2 pm (389; 39.6 %). A statistically significant incidence of AMI was calculated for the periods between 6 am and 2 pm (ch2 = 39.69; p < 0.001) and between 2 pm and 10 pm (ch2 = 28.06; p < 0.001). Most cases of AMI were noted on Monday (153; 15.6 %) and in January (93; 9.5 %). The highest incidence of AMI was in the period between 15 March 2021 and 14 March 2022 (304; 31.0 %), while the lowest incidence was noted between 15 March 2019 and 14 March 2020 (190; 19.3 %). Conclusion: Circadian, seasonal and annual rhythm may have a significant impact on the incidence of AMI. This fact can have an important role in the prevention, timely recognition and adequate treatment of acute coronary disease.

The Republic of Serbia signed and ratified the Stockholm Convention on Persistent Organic Pollutants. Law on ratification of the Stockholm Convention was adopted and actions were defined through the National Implementation Plan and the Action Plan. On their basis Project Proper Management and Final Disposal of Polychlorinated Biphenyls (PCBs) was created. Institute Nikola Tesla (INT) participated in the realization of the project. In the period from 2015 to 2022, 601 tons of PCB oil was successfully decontaminated by the INT mobile plant, i.e. the PCB content was below 50 mg/kg, which classified the power transformers (PT) as non-contaminated [1,2]. If PT becomes waste or in case of necessary repair or oil regeneration, the required limit value is 10 mg/kg. According to data from INT database there are still 2637 PTs containing PCBs in the concentration range of 2 to 50 mg/kg. In this paper application of the environmentally closed INT decontamination technology for achieving low values of PCB in the oil is shown.

Background/Aim: Cardiac arrest (CA) is a leading cause of mortality in the last forty years worldwide. Immediately initiated cardiopulmonary resuscitation (CPR) improves chances for survival. Aim of this study was to determine the efficiency of the Emergency medical service (EMS) dispatch centre in the absence of the uniform emergency medical dispatch assessment protocols in the management of cardiac arrest. Methods: The retrospective and observational study was conducted in Institute for Emergency Medical Service Novi Sad (IEMS Novi Sad) Serbia during a one-year follow-up. The study included patients with out-of-hospital cardiac arrests who underwent CPR. Results: EMS teams of the IEMS Novi Sad had 198 CPRs in the follow-up period. In 142 (71.72 %) calls, the EMS dispatcher got information that the patient was unconscious. The reported reaction time I by the dispatchers for the unconscious patients was 1.37 ± 1.27 minutes, actual duration of the conversation between the dispatcher and a caller - was longer: 138.21 ± 103.02 seconds (p < 0.001). The average conversation time with a caller was 61.37 ± 31.13 seconds. In 6 (4.22 %) cases, the EMS team was dispatched to a patient before the phone call was terminated. At the moment of arrival, all patients were unconscious, 194 (94.37 %) were pulseless, while the remaining 8 (5.63 %) experienced cardiac arrest during the examination. The cardiac arrest was witnessed by a layman in 120 (84.51 %) cases and CPR was initiated by bystanders, before the arrival of the EMS team, only in 13 (10.83 %) patients. Twenty-seven (19.01 %) patients arrived in a hospital with vital signs. Conclusion: The absence of the uniform EMS dispatch assessment protocols for the triage of incoming calls and phone assisted CPR for lay rescuers decreases the survival rate of patients with cardiac arrest.

The need to increase the productivity and capacity of power transformers has conditioned the production of insulating papers of a higher thermal class. For this purpose, various techniques of solid insulation modification were applied, which enable the increase in thermal and chemical stability of the insulating paper during the operation of the transformer. The applied additives, primarily dicyandiamide (DICY) and polyacrylamide (PAM), are one form of cellulose modification in the final stages of paper production. A significant difference between the papers is the nitrogen content in the paper, which is characterized by the addition of amine compounds (additives). The paper presents the application of infrared spectroscopy with totally attenuated reflection (FTIR-ATR) in the characterization of paper samples. The aim is to observe the difference between regularly kraft and thermally upgraded paper reflected in the presence or absence of characteristic functional groups for additives. The strip identification at 2194-2154 cm-1 confirmed the presence of dicyandiamide additives (DICY) in the spectrum of the sample of thermally upgraded paper, which is different compared with the spectrum of regular kraft paper.

Background/Aim: Gliclazide is one of the most commonly prescribed oral anti-hyperglycaemic therapies in type 2 diabetes mellitus (T2D). Recently reported additional beneficial pharmacological properties of gliclazide, including immunomodulatory and anticoagulant activities, suggested its potential application in treatment of type 1 diabetes mellitus (T1D). However, following oral administration, gliclazide was shown to have poor and variable absorption directing research into development of novel pharmaceutical delivery systems of gliclazide suitable for T1D. Since bile acids have previously demonstrated stabilising and controlled-release effects on microcapsules, their use for preparation of microcapsules of gliclazide may lead to improvements in gliclazide release, absorption and antidiabetic effects. This investigation was aimed to evaluate drug absorption profiles and hypoglycaemic effects of alginate-based microcapsules of gliclazide, prepared together with or without cholic acid, in healthy rats. Methods: Thirty healthy Wistar rats with confirmed normal glucose blood concentration were allocated into five groups and administered with a single dose of either vehicle microcapsules, gliclazide in suspension, gliclazide microcapsules, gliclazide in suspension together with cholic acid or microencapsulated gliclazide in combination with cholic acid. Following respective gliclazide dose, blood was sampled over next 10 hours and blood glucose levels and gliclazide serum concentrations were measured. Results: This analysis demonstrated altered effects of different gliclazide formulations in healthy rats with the highest gliclazide absorption mirrored by the most profound hypoglycaemic effect being achieved after its oral administration as a suspension (p

The reliability of power transformers operation largely depends on the insulation system condition, especially on the condition of paper insulation. Determining the condition of paper insulation of transformers in use cannot be made by direct measurements. The most common way of assessing the paper insulation condition is by analyzing the content of 2-furfural dissolved in the insulating oil and by applying correlations between the degree of paper polymerization and the 2-furfural content in the insulating oil. The concentration of 2-furfural in the oil depends on the moisture content of the insulation system and the oxygen and acid content in the oil. In order to gain a better insight into the cumulative content of 2-furfural produced by paper degradation, excluding changes in the 2-furfural content caused by migration between paper and oil at different operating temperatures, dependence of the degree of polymerization of kraft paper to 2-FAL content in the oil, corrected to a reference temperature of 20°C, for a moisture content in cellulose of 1-1.5% and 3-4% is presented in this paper. This diagram has been verified on 4 transformers according to available data from the database of the Electrical Engineering Institute Nikola Tesla. In the future, this diagram should be completed for moisture content of 2.5% in cellulose insulation.

The exploitation of PCB contaminated power transformers and those which contain corrosive sulphur is related to the greatest risks to the environment, due to possible environmental accidents and faults and failures of transformers. The equipment contaminated with PCB require special attention, more frequent testing of transformer condition and control of oil leaking, while for corrosive oils standards and requirements defined in CIGRE TB 378, CIGRE TB 625, IEC 60296 and IEC 60422 are restrictive for the use of corrosive oils. Overview of the problems with PCB contaminated equipment and corrosive sulphur is provided in accordance to the latest knowledge in these areas. PCB decontamination, desulfurization and oil regeneration process is described by the application of patented technology developed in the 'Nikola Tesla' Institute. Summarized results of decontamination process of 310 PCB contaminated power transformers with different voltage levels and power and removal of corrosive sulphur from 29 transformers show the efficiency of this process for simultaneous removal of PCB, corrosive sulphur and oil ageing products.

Introduction. Cardiac arrest (CA) is defined as a sudden cessation of normal circulation of blood due to failure of the heart to contract effectively during systole. Objective. The aim of this study was to determine the difference in outcome among patients, depending on the location of out-of-hospital CA; to determine the influence of observed determinants on the survival rate. Methods. Observational and retrospective study was conducted in the Institute for Emergency Medical Service Novi Sad (IEMS NS). It included patients who underwent cardiopulmonary resuscitation (CPR) by medical ambulance squads. Patients were divided into three groups, based on the location of CA: private place, public place, and medical institution. Results. CA occurred in private places in 151 cases (76.26%). The shortest duration of a phone call with the dispatcher and Reaction Time I was in the group of patients with CA in a public place (59.1 ± 36.4 seconds and 137.1 ± 89.8 seconds, respectively). CA was recognized in more than 80% of cases, but CPR was initiated in only 9.09% of patients in private places and in 19.35% of patients in public places. Though they initially presented with shockable rhythm in 57.14% of cases in public places, this group has the worst immediate outcome (11.43%), in contrast to the patients with CA in medical institutions (58.33%). Factors determining the survival of patients with CA were CPR attempted immediately after collapse, initial rhythm and eyewitnesses of CA. Conclusion. In order to improve survival of patients with out-of-hospital CA, both education of laymen and introduction of standard questioning protocol in the IEMS Call Centre are necessary. [Projekat Ministarstva nauke Republike Srbije, br. 175007]

AIM: - condition assessment of the injured on the basis of the pre-hospital records vital parameters and injuries mechanism using GCS (Glasgow Coma Score), RTS (Revised Trauma Score), MGAP (Injury mechanism, GCS, patient years and systolic blood pressure) and GAP score (GCS, the patient years and systolic blood pressure) - final results assessment of severe trauma patients on the basis of the mentioned values score - measures impact of the prehospital care on the outcome at the traumatized patient MATERIALS AND METHODS: The retrospective research was conducted at the Emergency Medical Services Novi Sad (EMS).The study included patients wherein the physician set trauma diagnosis on the field than the Emergency Center (EC) of the Vojvodina Clinical Center confirmed that this is serious trauma. RESULTS: The study included 47 patients, statistically significant more man than women. The average age was 50,70±17,72 year. Statistically significant the biggest number of the injures happened in the traffic accidents. For an objective assessment of the injure severity are used two anatomical score AIS (Abberviated Injury Scale) and ISS score (Injury Severity Score). All patients had ISS score over 15 and this put them in the group of severely injured patients. Four scores determined prehospitaly based on vital parameters records, states of consciousness, injury severity and mode of injury(blunt or penetrating injuries). Within each score the minimal survival is in the serious injury group. Survived 36 patients(76,60%)to discharge from hospital. Mostly not survived patients with head injury. The average value of pre-hospital scores were lower than in the survival group. Prehospital scores smaller values were correlated with lower survival but MGAP score was the best indicator of severe trauma. Only its average value in the group of patients who not survive pointed to serious trauma. Venous line is placed at three quarters of the patients, fluid resuscitation was performed prehospitaly in two thirds patients and pain therapy applied in negligible number of patients. CONCLUSION: Patients with severe head and neck injuries fall into the highest-risk group of patients. Into the first 24 hours after injury within them mostly coming up to the death. In addition as the value of vital parameters prehospitaly lower it is the higher risk of death. Alone prehospital treatment has no effect on the outcome of injuries since it is not done in the large percentage of the injured patients.

Background/Objectives: With the increasing prevalence of Crohn's disease (CD), treatment options for patients who fail conventional and advanced therapy are highly needed. Therefore, we explored the safety and efficacy of extracorporeal photopheresis (ECP) using 5-aminolevulinic acid (ALA) and blue light (405 nm). Methods: Patients with active CD who failed or were intolerant to biological therapy were eligible. Mononuclear cells (90 mL) were collected from each patient using a Spectra Optia ® apheresis system and diluted with 100 mL of 0.9% sodium chloride in a collection bag. The cells were incubated with ALA at a concentration of 3 millimolar (mM) for 60 min ex vivo and illumination with an LED blue light (405 nm) source (BLUE-PIT ® ) before reinfusion to the patient. Recording of vital signs and adverse events were regularly performed. At week 13, we assessed the patients with colonoscopy, the Harvey Bradshaw Index (HBI), the Inflammatory Bowel disease Health Related Quality of Life Questionnaire, and the measurement of serum C-reactive protein and fecal calprotectin (FC) levels. Biopsies of the intestines were taken for immunohistochemistry. Results: Seven patients were included. Four patients completed the treatments, with a total of 24 treatments. Three of the four patients achieved a favorable response, including a lower HBI, lower FC levels, and/or endoscopic improvement. No significant adverse events were observed. The remaining three patients received only one, three, or five treatments due to technical difficulties, medical reasons, or the withdrawal of informed consent. Conclusions: ALA-based ECP appears safe and seems to give some clinical improvement for the patients with active CD who failed to respond to conventional and advanced therapies., Competing Interests: Photonamic GmbH & Co. (KG, Pinneberg, Germany) had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. The authors declare no conflicts of interest.

Background and Objectives : PoCUS ultrasound applications are widely used in everyday work, especially in the field of emergency medicine. The main goal of this research was to create a diagnostic and therapeutic protocol that will integrate ultrasound examination of the lungs, ultrasound measurements of the inferior vena cava (assessment of central venous pressure) and BREST scores (risk stratification for heart failure), with the aim of establishing a more effective differential diagnostic approach for dyspneic patients. Materials and Methods: A cross-sectional study was conducted in the emergency medicine department with the educational center of the community health center of Banja Luka. Eighty patients of both sexes were included and divided into experimental and control groups based on the presence or absence of dyspnea as a dominant subjective complaint. Based on the abovementioned variables, the LUSBI protocol (lung ultrasound/BREST score/inferior vena cava) was created, including profiles to determine the nature of the origin of complaints. The biochemical marker of heart failure NT pro-BNP served as a laboratory confirmation of the cardiac origin of the complaints. Results : The distribution of NT pro BNP values in the experimental group showed statistically significant differences between individual profiles of the LUSBI protocol ( p < 0.001). Patients assigned to group B PLAPS 2 had significantly higher average values of NT pro-BNP (20159.00 ± 3114.02 pg/mL) compared to other LUSBI profiles. Patients from the experimental group who had a high risk of heart failure according to their BREST scores also had a significantly higher average maximum expiratory diameter compared to those without heart failure ( p = 0.004). A statistically significant difference ( p = 0.001) in LUSBI profiles was observed between the groups of patients divided according to CVP categories. Conclusion : The integration of the LUSBI protocol into the differential diagnosis of dyspnea has been shown to be very effective in confirming or excluding a cardiac cause of the disease in patients.

The aim of this study is to propose a test method for the determination of the quality of transformer paper insulation. For this purpose, the oil/cellulose insulation systems were exposed to various accelerated aging tests. The results of the aging experiments of normal Kraft and thermally upgraded papers, two different types of transformer oil (mineral and natural ester), and copper are shown. Aging was carried out in various experiments at 150 °C, 160 °C, 170 °C, and 180 °C with dry (initial values ≤ 0.5%) and moistened cellulose insulation (initial values 3-3.5%). Following insulating oil and paper, degradation markers were measured: the degree of polymerization, tensile strength, furan derivates, methanol/ethanol, acidity, interfacial tension, and dissipation factor. It was found that the aging of cellulose insulation in cycles was 1.5-1.6 times faster in comparison to continuous aging, due to the more pronounced effect of hydrolytic mechanism in cyclic aging owing to the produced and absorbed water. Furthermore, it was observed that the high initial water content in cellulose increases the aging rate two to three times more than in the dry experimental setup. The proposed aging test in cycles can be used to achieve faster aging and to compare the quality of different insulating papers.

Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) which is the precursor of the photosensitizer protoporphyrin IX (PpIX) is an available treatment for several diseases. ALA-PDT induces the apoptosis and necrosis of target lesions. We have recently reported the effects of ALA-PDT on cytokines and exosomes of human healthy peripheral blood mononuclear cells (PBMCs). This study has investigated the ALA-PDT-mediated effects on PBMC subsets from patients with active Crohn's disease (CD). No effects on lymphocyte survival after ALA-PDT were observed, although the survival of CD3 - /CD19 + B-cells seemed slightly reduced in some samples. Interestingly, ALA-PDT clearly killed monocytes. The subcellular levels of cytokines and exosomes associated with inflammation were widely downregulated, which is consistent with our previous findings in PBMCs from healthy human subjects. These results suggest that ALA-PDT may be a potential treatment candidate for CD and other immune-mediated diseases.

Photodynamic therapy (PDT) is a non-invasive therapeutic modality based on the interaction between a photosensitive molecule called photosensitizer (PS) and visible light irradiation in the presence of oxygen molecule. Protoporphyrin IX (PpIX), an efficient and widely used PS, is hampered in clinical PDT by its poor water-solubility and tendency to self-aggregate. These features are strongly related to the PS hydrophilic-lipophilic balance. In order to improve the chemical properties of PpIX, a series of amphiphilic PpIX derivatives endowed with PEG 550 headgroups and hydrogenated or fluorinated tails was synthetized. Hydrophilic-lipophilic balance (HLB) and log p -values were computed for all of the prepared compounds. Their photochemical properties (spectroscopic characterization, photobleaching, and singlet oxygen quantum yield) were also evaluated followed by the in vitro studies of their cellular uptake, subcellular localization, and photocytotoxicity on three tumor cell lines (4T1, scc-U8, and WiDr cell lines). The results confirm the therapeutic potency of these new PpIX derivatives. Indeed, while all of the derivatives were perfectly water soluble, some of them exhibited an improved photodynamic effect compared to the parent PpIX.

Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), a precursor to the potent photosensitizer, protoporphyrin IX (PpIX), is an established modality for several malignant and premalignant diseases. This treatment is based on the light-activated PpIX in targeted lesions. Although numerous studies have confirmed the necrosis and apoptosis involved in the mechanism of action of this modality, little information is available for the change of exosome levels after treatment. We report from the first study on the effects of ALA-PDT on cytokines and exosomes of human healthy peripheral blood mononuclear cells (PBMCs). The treatment reduced the cytokines and exosomes studied, although there was variation among individual PBMC samples. This reduction is consistent with PDT-mediated survivals of subsets of PBMCs. More specifically, the ALA-PDT treatment apparently decreased all pro-inflammatory cytokines included, suggesting that this treatment may provide a strong anti-inflammatory effect. In addition, the treatment has decreased the levels of different types of exosomes, the HLA-DRDPDQ exosome in particular, which plays an important role in the rejection of organ transplantation as well as autoimmune diseases. These results may suggest future therapeutic strategies of ALA-PDT.

Background: The presence of low back pain in nurses is becoming increasingly prominent and it has significant impact both on the individual as well as on the community., Objective: The aim of this study was to determine the prevalence of low back pain among practicing nurses., Methods: The research has been conducted in five health care institutions in the area of Vojvodina. Data were collected using the Nordic Musculoskeletal Questionnaire (NMQ)., Results: Five hundred and twelve nurses participated in this study. Most of the participants (93.95%) indicated that they experienced discomfort or pain in the lower back in the last 12 months. Due to low back pain, 61.95% of participants had reduced working abilities and 76.09% of participants have never taken time off from work., Conclusions: Due to low back pain nurses have a reduced working capacity, but they nevertheless rarely seek medical help or the change of the work place. The implementation of better ergonomic approach and adequate organization of work could reduce the occurrence of low back pain.

Background: Professional drivers are part of the active working population, so there is a need for continuous improvement of operating efficiency and safety in driving. Reaction time is a very important driver's trait., Objective: The aim of this study was to examine the effects of age and driving experience on reaction times of professional drivers., Methods: This study assesses part of driving efficiency of professional drivers by measuring simple reaction time and complex reaction time which are important to driving safety. Reaction times of 278 male professional drivers were tested using a hardware-software system for determining the speed of response to psychomotor simple and complex audio-visual stimuli., Results: Our results showed a positive correlation between ageing and slowing of reaction times. This suggests that the natural ageing process clearly slows down reaction times., Conclusions: The response times of professional drivers are more dependent on age than on driving experience.

Environmental pollution caused by pharmaceuticals and their transformation products (TPs) has become an increasingly important concern, due to the increased use of pharmaceutical formulations exposed to environmental change. Considerable concerns have been raised regarding potential toxic effects of the transformation products of pharmaceutical formulations on human health. Environmental risk assessments are mostly based on one active component, which causes different ecotoxicological effects, albeit the particular component is present in the environment as a part of a multicomponent mixture with different pharmaceuticals and excipients. The purpose of this review was to present the insight and new knowledge recently obtained by studies on the risk of pharmaceutical formulations, including all contained excipients, pharmaceuticals, and their transformation products exposed to the environment. Numerous studies have shown that the level of pharmaceuticals in the environment is below toxic concentration; however, long exposure to very low concentrations can still lead to harmful concentrations in biota. Accordingly, the findings of this study are expected to highlight the existing issues of the effect of pharmaceutical formulations to the environment, including TPs, and help to determine future research directions towards accumulating the data and improving ecological risk assessment.

mAbs have emerged as a promising strategy for the treatment of cancer. However, in several malignancies, no effective antitumor mAbs are yet available. Identifying therapeutic mAbs that recognize common tumor antigens could render the treatment widely applicable. Here, a human single-chain variable fragment (scFv) antibody library was sequentially affinity selected against a panel of human cancer cell lines and an antibody fragment (named MS5) that bound to solid and blood cancer cells was identified. The MS5 scFv was fused to the human IgG1 Fc domain to generate an antibody (MS5-Fc fusion) that induced antibody-dependent cellular cytotoxicity and phagocytosis of cancer cells by macrophages. In addition, the MS5-Fc antibody bound to primary leukemia cells and induced antibody-dependent cellular cytotoxicity. In the majority of analyzed cancer cells, the MS5-Fc antibody induced cell surface redistribution of the receptor complexes, but not internalization, thus maximizing the accessibility of the IgG1 Fc domain to immune effector cells. In vitro stability studies showed that the MS5-Fc antibody was stable after 6 d of incubation in human serum, retaining ∼60% of its initial intact form. After intravenous injections, the antibody localized into tumor tissues and inhibited the growth of 3 different human tumor xenografts (breast, lymphoma, and leukemia). These antitumor effects were associated with tumor infiltration by macrophages and NK cells. In the Ramos B-cell lymphoma xenograft model, the MS5-Fc antibody exhibited a comparable antitumor effect as rituximab, a chimeric anti-CD20 IgG1 mAb. These results indicate that human antibodies with pan-cancer abilities can be generated from phage display libraries, and that the engineered MS5-Fc antibody could be an attractive agent for further clinical investigation.-Sioud, M., Westby, P., Vasovic, V., Fløisand, Y., Peng, Q. Development of a new high-affinity human antibody with antitumor activity against solid and blood malignancies.

Introduction: Ranitidine is a hydrophilic weak base and an H 2 -receptor antagonist which is commonly used for gastroesophageal reflux, including during pregnancy. It has limited placental permeation and can be used as a pre-anesthetic antacid to prevent aspiration of acidic stomach contents. Recent studies suggest that diabetes and hypertension may influence placental permeation of hydrophilic drugs. Thus, this study aimed to investigate the influence of diabetes and hypertension on ranitidine's placental permeation in pregnant women., Methods: Forty one pregnant women all scheduled for elective cesarean section entered the study: healthy control (n = 15), with hypertension (n = 16) and with gestational diabetes (n = 10). All women received 50 mg of ranitidine intravenously. Three samples of maternal plasma (after ranitidine application, at delivery and after delivery), and two umbilical cord samples (arterial and venous blood) were collected and analyzed for ranitidine concentrations. Maternal pharmacokinetic parameter were calculated as well as feto:maternal and umbilical cord arterial to venous concentration ratios., Results: Ranitidine maternal and umbilical cord (arterial and venous) concentrations were similar in all three groups and there were no difference between feto:maternal ratios nor volume of distribution, clearance and half life between the groups., Discussion: Fetal concentrations are dependent on maternal concentrations in healthy and hypertensive women but not in diabetic women. Hypertension and diabetes did not affect fetal handling of ranitidine. Though hypertension and diabetes did not influence ranitidine placental permeation, it appears they altered time needed to achieve unity between maternal and fetal plasma., (Copyright © 2016. Published by Elsevier Ltd.)

Therapeutic strategies aiming at mobilizing immune effector cells to kill tumor cells independent of tumor mutational load and MHC expression status are expected to benefit cancer patients. Recently, we engineered various peptide-Fc fusion proteins for directing Fcg receptor-bearing immune cells toward tumor cells. Here, we investigated the immunostimulatory and anti-tumor effects of one of the engineered Fc fusion proteins (WN-Fc). In contrast to the Fc control, soluble WN-Fc-1 fusion protein activated innate immune cells (e.g. monocytes, macrophages, dendritic cells, NK cells), resulting in cytokine production and surface display of the lytic granule marker CD107a on NK cells. An engineered Fc-fusion variant carrying two peptide sequences (WN-Fc-2) also activated immune cells and bound to various cancer cell types with high affinity, including the murine 4T1 breast carcinoma cells. When injected into 4T1 tumor-bearing BALB/c mice, both peptide-Fc fusions accumulated in tumor tissues as compared to other organs such as the lungs. Moreover, treatment of 4T1 tumor-bearing BALB/c mice by means of two intravenous injections of the WN-Fc fusion proteins inhibited tumor growth with WN-Fc-2 being more effective than WN-Fc-1. Treatment resulted in tumor infiltration by T cells and NK cells. These new engineered WN-Fc fusion proteins may be a promising alternative to existing immunotherapies for cancer.

Given their safe use in humans and inherent adjuvanticity, Lactic Acid Bacteria may offer several advantages over other mucosal delivery strategies for cancer vaccines. The objective of this study is to evaluate the immune responses in mice after oral immunization with Lactobacillus (L) plantarum WCFS1 expressing a cell-wall anchored tumor antigen NY-ESO-1. And to investigate the immunostimulatory potency of this new candidate vaccine on human dendritic cells (DCs). L. plantarum displaying NY-ESO-1 induced NY-ESO-1 specific antibodies and T-cell responses in mice. By contrast, L. plantarum displaying conserved proteins such as heat shock protein-27 and galectin-1, did not induce immunity, suggesting that immune tolerance to self-proteins cannot be broken by oral administration of L. plantarum. With respect to immunomodulation, immature DCs incubated with wild type or L. plantarum-NY-ESO-1 upregulated the expression of co-stimulatory molecules and secreted a large amount of interleukin (IL)-12, TNF-α, but not IL-4. Moreover, they upregulated the expression of immunosuppressive factors such as IL-10 and indoleamine 2,3-dioxygenase. Although L. plantarum-matured DCs expressed inhibitory molecules, they stimulated allogeneic T cells in-vitro. Collectively, the data indicate that L. plantarum-NY-ESO-1 can evoke antigen-specific immunity upon oral administration and induce DC maturation, raising the potential of its use in cancer immunotherapies.