Hospital Acquired MRSA Penumonia

Background: Antibiotic resistance is a growing problem and particularly of concern in nosocomial infections. Nosocomial pneumonia occurs in 0.4—1.1% of hospitalized patients. It is the most common infection in intensive care units. Bacterial colonization of the upper airway followed by micro aspiration or macro inspiration into the lungs is considered the primary mechanism for development of nosocomial pneumonia. More than 90% of cases of nosocomial pneumonia are caused by bacteria, 15—30% represented with staphylococcus aureus. Following the data of a 4-year long period the resistance to methicillin was identified in ≈32% with a tendency of increasing percentage of MRSA isolates up to 35%, originated from samples taken among patients from ICU in the Clinical Center of Skopje

Orbital complications of acute rhinosinusitis

Introduction. Rhinosinusitis is the infection and inflammation of at least one of the 4 paranasal sinuses (frontal, maxillary, ethmoid and sphenoid). Their correct diagnosis is generally determined by examining the patient clinically and by rhinosinusal endoscopic examination. There are also cases that show complications or continued evolution despite the correct treatment, and then we will use some imaging investigations to find out more about affection(radiography of anterior sinuses of the face, sinus computerized tomography, sinus magnetic resonance imaging). In particular, acute rhinosinusitis should be carefully managed to avoid complications such as the local ones: orbital cellulitis, orbital abscess, osteomyelitis, cavernous sinus thrombosis; and intracranial complications: meningitis, epidural abscess, subdural abscess, cerebral abscess.Materials and methods. There will be presented all orbital complications according to the cases treated in the ENT Clinic of the Coltea Clinical Hospital.Conclusions. Diagnosis of rhinosinusitis is largely clinical and endoscopic.When complications of the condition arise, these should be investigated imagistically to determine their exact extent and to institute the correct treatment as soon as possible. The complications of rhinosinusitis are medical and surgical life-threatening emergencies, which is why in order to diagnose and correct and quickly institute therapy requires a multidisciplinary approach

Prostate cancer theranostics using GRPR antagonist RM26

The malignant transformation of cells is often associated with an alteration of their molecular phenotype, resulting in overexpression of several cell surface proteins. Gastrin-releasing peptide receptor (GRPR) and prostate-specific membrane antigen (PSMA) are examples of such pro-teins that are expressed at a high density in prostate cancer. GRPR is primarily expressed in earlier stages of prostate cancer and tends to decrease with disease progression. This expression pattern indicates that GRPR could be a promising target for imaging and treatment of oligometa-static prostate cancer, an early step in prostate cancer progression characterized by limited meta-static spread. In contrast, the expression of PSMA increases with cancer progression and is significantly upregulated as tumors dedifferentiate into higher grade, in androgen-insensitive and metastatic lesions. This thesis is based on five original articles (papers I-V) and focuses on the preclinical de-velopment of radiotracers for imaging and treatment of prostate cancer. The work can be divided into three distinct parts: (1) the development and optimization of GRPR-antagonist RM26 for high contrast PET and SPECT imaging of oligometastatic prostate cancer (papers I-III), (2) the preclinical evaluation of 177Lu-labeled RM26 as a potential candidate for peptide receptor radionuclide therapy (PRRT) in GRPR-expressing tumors, alone or in combination with anti-HER2 antibody trastuzumab (paper IV), and (3) the development of a bispecific heterodimer targeting both PSMA and GRPR in prostate cancer (paper V). We have demonstrated that the in vitro and in vivo properties of GRPR antagonist RM26 are strongly influenced by the choice of chelator-radionuclide complex and that long-lived radionuclides are desirable for high-contrast imaging. Furthermore, our data indicate that 55Co-NOTA-PEG2-RM26 has remarkable potential for next-day high-contrast PET imaging of GRPR-expressing tumors. Experimental PRRT using 177Lu-DOTAGA-PEG2-RM26 resulted in a pronounced inhibition of tumor growth and a significantly longer median survival. Interestingly, survival was further improved when trastuzumab was co-injected with 177Lu-DOTAGA-PEG2-RM26. These data indicate that blocking HER2 with trastuzumab decreased the repairing ability of irradiated cells. Finally, we developed a heterodimer (NOTA-DUPA-RM26) for imaging GRPR and PSMA expression in prostate cancer shortly after administration. In conclusion, we have successfully developed and preclinically evaluated radioconjugates for GRPR-directed theranostics in oligometastatic prostate cancer using the bombesin antagonistic analog RM26

Selection of optimal chelator improves the contrast of GRPR imaging using bombesin analogue RM26.

Bombesin (BN) analogs bind with high affinity to gastrin-releasing peptide receptors (GRPRs) that are up-regulated in prostate cancer and can be used for the visualization of prostate cancer. The aim of this study was to investigate the influence of radionuclide-chelator complexes on the biodistribution pattern of the 111In-labeled bombesin antagonist PEG2-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (PEG2-RM26) and to identify an optimal construct for SPECT imaging. A series of RM26 analogs N-terminally conjugated with NOTA, NODAGA, DOTA and DOTAGA via a PEG2 spacer were radiolabeled with 111In and evaluated both in vitro and in vivo. The conjugates were successfully labeled with 111In with 100% purity and retained binding specificity to GRPR and high stability. The cellular processing of all compounds was characterized by slow internalization. The IC50 values were in the low nanomolar range, with lower IC50 values for positively charged natIn-NOTA-PEG2-RM26 (2.6 ± 0.1 nM) and higher values for negatively charged natIn-DOTAGA-PEG2-RM26 (4.8 ± 0.5 nM). The kinetic binding studies showed KD values in the picomolar range that followed the same pattern as the IC50 data. The biodistribution of all compounds was studied in BALB/c nu/nu mice bearing PC-3 prostate cancer xenografts. Tumor targeting and biodistribution studies displayed rapid clearance of radioactivity from the blood and normal organs via kidney excretion. All conjugates showed similar uptake in tumors at 4 h p.i. The radioactivity accumulation in GRPR-expressing organs was significantly lower for DOTA- and DOTAGA-containing constructs compared to those containing NOTA and NODAGA. 111In-NOTA-PEG2-RM26 with a positively charged complex showed the highest initial uptake and the slowest clearance of radioactivity from the liver. At 4 h p.i., DOTA- and DOTAGA-coupled analogs showed significantly higher tumor-to-organ ratios compared to NOTA- and NODAGA-containing variants. The NODAGA conjugate demonstrated the best retention of radioactivity in tumors, and, at 24 h p.i., had the highest contrast to blood, muscle and bones

Prostate cancer theranostics using GRPR antagonist RM26

The malignant transformation of cells is often associated with an alteration of their molecular phenotype, resulting in overexpression of several cell surface proteins. Gastrin-releasing peptide receptor (GRPR) and prostate-specific membrane antigen (PSMA) are examples of such pro-teins that are expressed at a high density in prostate cancer. GRPR is primarily expressed in earlier stages of prostate cancer and tends to decrease with disease progression. This expression pattern indicates that GRPR could be a promising target for imaging and treatment of oligometa-static prostate cancer, an early step in prostate cancer progression characterized by limited meta-static spread. In contrast, the expression of PSMA increases with cancer progression and is significantly upregulated as tumors dedifferentiate into higher grade, in androgen-insensitive and metastatic lesions. This thesis is based on five original articles (papers I-V) and focuses on the preclinical de-velopment of radiotracers for imaging and treatment of prostate cancer. The work can be divided into three distinct parts: (1) the development and optimization of GRPR-antagonist RM26 for high contrast PET and SPECT imaging of oligometastatic prostate cancer (papers I-III), (2) the preclinical evaluation of 177Lu-labeled RM26 as a potential candidate for peptide receptor radionuclide therapy (PRRT) in GRPR-expressing tumors, alone or in combination with anti-HER2 antibody trastuzumab (paper IV), and (3) the development of a bispecific heterodimer targeting both PSMA and GRPR in prostate cancer (paper V). We have demonstrated that the in vitro and in vivo properties of GRPR antagonist RM26 are strongly influenced by the choice of chelator-radionuclide complex and that long-lived radionuclides are desirable for high-contrast imaging. Furthermore, our data indicate that 55Co-NOTA-PEG2-RM26 has remarkable potential for next-day high-contrast PET imaging of GRPR-expressing tumors. Experimental PRRT using 177Lu-DOTAGA-PEG2-RM26 resulted in a pronounced inhibition of tumor growth and a significantly longer median survival. Interestingly, survival was further improved when trastuzumab was co-injected with 177Lu-DOTAGA-PEG2-RM26. These data indicate that blocking HER2 with trastuzumab decreased the repairing ability of irradiated cells. Finally, we developed a heterodimer (NOTA-DUPA-RM26) for imaging GRPR and PSMA expression in prostate cancer shortly after administration. In conclusion, we have successfully developed and preclinically evaluated radioconjugates for GRPR-directed theranostics in oligometastatic prostate cancer using the bombesin antagonistic analog RM26

Radiolabeled GRPR Antagonists for Imaging of Disseminated Prostate Cancer - Influence of Labeling Chemistry on Targeting Properties

Background: Radionuclide molecular imaging of Gastrin-Releasing Peptide Receptor (GRPR) expression promises unparalleled opportunities for visualizing subtle prostate tumors, which due to small size, adjacent benign tissue, or a challenging location would otherwise remain undetected by conventional imaging. Achieving high imaging contrast is essential for this purpose and the molecular design of any probe for molecular imaging of prostate cancer should be aimed at obtaining as high tumor-to-organ ratios as possible. Objective: This short review summarizes the key imaging modalities currently used in prostate cancer, with a special focus on radionuclide molecular imaging. Emphasis is laid mainly on the issue of radiometals labeling chemistry and its influence on the targeting properties and biodistribution of radiolabeled GRPR antagonists for imaging of disseminated prostate cancer. Methods: A comprehensive literature search of the PubMed/MEDLINE, and Scopus library databases was conducted to find relevant articles. Results: The combination of radionuclide, chelator and required labeling chemistry was shown to have a significant influence on the stability, binding affinity and internalization rate, off-target interaction with normal tissues and blood proteins, interaction with enzymes, activity uptake and retention in excretory organs and activity uptake in tumors of radiolabeled bombesin antagonistic analogues. Conclusion: Labeling chemistry has a very strong impact on the biodistribution profile of GRPRtargeting peptide based imaging probes and needs to be considered when designing a targeting probe for high contrast molecular imaging. Taking into account the complexity of in vivo interactions, it is not currently possible to accurately predict the optimal labeling approach. Therefore, a detailed in vivo characterization and optimization is essential for the rational design of imaging agents. </jats:sec

Research Regarding the Development of the Combustion Chamber of Internal Combustion Engines with Opposite Pistons

The reduction in environment pollutant emissions is one of the main challenges regarding ground transportation. Internal combustion engines, used especially in hybrid propulsion systems, may be a solution in the transition to fully electric cars. Therefore, more efficient engines in terms of fuel consumption, emission generation and power density must be developed. This paper presents research regarding the architecture of the combustion chamber of an internal combustion engine with opposed pistons. The aim of this research was to find a combustion chamber architecture that would enable the engine to perform close to the program target of: NOx &lt; 3.5 g/kWh, smoke (FSN) &lt; 1, specific fuel consumption (bsfc) &lt; 198 g/kWh. Three variants of the combustion chamber’s architecture have been studied. After the experimental research, the conclusion was that none of them fully reached the target; however, significant improvements have been achieved compared with the starting point. As a result, further research needs to be carried out in order to reach and even exceed the target.</jats:p