Molecular modeling of Gram-positive bacteria peptidoglycan layer, selected glycopeptide antibiotics and vancomycin derivatives modified with sugar moieties.

Proper understanding of the mechanisms of binding to Gram-positive bacteria cell wall layers-especially to the peptidoglycan (PG) layer, seems to be crucial for proper development of new drug candidates which are effective against these bacteria. In this work we have constructed two different models of the Gram-positive bacteria PG layer: the layered and the scaffold models. PG conformational changes during geometry optimization, models relaxation, and molecular dynamics were described and discussed. We have found that the border surface of both PG layer models differs from the surface located away from the edge of models and the chains formed by disaccharide units prefer helix-like conformation. This curling of PG chains significantly affects the shape of antibiotic-accessible surface and the process is thus crucial for new drug development. Glycopeptide antibiotics effective against Gram-positive bacteria, such as vancomycin and its semisynthetic derivatives-oritavancin and telavancin, bind to d-alanyl-d-alanine stem termini on the peptidoglycan precursors of the cell wall. This binding inhibits cross-linking between the peptides and subsequently prevents cell wall synthesis. In this study some of the aspects of conformational freedom of vancomycin and restrictions from the modifications of vancomycin structure introduced into oritavancin and telavancin and five other vancomycin derivatives (with addition of 2-acetamido-2-deoxy-ß-d-galactopyranosylamine, 2-acetamido-2-deoxy-ß-d-glucopyranosylamine, 1-amine-1-deoxy-d-glucitol, 2-amino-2-deoxy-d-galactitol, or 2-amino-2-deoxy-d-glucitol to the C-terminal amino acid group in the vancomycin) are presented and discussed. The resulting molecular dynamics trajectories, root mean square deviation changes of aglycon and saccharide moieties as well as a comparative study of possible interactions with cyclic and chain forms of modified groups have been carried out, measured, and analyzed. Energetically advantageous conformations show close similarity to the structures known from the experimental data, but the diversity of others suggest very high conformational freedom of all modeled antibiotics and vancomycin derivatives. Alditol derivatives move closer to the peptidoglycan chain more easily but they also form intramolecular interactions more frequently than their homologous cyclic forms. One of the proposed derivatives seems to be a promising agent which is efficient in treatment of infections caused by Gram-positive bacteria.

[The case of otologic cerebrospinal fluid leak in patient with recurrent meningeal infection]. / Przypadek plynotoku usznego u chorej z nawracajacymi zapaleniami opon mózgowo-rdzeniowych.

The authors present a cause of 51 year old female with recurrent meningeal infection. The patient had a remote history of head injury that she had almost forgotten. CT was performed but no pathology of temporal bone origin was diagnosed. DTPA+Tc99m cisternography showed an abnormal radioactive accumulation in the right middle ear at 6 and 24 hours after intrathecal injection.

[Intracranial complications of sinusitis in patients of the otolaryngology Department of the regional hospital in Olsztyn treated between 2004-2007]. / Wewnatrzczaszkowe powiklania zatokopochodne u pacjentów Oddzialu Otolaryngologicznego Szpitala Wojewódzkiego w Olsztynie leczonych w Latach 2004-2007.

Sinusitis is common disease. However intracranial complications of sinusitis are rare, but they are still a serious problem that results in high mortality. Diagnostic advantages of CT scanning and magnetic resonance imaging as well as therapeutic advantages of FESS prevent spread of complications. Patients with intracranial complications require surgery to remove the focus of infection from the sinuses and neurosurgical drain the abscess in some cases, with intensive antibiotic therapy. We presented three cases of intracranial complications treated by endoscopic sinus surgery connected with extranasal drain of frontal sinus. It is worth to emphasize the advantages of FESS over the external approaches as follows: the method treats the causative source of the disease, the morbidity is low, and it avoids facial cosmetic trauma.

[Malignant melanoma of the auditory tube]. / Przypadek czerniaka zlosliwego trabki sluchowej.

Melanomas of the mucous membranes of airway tract constitute around 1% of the total melanomas of head and neck. The most common site of the tumor are the nasal and paranasal sinuses but melanomas of the oral cavity are described too. The location of malignant melanoma in the eustachian tube is very rare. We found five cases of this disease in the literature. In our article we present a 53-year-old woman with progressive left aural fullness and hearing impairment for two months. Clinical examination found left middle ear effusion. The nasopharyngoscopy revealed a bluish red, friable and granulomatous tumor occupying the whole pharyngeal orifice of the left auditory tube. The biopsy speciment was taken which established the diagnosis. Because of localization and spread of the melanoma we had a low opinion of surgical treatment and radiotherapy was recommended. The patient was under constant laryngologic and oncological observation. We did not notice the local recurrence of melanoma. She died two years after making the diagnosis because of the neoplasm dissemination.

[Case of esophageal foreign body complicated by mediastinitis and broncho-esophageal fistula]. / Przypadek ciala obcego przelyku powiklany zapaleniem sródpiersia i przetoka przelykowo-oskrzelowa leczony pomyslnie.

Authors describe the case of esophageal perforation in 85-year woman ended with good outcome. The patient was admitted to our ward with suspicion of foreign body in esophagus and the clinical manifestation of early stage mediastinitis. We resigned esophageal perforation debridement because of the old age and patient's poor general condition. Conservative treatment was administrated during a long period including high-doses of antibiotics and nutritional support. In the third week of patient's admission mediastinitis was cured but esophageal radiograms showed the bronchoesophageal fistula on the left side. There were no signs of self-existent closure of fistula. The patient was sent to the Thoracic Surgery Ward of John Paul Hospital in Cracow where the performance of thoracotomy was used as surgical treatment. Closure of fistula made that our patient was able to return to normal life.

[Parapharyngeal phlegmon as a complication after tonsillectomy]. / Ropowica przestrzeni przygardlowej jako powiklanie po tonsylektomii.

Authors wanted to draw attention to possibility of dangerous postoperative complications when the clinical manifestation of reactivation Herpes simplex virus infection develops during the postoperative period. We report a case of parapharyngeal phlegmon following tonsillectomy in a previously healthy 18-year old woman. On postoperative day six signs of Herpes simplex virus infection were presented in our patient. Hypoimmunity causing reactivation of virus led to evolution of septicemia and extended parapharyngeal phlegmon. Management involved parapharyngeal space drainage, broad spectrum antibiotics and gammaglobulin coverage. Treatment was successful. The patient was discharged in good condition in the fourth week of her admission.

[Tuberculosis of the inner ear]. / Gruzlica ucha srodkowego.

Tuberculosis of the middle ear is a rare, but not a nonexistent disease. It is well reported in literature that the typical features of this disease have been changing over the years, what can lead to delay in proper diagnosis and cause irreversible complications. Presented two cases of tuberculous otitis media confirm the opinion that historically classical triad of features: painless otorrhea, multiple perforations of the tympanic membrane and concomitant peripheral facial paralysis is often absent in the clinical picture of this disease.