Presence of different genotypes of Helicobacter pylori in patients with chronic tonsillitis and sleep apnoea syndrome

Helicobacter pylori, a well-known gastric pathogen, has been detected in the oral cavity and oropharynx in tonsillar tissue. In our study, the presence of H. pylori in the tonsillar tissue of patients with chronic tonsillitis and sleep apnoea syndrome (SAS) was investigated. The aim was to detect and genotype H. pylori for a collection of data supporting the possible role of H. pylori in the aetiology of chronic tonsillitis and SAS. Helicobacter pylori was detected by real-time polymerase chain reaction (rt-PCR). 89 patients, 60 with a diagnosis of chronic tonsillitis and 29 with SAS, were tested. In the chronic tonsillitis group, Helicobacter was detected in 48 (80 %) specimens, cagA gene was detected in 12 samples (25 %) and 12 samples were negative. In SAS group, Helicobacter was found in 24 samples (82.76 %), cagA gene was detected in 5 (20.83 %) and 5 samples (17.24 %) were negative. Helicobacter pylori-specific immunoglobulins were tested by ELISA in the serum of 57 patients only with 41 (71.93 %) showing positive. Our results on H. pylori DNA detection and H. pylori seropositivity show 26.32 % discrepancy, slightly in favour of rt-PCR (15.79 % compared to 10.53 %). The H. pylori presence in tonsillar tissue does not depend on the type of oropharyngeal disease (p = 0.756). This study shows that oropharynx constitutes an extragastric reservoir of H. pylori infection which could serve as an aetiopathogenetic factor for chronic tonsillitis and tonsillar hyperplasia by SAS. No conclusion has yet been drawn about the mechanism of the process.     

Targeted Endodontic Microsurgery: Implications of the Greater Palatine Artery

IntroductionTargeted Endodontic Microsurgery (TEMS) combines trephine burs and 3D-printed guides to make flapless maxillary palatal root-end surgery possible. This study assessed the location of the greater palatine artery (GPA), the relationship of the GPA to maxillary molar root ends, and the feasibility of flapless palatal-approach TEMS.MethodsThree endodontists analyzed 250 cone-beam computed tomographic images of maxillary molars for (1) transition morphology between the hard palate and the alveolar process adjacent to first and second molars as an indication of the most likely location of the GPA, (2) the superior-inferior relationship between the GPA and root ends, and (3) the feasibility of palatal-approach TEMS.ResultsPalatal transition morphology included 20% Spine, 72% Bridge, and 8% Smooth. GPA position as related to palatal root ends was classified as 34% superior, 40% adjacent, and 21% inferior. Five percent of classifications were undefined. TEMS was deemed feasible for 47% of maxillary first molars and 52% of second molars, and was significantly more feasible with GPAs superior to palatal root ends. Reasons for infeasibility included GPA proximity and unfavorable resection angle or level. Maxillary first molar palatal roots were 11.13 ± 2.68 mm from the greater palatine foramen (GPF) and 2.37 ± 1.46 mm from the GPA. Second molar palatal roots were 4.94 ± 2.55 mm from the GPF and 2.53 ± 1.77 mm from the GPA.ConclusionsPalatal transition morphology and GPA position adjacent to maxillary molars, as manifested in cone-beam computed tomographic coronal views, suggested maxillary palatal root TEMS could be accomplished with a 2-mm safety margin in 47% of first molars and 52% of second molars. Historical paradigms that do not consider flapless palatal surgical approaches may need to be revised.     

Histopathology Image Analysis in Two Long‐Term Animal Experiments with Helical Flow Total Artificial Heart

Histopathological analysis can provide important information in long‐term experiments with total artificial heart (TAH). Recently, a new type of blood pump, the helical flow total artificial heart (HF‐TAH) was developed. This study aimed to investigate the changes in selected vital organs in animal experiments with implanted HF‐TAH. Samples from lung, liver, and kidneys from two female goats (No. 1301 and No. 1304) with implanted HF‐TAH were analyzed. Tissue samples were fixed in 10% formaldehyde and 4 µm thick transverse sections were stained with hematoxylin‐eosin (HE). Additional staining was done for detection of connective tissue (Masson‐Goldner stain) and for detection of iron (hemosiderin) deposits (Perls stain). Sections were scanned at 100× and 500× magnification with a light microscope. Experiment no. 1301 survived 100 days (cause of termination was heavy damage of the right pump); experimental goat no.1304 survived 68 days and was sacrificed due to severe right hydrodynamic bearing malfunction. Histopathological analysis of liver samples proved signs of chronic venostasis with limited focal necrotic zones. Dilated tubules, proteinaceous material in tubular lumen, and hemosiderin deposits were detected in kidney samples. Contamination of the organs by embolized micro‐particles was suspected at the autopsy after discovery of visible damage (scratches) of the pump impeller surface (made from titanium alloy) in both experiments. Sporadic deposits of foreign micro‐particles (presumably titanium) were observed in most of the analyzed parenchymal organs. However, the described deposits were not in direct connection with inflammatory reactions in the analyzed tissues. Histopathological analysis showed the presence of minimal contamination of the lung, kidney, and liver tissue samples by foreign material (titanium very likely). The analysis showed only limited pathological changes, especially in liver and kidneys, which might be attributed to the influence of artificial perfusion often observed in chronic TAH experiments.     

Eine tödliche Vergiftung durch Glykosal als Folge einer “Rezeptsünde”

Ohne Zusammenfassung     

Elevated intrathecal antibodies against the medium neurofilament subunit in multiple sclerosis

Neurofilaments are cytoskeletal proteins localized within axons, which may interact with the immune system during and following tissue destruction in multiple sclerosis (MS). Antibodies against the medium neurofilament subunit synthesized intrathecally may reflect axonal damage in MS patients. Both immunoglobulin G (IgG) and M (IgM) responses against the purified native medium subunit of neurofilaments (NFM) using enzyme-linked immunosorbent assay (ELISA) were determined in paired serum and cerebrospinal fluid samples obtained from 49 MS patients, 16 normal controls (CN), 21 control patients with miscellaneous diseases (CD) and 14 patients with neurodegenerative disorders (CDEG). Intrathecal production of IgM and IgG antibodies to NFM were elevated in MS patients compared with the CN or CD groups (p < 0.04 for IgM, p < 0.01 for IgG). The increase was present in all the MS courses (relapsing-remitting, primary and secondary progressive). Similar local anti-NFM IgG and IgM synthesis occurred in the MS and CDEG groups. MS patients with short and long disease duration did not differ in terms of their anti-NFM IgM and IgG responses. Repeated examinations showed stable intrathecal anti-NFM production. Intrathecal IgG and IgM antibodies against NFM were increased in MS patients and may serve as a potential marker for axonal pathology. The extent of anti-NFM levels did not correspond to any individualized clinical profiles of MS patients.     

Leukotrienes B4, C4, D4 and E4 in the Exhaled Breath Condensate (EBC), Blood and Urine in Patients with Pneumoconiosis

Leukotrienes (LTs) are involved in the pathogenesis of lung fibrosis and were increased in exhaled breath condensate (EBC) of the patients with pneumoconiosis. However the possible influence of extra-pulmonary disorders on the EBC markers is not known. Therefore in parallel with EBC, LTs' levels in the plasma and urine were measured in patients with pneumoconiosis (45 × asbestos exposure, 37 × silica exposure) and in 27 controls. Individual LTs B4, C4, D4 and E4 were measured by liquid chromatography - electrospray ionization - tandem mass spectrometry (LC-ESI-MS/MS). In EBC, LT D4 and LT E4 were increased in both groups of patients (p<0.001 and p<0.05), comparing with the controls. Both LT B4 and cysteinyl LTs were elevated in asbestos-exposed subjects (p<0.05). Asbestosis with more severe radiological signs (s1/s2-t3/u2) and lung functions impairment has shown higher cysteinyl LTs and LT C4 in the EBC (p<0.05) than mild asbestosis (s1/s0-s1/s1). In addition, in the subjects with asbestosis, cysteinyl LTs in EBC correlated with TLC (-0.313, p<0.05) and TLCO/Hb (-0.307, p<0.05), and LT C4 with TLC (-0.358, p<0.05). In pneumoconioses, EBC appears the most useful from the 3 fluids studied.     

From nonpeptide toward noncarbon protease inhibitors: metallacarboranes as specific and potent inhibitors of HIV protease

HIV protease (PR) represents a prime target for rational drug design, and protease inhibitors (PI) are powerful antiviral drugs. Most of the current PIs are pseudopeptide compounds with limited bioavailability and stability, and their use is compromised by high costs, side effects, and development of resistant strains. In our search for novel PI structures, we have identified a group of inorganic compounds, icosahedral metallacarboranes, as candidates for a novel class of nonpeptidic PIs. Here, we report the potent, specific, and selective competitive inhibition of HIV PR by substituted metallacarboranes. The most active compound, sodium hydrogen butylimino bis-8,8-[5-(3-oxa-pentoxy)-3-cobalt bis(1,2-dicarbollide)]di-ate, exhibited a K(i) value of 2.2 nM and a submicromolar EC(50) in antiviral tests, showed no toxicity in tissue culture, weakly inhibited human cathepsin D and pepsin, and was inactive against trypsin, papain, and amylase. The structure of the parent cobalt bis(1,2-dicarbollide) in complex with HIV PR was determined at 2.15 A resolution by protein crystallography and represents the first carborane-protein complex structure determined. It shows the following mode of PR inhibition: two molecules of the parent compound bind to the hydrophobic pockets in the flap-proximal region of the S3 and S3' subsites of PR. We suggest, therefore, that these compounds block flap closure in addition to filling the corresponding binding pockets as conventional PIs. This type of binding and inhibition, chemical and biological stability, low toxicity, and the possibility to introduce various modifications make boron clusters attractive pharmacophores for potent and specific enzyme inhibition.