Quinoline Compounds Targeting the c-Ring of ATP Synthase Inhibit Drug-Resistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa (PA) is a Gram-negative, biofilm-forming bacterium and an opportunistic pathogen. The growing drug resistance of PA is a serious threat that necessitates the discovery of novel antibiotics, ideally with previously underexplored mechanisms of action. Due to their central role in cell metabolism, bacterial bioenergetic processes are of increasing interest as drug targets, especially with the success of the ATP synthase inhibitor bedaquiline to treat drug-resistant tuberculosis. Like Mycobacterium tuberculosis, PA requires F1Fo ATP synthase for growth, even under anaerobic conditions, making the PA ATP synthase an ideal drug target for the treatment of drug-resistant infection. In previous work, we conducted an initial screen for quinoline compounds that inhibit ATP synthesis activity in PA. In the present study, we report additional quinoline derivatives, including one with increased potency against PA ATP synthase in vitro and antibacterial activity against drug-resistant PA. Moreover, by expressing the PA ATP synthase in Escherichia coli, we show that mutations in the H+ binding site on the membrane-embedded rotor ring alter inhibition by the reported quinoline compounds. Identification of a potent inhibitor and its probable binding site on ATP synthase enables further development of promising quinoline derivatives into a viable treatment for drug-resistant PA infection.

[Experiences in the treatment of midfacial fractures using a fixed-angle osteosynthetic system. Biomechanical results]. / Osteosynthetische Versorgung von Mittelgesichtsfrakturen mit einem multidirektionalen winkelstabilen Plattensystem. Biomechanische Ergebnisse.

AIM: Fixed-angle osteosynthetic systems are characterized by mechanical "locking" of the osteosynthetic screw and plate. These systems have found increasing acceptance and use for osteosynthetic fixation and temporary reconstruction of the mandible. The aim of this study was to investigate the applicability and performance of fixed-angle systems in the treatment of midfacial fractures. MATERIAL AND METHOD: A newly developed fixed-angle osteosynthetic plate system (smart lock) was compared to a conventional system using fresh human skulls. The iatrogenically produced zygomatic fractures of the human skulls were treated by osteosynthesis and biomechanically tested. Furthermore, in a dynamic test series, an artificial bone was subjected to an alternating force of 15 N of up to 1,000,000 cycles. The new screws and plates were subjected to further biomechanical tests. RESULTS: The tests using the fixed-angle implants revealed that an increase of stability of up to 40% can be expected after osteosynthetic fixation. Furthermore, the plates resisted 1,000,000 cycles of alternating forces, whereby the conventional systems failed after 170,000 cycles on the average. CONCLUSION: Fixed-angle systems, due to their construction, provide a high degree of stability even in thin bones of the midface. They appear to be promising for the treatment of midfacial fractures.

Digital transversal slice imaging in dental-maxillofacial radiology: from pantomography to digital volume tomography.

With digital transversal slice imaging (TSI) as a supplementary program to pantomographic devices and digital volume tomography (DVT), images of the viscerocranium are now possible in several planes. The two procedures, TSI and DVT, are complementary. They should be applied where the indication justifies it in dentistry and maxillofacial surgery for diagnostic and forensic purposes. To minimize patient exposure to radiation, computer tomography (CT) should only be used in complex situations of the viscerocranium where soft tissues are involved or in tumor diagnosis.

[Clinical outcome of re-innervation of radial flaps and latissimus dorsi muscle transplants]. / Klinische Ergebnisse der Resensibilisierung von Radialislappen und Musculus-latissimusdorsi-Transplantaten.

BACKGROUND: The necessity of nerve anastomosis in an attempt to regain cutaneous sensitivity following flap transfer has been the basis of many discussions. In our study, we investigated the degree of sensory recovery with emphasis on the different nerval qualities on the radial forearm and the latissimus dorsi flap. COLLECTIVE: Sixty-two patients with 66 latissimus dorsi flaps and 19 patients with a radial forearm free flap were examined. RESULTS: Except for five latissimus dorsi and two radial forearm flaps, all flaps investigated showed clinical signs of sensory recovery, whereby the degree and quality of cutaneous reinnervation varied. In comparison, neural reconstruction did not lead to any clinical improvement. CONCLUSION: Based on our clinical results, we consider nerve reconstruction during radial forearm and latissimus dorsi free flap transfer unnecessary. To what extent this can be said for other flaps requires further investigation.

[Initial results using extracorporeal low energy shockwave therapy ESWT in muscle reflex-induced lock jaw]. / Erste Erfolge unter Anwendung der extrakorporalen niederenergetischen Stosswellentherapie ESWT bei muskelreflektorischer Kieferklemme.

BACKGROUND: Post-traumatic reflex-mediated temporomandibular joint (TMJ) locking is one of the complications frequently observed after sophisticated and long dentoalveolar operations. Its severity can be up to 90%. Usually, therapy consists of mouth-opening exercises using tongue depressors. In difficult cases, the treatment regularly extends for weeks, often with only moderate improvement of this painful limitation. USE OF ESWT: In three cases, it was shown that supportive treatment utilizing low-energy shock waves (ESWT) is significantly effective in the therapy of limited opening of the mouth. The patients reported relief of their complaints, especially over the mandibular angle region, through the daily application of ESWT and felt their condition improved after the fifth therapy course. DISCUSSION: This in particular improved the patient's ability to eat, speak, and maintain good oral hygiene. Great physiotherapeutic benefit is imparted by the use of ESWT in the clinical management of these and other cases of dentomaxillofacial practice.

Clinical and histological results of sensory recovery after radial foreann flap transfer.

The necessity of nerve anastomosis in an attempt to regain dermal sensitivity following pedicled or free-flap transfer has been the basis of many discussions. In our study, we investigated the degree of sensory recovery with emphasis on the different nerval qualities, on the radial forearm flap and correlated it to the histological and immunohistological findings. Nineteen patients with radial forearm free flap--five of whom underwent nerve anastomosis--were examined. The follow-up interval was 20.3 months (average) after surgical intervention. Histological examinations were performed on 13 of the 19 patients, in eight cases on one occasion and in five on more than one occasion. Seventeen patients experienced sensory recovery, whereby the degree and quality of dermal innervation varied. In comparison, the nerval reconstruction did not lead to any significant improvement. Based on our clinical results, we regard the nerve reconstruction during the radial forearm free flap transfer as unnecessary. To what extent this can be said for other flaps demands further investigation.

[Acute temporomandibular joint arthritis after Lyme borreliosis]. / Akute Kiefergelenkarthritis nach Lyme-Borreliose.

CASE REPORT: This report is about a rare connection between Lyme disease and an inflammation of the left temporomandibular joint. In this case, an infection was documented in 1998, 5 years after contact with Borrelia burgdorferi. The patient, a 49-year-old female, first came to our department in 1999. She showed the symptoms of a left temporomandibular joint infection. THERAPY: We suggested treatment with ceftriaxone 1 x 2 g/day i.v.

[Titanium magnets on implants as an aid in rehabilitation after tumor treatment]. / Titanmagnete auf Implantaten als Hilfsmittel zur Rehabilitation nach Tumorbehandlung.

After the resection of a tumor, many patients need a reconstruction with hard and soft tissue and also with sufficient dentures. Often, only little space is available for the implantation. Implant length and diameter have to be reduced, and the result is a change in the biomechanics with a possible mechanical overloading of the implant. We examined 52 tumor patients undergoing reconstruction with 189 implants. A new concept involving attachment with the help of magnets is presented, offering a satisfactory solution in these difficult cases after tumor resection and reconstruction.

[Primary solitary malignant schwannoma of the trigeminal nerve, Report of a case and review of the literature]. / Primär solitäres malignes Schwannom des N. trigeminus. Fallbericht mit Literaturübersicht.

We present the case of a primary solitary malignant schwannoma of the trigeminal nerve. A total of 55 cases have been described in the literature; however, in these cases two tumors were affecting the supraorbital branch. This nerve-sheath tumor usually affects men in the fifth decade of life. The main clinical sign of malignant schwannomas of the head and neck is an indolent swelling. Hematogenic or lymphogenic metastasis has not been described. Because of the pleomorphism of the tumor cells immunohistochemical study is important. The treatment of choice is radical resection, possibly with adjuvant radio- or chemotherapy. The 5-year survival rate of malignant schwannoma of the trigeminal nerve is 41.7%.

[Clear cell odontogenic carcinoma in connection with squamous epithelial carcinoma. Case report and review of the literature]. / Hellzelliges odontogenes Karzinom in Verbindung mit einem Plattenepithelkarzinom. Fallbericht und Literaturübersicht.

One case of a newly described, rare odontogenic tumor is reported. A literature review of 19 cases lends support to the odontogenic origin and metastatic capability, both regionally and distantly, of the clear cell odontogenic tumor. We conclude that this tumor is malignant, with a tendency to recur locally after surgery. It requires an aggressive surgical approach and should be referred to as a clear cell odontogenic carcinoma. In our patient we saw a clear cell odontogenic carcinoma and a squamous cell carcinoma, both with regional lymph node metastasis. The histological differentiation of this type of tumor from other clear cell tumors is difficult.

[Detection of human papillomavirus (HVP)-DNA in oral manifestation of lichen planus]. / Nachweis humaner Papillomavirus (HPV)-DNA bei oraler Manifestation von Lichen planus.

Human papilloma viruses (HPV) can be detected in different epithelia with the help of the polymerase chain reaction (PCR). The role of HPV in the development of anogenital cancers has been intensively studied, and current evidence shows that most cervical cancers are associated with so-called high risk HPV types (e.g. HPV 16 and 18). HPV-infections can also be demonstrated in oral premalignant lesions and squamous cell carcinomas. Depending on the sensitivity of the detection method, 40-67% of leukoplakias, 2.5-76% of squamous cell carcinomas and 0-87% of cases of lichen planus were described to be infected with HPV 16 or 18. Whether lichen planus can be considered as a premalignant lesion is still controversial. By the use of PCR and hybridization we found infections with the high risk HPV types 16, 18 and 31 in 42% (3/7) of the patients with lichen planus. Further investigations with a higher numbers of cases in combination with the analysis of the viral gene expression as well as the clinical and histological control of the corresponding regions are necessary. The aim of these studies is to find out the prognostic value of the HPV infection for this facultative premalignant disease.

[Mandibular collum fracture in the ultrasound image--indications and limits from the viewpoint of 3 years imaging experiences]. / Die Kollumfraktur im Ultraschallbild--Indikation und Grenzen aus der Sicht von drei Jahren Anwendungserfahrung.

The Ultrasound technique as an image producing procedure for fractures of the mandibular collum is outlined with physical theory and clinical examples. Advantages and disadvantages are compared and it is stated that a part of all patients with fractures might have a benefit from this method. Mentally handicapped patients, pregnant women and all sorts of fidgety patients will profit by the ultrasound investigation as the only way to ascertain the bone-fracture. There is necessity to relate the sonogram to a conventional X-ray picture whenever it is possible, for the procedure is suited to prove the fracture, not to exclude it.

[Diagnosis and differential diagnosis of sialo-odontogenic (glandular-odontogenic) cyst]. / Diagnose und Differentialdiagnose der sialoodontogenen (glandulär-odontogenen) Zyste.

Sialo-odontogenic (glandular-odontogenic) cyst is a new entity in the classification of developmental epithelial odontogenic cysts. Differentiation of this type of odontogenic cysts from dentigerous cysts and keratocysts and also from cystic mucoepidermoid carcinoma is essential. A sialo-odontogenic (glandular-odontogenic) cyst is likely to show aggressive growth, so that complete resection is essential. We demonstrate sialo-odontogenic (glandular-odontogenic) cyst by presenting four new cases and differentiate it from a special type of odontogenic keratocyst and a typical cystic mucoepidermoid carcinoma.

Physiological evidence that the primary site of auxin action in maize coleoptiles is an intracellular site.

To locate functionally the primary site of auxin action in growing cells, the pool of auxin relevant to induction of growth in maize (Zea mays L.) coleoptile sections was determined. A positive correlation was consistently noted between growth and intracellular levels of indole-3-acetic acid (IAA), i.e. growth appears to be relatively independent of the external level of IAA. N-1-Naphthylphthalamic acid (NPA), a potent inhibitor of auxin transport, was used to enhance accumulation of IAA in coleoptile cells. From the use of NPA, it is shown that: 1) increasing the accumulation of IAA in cells, while the external concentration is held constant, resulted in a concomitant increase in growth, and 2) blocking the exit of IAA from cells with NPA sustained an IAA-induced growth response in the absence of externally applied IAA. Furthermore, the absence of any alterations in auxin binding to microsomal fractions by NPA indicates that the action of NPA in causing enhancement of auxin-induced growth is based upon its inhibition of efflux of IAA from the cells.

Binding of a major secretory protein from bull seminal vesicles to bovine spermatozoa.

The seminal vesicles synthesize in an androgen-dependent manner a neutral protein of 13.5 kDa molecular weight that makes up about 40% of their secretion ("major protein"). An antiserum against this protein raised in rabbits was used to localize the antigen within the seminal vesicles. In addition to intraluminal secretion of the seminal vesicles and the ampulla of the vas deferens, ejaculated and ampullary spermatozoa revealed an intense immunoreaction, which was restricted to the neck region of the sperm head and the middle piece, while the principal piece of the tail as well as the sperm head were devoid of immunoreactive material. Comparison of spermatozoa taken from the tail of the epididymis with ampullary spermatozoa showed that about 90% of the latter, but only 10-20% of the former presented this distributional pattern of immunoreactive sites. Epididymal epithelium as well as calf seminal vesicle epithelium showed no immunoreactivity with major protein antiserum. Using a pre-embedding staining technique with gold-labeled primary or secondary antibodies, respectively, no immunostaining could be achieved at the ultrastructural level. Incubation experiments of epididymal spermatozoa in EGTA-containing solutions in the absence of calcium resulted in a gradual labilization and eventual loss of the plasma membrane of the sperm middle piece. After removal of (at least part of) the plasma membrane, bound major protein could be visualized immunohistochemically close to the mitochondria of the middle piece using a gold-labeled primary or secondary antibody. The acceptor site for major protein therefore seems to reside inside the plasma membrane of the sperm middle piece.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of a pH-response curve for growth to predict apparent wall pH in elongating segments of maize coleoptiles and sunflower hypocotyls.

To determine the relationship between apparent pH of the wall solution and shoot segment elongation, curves for the initial growth rates as a function of pH of the external solution were determined for maize (Zea mays L.) coleoptiles and sunflower (Helianthus annuus L.) hypocotyls and used to predict apparent wall pH in segments responding to indole-3-acetic acid (IAA) and fusicoccin (FC). When a solution having a pH predicted for walls of coleoptile segments responding to IAA was applied to the segments in the presence of IAA, this pH was not maintained. However, when the same was done for coleoptile segments responding to FC, the predicted pH was maintained in the external solution. Sunflower hypocotyl tissue did not maintain the external pH at the predicted value in the presence of either IAA or FC. The results indicate that wall loosening in coleoptiles caused by IAA may not be solely controlled by pH in the wall, yet growth (wall loosening) caused by FC apparently is directly related to wall pH. In sunflower the growth response to neither IAA nor FC appears to be directly correlated with wall pH.

An Improved Method for Detecting Auxin-induced Hydrogen Ion Efflux from Corn Coleoptile Segments.

Conditions necessary to detect maximal auxin-induced H(+) secretion using a macroelectrode have been investigated using corn coleoptile segments. Auxin-induced H(+) secretion is strongly dependent upon oxygenation or aeration when the tissue to volume ratio is high. Cuticle disruption or removal is also necessary to detect substantial auxin-induced H(+) secretion. The auxin-induced decrease in pH of the external medium is stronger when the hormone is applied to tissue in which the cuticle has been disrupted with an abrasive than when the hormone is applied to tissue from which the cuticle and epidermis have been removed by peeling. The lower detectable acidification of the external medium when using peeled segments appears to be due in part to the leakage of buffers into the medium and in part to the removal of the auxin-sensitive epidermal cells.The sensitivity of corn coleoptile segments to auxin, as measured by H(+) secretion, increases about 2-fold during the first 2 hours after excision. This change in apparent sensitivity to auxin as reflected by H(+) secretion is paralleled by a time-dependent change in the growth response to auxin. Under optimal conditions for detecting H(+) efflux (oxygenation, abrasion, hormone application 2 hours after excision), the latent period in auxin-induced H(+) efflux (about 7 or 8 minutes) is only half as great as the latent period in auxin-induced growth (about 18 to 20 minutes). These observations are consistent with the acid growth hypothesis of auxin action.

Auxin action on proton influx in corn roots and its correlation with growth.

At concentrations inhibitory to the elongation of corn (Zea mays L.) roots, the auxins, indole-3-acetic acid (IAA) and α-naphthaleneacetic acid (α-NAA), cause an increase in the pH of the bathing medium; this increase occurs with an average latent period shorter than the latent period for the inhibitory effect of these auxins on elongation. Indole-2-carboxylic acid, an inactive structural analogue of IAA, and ß-naphthaleneacetic acid, an inactive analogue of α-NAA, affect neither growth nor the pH of the medium. Since acid pH is known to promote and basic pH to inhibit root elongation, the data are consistent with the hypothesis that hormone-induced modification of cell-wall pH plays a role in the control of elongation of roots, as has been proposed for elongation of stems and coleoptiles.

Nonhormonal induction of H efflux from plant tissues and its correlation with growth.

When the esterase substrate alpha-naphthyl acetate is added to segments from coleoptiles of oat (Avena sativa L., var. Victory) or corn (Zea mays L., Bear hybrid WF 9 x 38) or to roots of lentil (Lens culinaris Med.), it is rapidly taken up and hydrolyzed to alpha-naphthol and acetic acid. This technique was used to generate intracellular acid and to study the effect of its efflux on growth. With corn coleoptile segments, treatment with alpha-naphthyl acetate induced more rapid and more prolonged growth than did exposure to external acidic buffers. Dose-response studies of alpha-naphthyl acetate induction of H(+) secretion and growth indicated the existence of a distinct threshold rate of H(+) efflux below which growth is not enhanced. The rate of H(+) efflux induced by optimal levels of auxin appears to be at or below this threshold level in corn coleoptile tissue. These data indicate that the relationship between external acidification and elongation is not a simple one and that the effectiveness of H(+) entering the cell wall may depend on factors not directly correlated with the appearance of H(+) in the external medium.

Time-dependent Changes in the Auxin Sensitivity of Coleoptile Segments: Apparent Sensory Adaptation.

When segments are excised from corn (Zea mays L.) coleoptiles they exhibit a very low rate of elongation for about 3.5 hours. A strong increase in growth rate (the spontaneous growth response) then occurs and persists for many hours. During the latent period preceding the spontaneous growth response there is an apparent increase with time in the sensitivity of the segments to indoleacetic acid (IAA). This increase in sensitivity is expressed as a 2- to 3-fold increase in the magnitude of the growth response to low levels of IAA and a 3-fold decrease in the latent period of the response during the first 3 hours following excision. A similar increase in sensitivity to low levels of IAA is noted if application of IAA is timed from the point of termination of a previous exposure to the hormone. Since the increase in responsiveness to low levels of IAA is not paralleled by an increase in the rate of uptake of the hormone, the data may be interpreted as evidence for a type of time-dependent sensory adaptation to auxin. The IAA dose-response relationship also changes with time, and there is indirect evidence that an auxin-dependent inhibitor may influence the expression of the apparent sensory adaptation to auxin.