Synthesis, antibacterial activities, and pharmacological properties of enantiomers of temafloxacin hydrochloride.

Temafloxacin hydrochloride [(+/-)-7-(3-methylpiperazin-1-yl)-6-fluoro-1-(2,4-difluorophenyl)- 1,4-dihydro- 4-oxoquinoline-3-carboxylic acid hydrochloride] is a potent member of the 4-pyridone-3-carboxylic acid class of antibacterial agents and is currently under clinical development as a broad-spectrum antimicrobial agent. It is a racemate having a chiral center at the C3 of the 7-piperazin-1-yl group. The two enantiomers were synthesized and tested for their antibacterial activities. Although no difference in in vitro antibacterial activities was observed, a minor difference in in vivo antibacterial activities was observed. However, they both exhibited similar pharmacological profiles.     

(Aminomethyl)arloxy]acetic acid esters. A new class of high-ceiling diuretics. 3. Variation in the bridge between the aromatic rings to complete mapping of the receptor

Continued structural evaluation of the [(aminomethyl)aryloxy]acetic ester diuretics has produced a series of compounds in which the functional group that bridges the two aromatic rings has been varied. Diuretic screening of these analogues in rats indicates that the keto group can be effectively replaced with an ether or thio ether function with a slight increase in potency, whereas the methylene and sulfoxide linking groups lead to diminished saluretic potency. Replacement with either -SO2-, -COCO-, -CH2O-, -CONH- or direct bond results in a loss of activity. Although the series was designed according to QSAR criteria, the traditional linear free-energy properties of these compounds do not correlate with diuretic potency. However, conformational analysis of the series by potential energy calculations indicates that all active compounds have an accessible conformation that matches the bridge atom-carboxylate distance of the very potent dihydrobenzofuran analogue 56. Conformational calculations of several compounds in which the aminomethyl group was varied suggests that the active conformation is probably a low-energy conformation. Consideration of rotation about the bridge could not distinguish between two possible orientations of the aminomethyl ring in the active conformation. However, there is a quantitative negative linear correlation between diuretic potency and the protrusion into space of the group that bridges the two aromatic rings.     

Analgesic and tranquilizing activity of 5,8-disubstituted 2-aminomethyl-3,4-dihydronaphthalenes

Interesting analgesic activity approaching that of meperidine and codeine was observed in standard animal models for 8-chloro-3,4-dihydro-5-methoxy-2-pyrrolidinomethylnaphthalene (compound 7). This compound was orally effective and its analgesic activity was not reversed by the opiate antagonist, naloxone. A limited number of other 2-aminomethyl analogues displayed activity in neuroleptic screens.     

Thermography as a means for quantitative assessment of stump and phantom pains

Exact differentiation into stump and phantom pain is required when pain is reported after amputation. In a majority of cases appropriate treatment can improve the pain. Thermography is simple and gives a good indication of the circulation in the stump without operative intervention. It provides a key to the nature of the pain in stump and phantom. Although typical patterns occur for pain in the stump or phantom, in this study the thermographic image could confirm the presence of phantom pain, but it could not rule out errors or false statements.     

Discovery of a new boron-containing antifungal agent, 5-fluoro-1,3-dihydro-1-hydroxy-2,1- benzoxaborole (AN2690), for the potential treatment of onychomycosis

A structure-activity relationship investigation for a more efficacious therapy to treat onychomycosis, a fungal infection of the toe and fingernails, led to the discovery of a boron-containing small molecule, 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2690), which is currently in clinical trials for onychomycosis topical treatment.     

Hypoplastische und keimepithelfreie Zonen in beidseits deszendierten Hoden als Zeichen einer partiellen Dysgenesie

Zusammenfassung Hypoplastische Zonen als Ausdruck einer partiellen Dysgenesie männlicher Keimdrüsen sind bisher erst in kryptorchen und pathologisch veränderten Hoden in ungefähr 50% der Fälle beschrieben worden. In einer Serie von 53 unausgewählten Sektionsfällen mit 105 makroskopisch normalen Scrotalhoden konnten hypoplastische Zonen ein einziges Mal=in 2 %, nämüch in beiden im übrigen postpuberal entwickelten Hoden eines 13jährigen Knaben histologisch nachgewiesen werden. Hypoplastische Zonen wurden später bei vier weiteren Fällen mit deszendierten Scrotalhoden gefunden. Es handelt sich um jüngere Leute im Alter von 17–26 Jahren. Die mikroskopische Untersuchung ergab zudem, da sich die hypoplastischen Zonen in Scrotalhoden unter dem Einflu der Entwicklungstendenz des scrotalen Milieus offenbar in keimepithelfreie Zonen weiterentwickeln können, wobei Übergangskanälchen als Zwischenstufen auftreten. Es kommen auch Übergänge von keimepithelfreien in normale Samenkanälchen vor. Derartige keimepithelfreie Zonen sprechen deshalb, wie die hypoplastischen Zonen, für eine partielle Dysgenesie. In einzelnen Fällen treten in keimepithelfreien Tubuli onkocytenartige Sertolizellen auf, die als Spermiophagen interpretiert werden. Die klinische Bedeutung der partiellen Dysgenesie beidseits deszendierter Hoden ist noch ungeklärt.

---

Summary Hypoplastic zones representative of partial dysgenesis have been described only in cryptorehid and pathologically altered testes in about 50% of the cases. In a series of 53 unselected autopsies with 105 macroscopically normal scrotal testes, hypoplastic zones could be demonstrated histologically in one instance (2%), namely, in both of the postpubertal testes of a 13 year old boy. In addition, in the descended scrotal testes of 4 young men between 17 and 26 years of age, hypoplastic zones could be found. The microscopic studies disclosed, that the hypoplastic zones in the scrotal testes could, under the influence of the developmental potentialities of the scrotal milieu, develop further into zones free of germinal cells, whereby the transitional seminiferous tubules appeared as intermediary stages. Transitions were found, from tubules free of germinal epithelium to normal tubules. The zones lacking germinal epithelium suggested, as did the hypoplastic zones, a partial dysgenesis. In a few cases oncocytic Sertoli cells appeared in the tubules free of germinal epithelium and these cells were interpreted as spermiophages. The clinical importance of partial dysgenesis in bilaterally descended testes remains unexplained.

     

Development of a thinner and more flexible type of minihysteroscope with a controlled 90-degree bendable tip for vision-guided endometrium biopsy

STUDY OBJECTIVE: Evaluation of the uterine cavity is limited with rigid 5-mm hysteroscopes because of the need for cervical dilatation, reduced movements inside the uterus, and no option for vision-guided biopsy. In cooperation with PolyDiagnost GmbH, Pfaffenhofen, Germany, a new type of flexible minihysteroscope with bendable tip was developed and evaluated. DESIGN: Prospective and parallel observational interindividual evaluation of flexible minihysteroscope and standard hysteroscope for diagnostic hysteroscopy (Canadian Task Force classification II-3). SETTING: Obstetrics and gynecology department of a university clinic. PATIENTS: Nine women, average age 65.0 years (range 46-89 years), with indications for diagnostic hysteroscopy. INTERVENTIONS: After defining requirements, a novel, thinner, and more flexible minihysteroscope, 18-cm long with a 2.67-mm outer diameter, was developed with straight zero-degree scope, 70-degree vision field, and 6000-pixel resolution. Two working channels, 1.2 mm and 0.55 mm, allow suction-irrigation and introduction of a 1.0-mm biopsy forceps or cytology brush. The tip of the instrument is 90-degree stageless bendable to both sides. Diagnostic hysteroscopy was performed with flexible minihysteroscope followed by standard rigid hysteroscopy to verify results. MEASUREMENTS AND MAIN RESULTS: From July 2003 through March 2004, both procedures were performed in nine patients with identical visual and histologic results. No complications occurred. No cervix-dilating instruments were necessary for introduction of the flexible minihysteroscope. Visualization of the entire uterine cavity is improved with the flexible scope because a bendable tip allows better peripheral vision (e.g., of the openings of the tubes). However, movement of the tip should be performed carefully due to potential risk of uterine perforation. CONCLUSION: This new flexible minihysteroscope is less invasive compared with standard rigid hysteroscopy, which supports performance of ambulatory hysteroscopy and makes increased movements and vision-guided biopsy inside the uterine cavity possible.     

Häufigkeit angeborener Störungen des Rot-Grün-Sinnes in Persisch-Aserbeidschan

Zusammenfassung 994 aserbeidschanische Schüler wurden am Anomaloskop geprüft. 4,5% zeigten Störungen des Rot-Grün-Sinnes. Die relative Häufigkeit der Deuteranomalen lag über, die der Protanopen unter dem europäischen Durchschnitt.     

Functional and histological changes after myoblast injections in the porcine rhabdosphincter

OBJECTIVE: Transurethral ultrasound-guided injection of autologous myoblasts has recently been shown to cure urinary stress incontinence. In the present study, the dose-dependent changes in maximal urethral closure pressures after application of myoblasts were investigated in a porcine animal model. METHODS: Myoblast cultures were grown from a porcine muscle biopsy. The biopsy was enzymatically dissociated by using a modified cell dispersion technique. Single myoblasts in suspension were manually collected with a micropipette under microscopic control. Next a clonal myoblast culture was prepared. Before the cells were applied, fluorescence labelling (PKH) was used to assess integration of the injected myoblasts into the rhabdosphincter. With the help of a transurethral ultrasound probe (23 F, 11 MHz) and a special injection system, the myoblasts were injected into the rhabdosphincter of five pigs under direct sonographic control. Into two different areas of the rhabdosphincter, increasing different cell counts were injected (total volume 1.5 ml). At each area, 10 depots of 150 microl volume were injected all along the rhabdosphincter. The following cell counts were used: 1.5 x 10(6), 2.1 x 10(6), 4.2 x 10(6) (low range) 5.69 x 10(6), 8.1 x 10(6), 1.13 x 10(7), 1.6 x 10(7) (mid range) 2.26 x 10(7), 4.4 x 10(7), and 7.8 x 10(7) (high range). To avoid possible cell rejection, we immunosuppressed the pigs with daily cortisone (1g Solu Dacortin) because allogenic myoblasts were used. Urethral pressure profiles (UPPs) were measured before and 3 wk postoperatively before the pigs were put to sleep. The lower urinary tract was removed in all pigs for histological analysis. RESULTS: Histological examination of the specimens revealed that the injected cells had survived at the injection site and had formed new myofibres. Overall the UPP curves revealed dose-dependent changes. Statistically significant increased pressure values of up to more than 300% could be observed in all cases in which higher concentrations of cells had been applied. Increases were also noted in mid range concentrations although not to such a high extent (approximately 150%). Pressure values had even diminished (approximately 50%) after injecting the three lowest concentrations (1.5 x 10(6), 2.1 x 10(6), 4.2 x 10(6)). CONCLUSIONS: The present results show that the effects after application of myoblasts into the rhabdosphincter are dose-dependent.