Highly sensitive high-performance liquid chromatographic-tandem mass spectrometric method for the analysis of dextromethorphan in human plasma.

A stable-isotope-dilution HPLC-tandem mass spectrometry-based method was developed for the determination of dextromethorphan in human plasma. Plasma samples were prepared for analysis by solid-phase extraction on octadecylsilane extraction cartridges. Dextromethorphan and the deuterium-labeled dextromethorphan internal standard were chromatographed on a short reversed-phase column and detected by a selected-reaction-monitoring scheme. Linear standard curves were obtained over three orders of magnitude and the limit of quantitation for dextromethorphan was 50 pg/ml, using a 1-ml plasma sample. The combination of HPLC and electrospray tandem mass spectrometry resulted in a rapid, selective and sensitive method for the analysis of dextromethorphan in plasma. The method was applied for the evaluation of the pharmacokinetic profile of dextromethorphan in human volunteers following peroral administration.

[The influence of consumer and direction on the quality of agricultural products and nutrition]. / Der Einfluss von Verbraucher und Handel auf die Qualität landwirtschaftlicher Produkte und Lebensmittel.

The modern consumer is very much interested in healthy food. The reason is that a special group of consumers is focusing more and more attention on health and nutrition problems. Further, there is increased emphasis on education in food science at universities as well as polytechnics. For some years worldwide dietary goals are published with the intention to reduce nutrition-based sickness. For the first time in our nutrition report 1988, clear proposals for optimal nutrition were formulated.

Anatomical study of the position of the mesial roots of mandibular molars.

In order to determine the position of the anatomical apex of the mesial roots of the first and second molars, the horizontal distance from the outer surface of the buccal cortical plate to the apex and the vertical distance from the superior border of the neurovascular bundle to the apex were examined in 33 human cadaver mandible halves. The vertical distances were compared with measurements taken from periapical radiographs between the apex of each mesial root and the superior border of the mandibular canal prior to sectioning. The means of the horizontal buccal distances of the second molar were found to be significantly greater than those of the first molar. The means of the vertical distances of the second molar were found to be significantly less than those of the first molar. A high correlation was found between the vertical anatomic and radiographic measurements. In the majority of the sections, the neurovascular bundle was found in the lingual half of the mandible.

Cutaneous papillomatous hyperplasia in cyclosporine-A treated beagles.

All twelve Beagle dogs undergoing long-term therapy (26 weeks) with the immunosuppressive drug cyclosporine-A (30 mg/kg), developed cutaneous papillomatous hyperplasia. By week 7 all dogs developed generalized lesions distributed over the entire body. These occurred as irregular, oval, sessile, unpigmented, firm masses. The incidence and severity of the skin lesions varied among dogs and anatomic site, with no correlation to the blood level of cyclosporine. Microscopic analysis revealed that the epidermis formed short papillary folds on broad fibrovascular stalks and was hyperkeratotic and acanthotic. Mild hyperplasia of hair follicles and sebaceous glands was also evident. A mild diffuse infiltrate of lymphocytes and plasma cells was present in the papillary dermis. No histopathologic changes typical of papillomavirus infection were identified, nor were papillomavirus group-specific antigens or viral DNA detected. Other cutaneous side effects included hyperkeratosis of footpads, increased growth of hair and nails, and hyperkeratinization of the haired skin of the prepuce. All cutaneous lesions regressed spontaneously within 8 weeks following termination of cyclosporine administration. The hyperplastic lesions may have resulted from the action of cyclosporine via the T-lymphocyte system. Conversely a direct action of this drug on epithelial cells may have stimulated proliferation and keratinization.

Cyclosporine-induced gingival overgrowth in beagle dogs.

Development of gingival overgrowth during daily long-term cyclosporine A treatment was studied in 2-yr-old beagles. Gingival enlargement developed in five of 12 dogs (42%), primarily in the mandibular anterior area. The earliest gingival changes occurred by 3 wk as an increase in the size of the interdental papillae. The lesions progressively became more severe, in some cases obscuring portions of teeth by wk 6. The redundant tissue exhibited an increase in connective tissue components and an inflammatory infiltrate primarily of plasma cells. Severity of the overgrowth varied in responding animals; both incidence and severity were related to the CSA concentration in blood. The mean CSA blood levels of responders were significantly greater than nonresponders at wk 3, 6 and 10. Since beagles develop gingival overgrowth similar to humans, they provide an excellent model to investigate the roles of local and systemic factors in the induction of gingival overgrowth.

[Protein quality of flatbread and extruded dry flatbread made from full-grain rye groats]. / Die Proteinqualität von Knäckebrot und extrudiertem Trockenflachbrot aus Roggenvollkornschrot.

The effect of various processing methods used for the production of dry flatbread from ground whole rye on the nutritional protein quality were investigated by means of the nitrogen balance method in growing rats. The following products were tested: untreated ground whole rye, baked crisp bread, extruded flatbread without and with the addition of 2.5% and 5.0% of saccharose. The apparent protein digestibility (PD) of the 5 samples varied between 69% and 72% and was neither affected by the method of processing nor by the difference in sugar content. Compared to the untreated raw material (NPU = 41%; BV = 59%) net protein utilization and biological value in crisp bread baked by the traditional method (NPU = 35%; BV = 48%) and in extruded flat bread with 5% sugar (NPU = 35%; BV = 51%) were significantly reduced (P less than 0.05). In extruded flatbread without and with 2.5% sugar, NPU and BV of the raw material were essentially maintained. The results indicate that in comparison with the baking process the extrusion of flatbread is more suitable to protect the protein quality. The addition of more than 2.5% sugar caused protein damage in extruded flatbread, presumably as a result of Maillard reactions.

[Effect of various extrusion conditions on the protein quality of soybean and whole rye meal]. / Der Einfluss verschiedener Extrusionsbedingungen auf die Proteinqualität von Sojaschrot und Roggenvollkornschrot.

Using a Creusot-Loire twin-screw extruder (Type BC 45), ground soy bean and whole rye meal were extruded under various processing conditions (12% and 18% water content in the raw material, 129 degrees C and 165 degrees C product temperature in the case of soy bean, 12% and 18% water content, 165 degrees C product temperature in the case of rye, screw speed of 150 R/min, for all samples). The nutritional protein quality (apparent protein digestibility PV, net protein utilization NPU, and biological value BW) of the extrudates was determined by the nitrogen balance technique in growing rats. Compared to the untreated raw material no decrease in PV or NPU was noted for extrudates made from soy bean or rye. Extrusion of ground soy bean at 165 degrees C and 18% water content caused a significant decrease of BW from 68% to 64%. The lower water content (12%) induced a slight improvement of PV in soy extrudates and of NPU and BW in rye extrudates. The results indicate that the extrusion at low water content and moderate temperature can safely be used to process ground soy bean and whole rye meal without and damage to the nutritional protein quality.

[Bacteriological findings in conjunctival smears]. / Bakteriologische Befunde in Bindehautabstrichen.

Between February and December 1981 a total of 2,053 conjunctival smears were taken on chocolate agar plates. Of these specimens, 1,720 were taken from clear, noninflamed eyes on the day preceding intraocular surgery; 202 (11.7%) of the smears were positive. The most common pathogens were gram-positive cocci (119 X) and Staphylococcus aureus (47 X). In 333 cases the smears were taken from the anterior segments of eyes with manifest infection and inflammatory signs. In this group pathogens grew on 95 smears (26%), the most common being gram-positive cocci (92 X) and Staphylococcus aureus (32 X). As more than one pathogen grew in 80 of the 95 smear cultures, a total of 174 pathogens were found in this group.

Growth pattern and citrate production in organ cultures of adult rat ventral prostate.

Prostate rudiments from Wistar rats were cultured in MEM supplemented with 15% FBS and insulin (2 microgram/ml). In situ prostate acinar epithelium consists of tall columnar and low basal cells. Ultrastructure of the columnar cells is that of typical secretory cells; however, the basal cells are poor in cell organelle. During the first week of culture many secretory cells degenerated and were replaced by cuboidal or low columnar cells. In the presence of testosterone (2 microgram/ml) the secretory cells remained viable for 8-10 days before undergoing necrosis. At the termination of the experiment the acinar epithelium consisted of low cuboidal cells. The cultures showed a pattern of citrate production which reached a maximum at 5 days and remained-relatively constant thereafter. Ultrastructure of 1-week cultures exhibited Golgi complexes with dilated cisternae. Although a paucity of cell organelle was found in 7-day cultures, older cultures (19 days) exhibited morphologic characteristics of normal secretory cells.

The effects of nicotine on mouse first molar tooth germs in organ culture.

Mandibular first molars, extirpated from 18-day mouse fetuses were cultured in BGJb medium (Fitton-Jackson modification) in a Trowell type culture system. Two-day cultures were treated with 78, 117, 156, and 312 microgram/ml nicotine sulfate. Untreated control tooth germs demonstrated normal growth in vitro. The peripheral cell layer of mesenchymal papilla and the inner enamel epithelium differentiated into odontoblasts and ameloblasts respectively with subsequent elaboration of extracellular matrix. Tooth germs treated with 78 microgram/ml nicotine were only slightly affected where as higher doses of the drug produced extensive cell damage. Dental papilla appeared more sensitive than the enamel organ. Large necrotic foci were present in the pulp mesenchyme involving in some cases the odontogenic layer and severely limiting production of predentin. The basement membrane in these areas was partially disrupted and stained poorly for PAS. The inner enamel epithelium was not affected by 78 microgram/ml dose of nicotine, however, higher doses produced extensive cell necrosis in this layer. Although enamel matrix was abundantly present in untreated controls, the tooth germs exposed to 117, 156, and 312 microgram/ml nicotine sulfate failed to elaborate this extracellular matrix. Tooth germs exposed to nicotine for 24 hours followed by culturing in control medium demonstrated complete recovery. Treated cultures maintained in vitro for 7-9 days in control media had replaced the necrotic cells in the ameloblastic and odontoblastic layers and demonstrated abundant dentin and enamel matrices.

Ultrastructural localization of adenosine triphosphatase in the stellate reticulum, stratum intermedium and ameloblasts of the mouse molar.

ATPase activity in the developing first mandibular molar of the mouse was demonstrated at the electron microscopic level with the method of Wachstein & Meisel (1957). It was localized along the cell surfaces of the ameloblast and stratum intermedium interface, the stratum intermedium and the stellate reticulum. The ATPase final reaction product was also present at the cell membranes of the proximal region of adjacent ameloblasts and extended to the level of the nuclei. The demonstration of ATPase mainly on the plasma membranes was similar to the observations by other investigators of various non-odontogenic cell types involved in the exchange of materials across plasma membranes.

A fine-structural analysis of mouse molar odontoblast maturation.

The first mandibular molars of the Swiss albino mice, 1 through 4 days of age, were fixed in glutaraldehyde or Karnovsky's fixative. The tissues were postfixed in OSO4, dehydrated and embedded in Epon. The prepolarizing, polarizing and secretory odontoblasts were described. The prepolarizing cells, located in the vicinity of the cervical loop, were mesenchymal-like in morphology. The cells of the polarizing stage possessed organelles indicative of protein synthesis. The nucleus was located proximally. Aperiodic fibers were evident in the wide basement membrane. The secretory odontoblasts were long, slender, polarized cells closely adjoining one another. Each odontoblast possessed six morphologically discernible regions: (1) an infranuclear region, limited in size and containing few cellular organelles; (2) a nuclear region, housing the oval nucleus and a few associated lamellae of rough endoplasmic reticulum as well as a limited number of mitochondria; (3) a supranuclear rough endoplasmic reticulum region, possessing an abundance of these organelles as well as some mitochondria and secretory vesicles; (4) a Golgi region, occupying the middle third of the cell, housing the elements of an extensive Golgi apparatus which was surrounded by peripherally located profiles of rough endoplasmic reticulum; additionally, this region contained smooth endoplasmic reticulum, mitochondria, numerous secretory granules and vesicles and occasional intracellular collagen fibers; (5) an apical rough endoplasmic reticulum region, containing a rough endoplasmic reticulum component that was less extensive than its supranuclear counterpart; in addition, this region was the one richest in mitochondria and contained a plethora of secretory vesicles and granules; (6) the odontoblastic process, a region mostly void of organelles, containing various secretory products, some of which appeared to be in the process of being released extracellularly into the surrounding dentin matrix.

Electron microscopic localization of 5'-nucleotidase in the stratum intermedium and ameloblasts.

5'-nucleotidase was demonstrated at the fine structural level in the stratum intermedium and ameloblasts of the first mandibular molars of CD-1 mice. The enzyme was localized with the Wachstein & Meisel (1957) method along the plasma membranes of the cells of the stratum intermedium and ameloblasts. While 5'- nucleotidase was present throughout the stratum intermedium, only the proximal region of the plasma membranes of ameloblasts was demonstrably active for this enzyme. 5'-Nucleotidase has been implicated in transport of metabolites across cell membranes, and its localization in the present study supports this implication as well as the transport functions of the stratum intermedium and the stratum intermedium--ameloblastic interface.