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Ectopic p16(ink4) expression enhances CPT-11-induced apoptosis through increased delay in S-phase progression in human non-small-cell-lung-cancer cells.

A tumor-suppressor gene, p16(INK4), which is deleted or mutated in tumors, regulates cell-cycle progression through a G(1)-S restriction point by inhibiting CDK4(CDK6)/cyclin-D-mediated phosphorylation of pRb. We have found that ectopic p16(INK4) expression increased cellular sensitivity of human non-small-cell-lung-cancer (NSCLC) A549 cells to a selective growth-inhibitory effect induced by the topoisomerase-I inhibitor 11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy camptothecin (CPT-11) in vitro. In this study, we observed enhanced apoptosis characterized by DNA fragmentation in A549 cells transfected with p16(INK4) cDNA (A549/p16-1) and treated with CPT-11. This apoptosis was suppressed by the inhibitor of interleukin-1beta-converting enzyme (ICE/caspase-1) or ICE-like proteases, Z-Asp-CH2-DCB, as determined by DNA fragmentation and proteolytic cleavage of poly(ADP-ribose) polymerase, a natural substrate for CPP32/caspase-3. In A549/p16-1 cells, cytosolic peptidase activities that cleaved Z-DEVD-7-amino-4-trifluoromethylcoumarin increased during CPT-11-induced apoptosis and were suppressed by a highly specific caspase-3 and caspase-3-like inhibitor, Z-DEVD-fluoromethylketone. These findings indicate that p16(INK) is positively involved in the activation pathway of the caspase-3 induced by CPT-11. The increased delay in S-phase progression and subsequent induction of apoptosis were observed in CPT-11-treated A549/p16-1 cells on the basis of DNA histograms. Specific down-regulation of the cyclin-A protein level in A549/p16-1 cells was observed after CPT-11-treatment, whereas cyclin B, cdk2, and cdc2 protein levels were unaffected. These results suggest that ectopic p16(INK4) expression inappropriately decreases cyclin A and thereby terminates CPT-11-induced G(2)/M accumulation, which is followed by increased apoptosis in p16(INK4)-expressing A549 cells.

Antineoplastic Agents, Phytogenic↗

Pancreatic microcirculation in the monkey with special reference to the blood drainage system of Langerhans islets: light and scanning electron microscopic study.

The microcirculation of the pancreas in 20 monkeys (Macaca mulatta) was further studied by scanning electron microscopy (SEM) of vascular corrosion casts and light microscopy (LM) of Chinese ink-injected/cleared tissues. The results revealed that 91% of islets observed received arterial blood from the terminal branches of the intralobular arteries--the afferent arterioles, and 9% received no arterial blood, being entirely supplied by the efferent vessels of the intermediate or large islets. Some islets received blood from the translobular afferent arterioles of the adjacent lobule. Two patterns of islet drainage channels with different features in the monkey were demonstrated in our study. These patterns might be termed as continuous or convergent portal vessels. All islets possessed continuous portal vessels, 7-8 microns in diameter, which ran a short distance (approximately 100 microns) and then drained into the peri-islet acinar region, forming a typical continuous insulo-acinar portal system. About 21% of the islets possessed one or two convergent portal vessels, occasionally more. This was first observed in the monkey. These vessels were relatively long and/or thick and drained into different regions: (1) the acinar region far from the islet in the lobule, forming a convergent insulo-acinar portal system, (2) crossed the interlobular septum into an adjacent lobule where sometimes no islet existed and then drained into the exocrine acinar region, forming a translobar convergent insulo-acinar portal system, (3) drained into an adjacent small islet through the insulo-insular drainage vessels--one part of the drainage system of the islets. Translobular vascular anastomoses observed between the microcirculation of pancreatic lobules in the monkey formed a new arrangement of pancreatic microcirculation-translobular pancreatic microcirculation. The functional and clinical significance of the pancreatic portal circulation and translobular circulation is discussed in this report.

Animals↗

Neovascularized bone grafts: experimental investigation.

Vascularized bone grafts are standardized procedures in reconstructive surgery but there are some disadvantages: donor site morbidity, limited number of "natural" donor sites, and complex technique. In this study, we test the possibility of creating a "neovascularized" bone graft utilizing a vascular implantation procedure in a rabbit model. Sixteen New Zealand adult white rabbits were used. In each animal, two iliac crest bone grafts (7 x 7 x 10 mm) were harvested. Vascular implantation of the right superficial femoral vessels was performed in one of the two grafts, which was wrapped in a silicone envelope to avoid neovascularization from the surrounding tissues and positioned in a subcutaneous pocket in the right medial thigh. On the left side, the bone block, wrapped in the silicone envelope, was buried subcutaneously without vascular implantation. The operated animals were divided into two groups: Group I included eight rabbits explanted 4 weeks postoperatively and Group II included eight rabbits explanted 8 weeks postoperatively. Tetracycline injection was performed 72 hours preexplantation to evaluate new bone formation. Selective colloidal ink injection in the axial artery was performed to investigate the neovascularization before inclusion in poly-methyl-methacrylate (PMMA). Histological examination was performed in all explanted specimens comparatively. Histological examination 8 weeks after surgery showed a marked neovascularization, with normal bone cells. Tetracycline labeling showed new bone formation with a normal pattern. In all nonvascularized specimens, no viable cells or neovascularization and no bone formation were found. The vascular implantation procedure can induce a good neovascularization with new bone formation in a small bone graft. The possibility of neovascularization induction by the simple vascular implantation procedure has several clinical implications in reconstructive surgery.

Animals↗

DNA damage in isolated rat hepatocytes exposed to C.I. pigment orange 5 and C.I. pigment yellow 12 by the alkaline comet assay.

The induction of DNA damage by commonly used printing ink pigments, C.I. pigment orange 5 (C.I. 12075) and C.I. pigment yellow 12 (C.I. 21090), was investigated in freshly isolated rat hepatocytes with the comet assay. C.I. pigment yellow 12 is a 3,3'-dichlorobenzidine-based diarylide pigment, and C.I. pigment orange 5 is a naphthol-azo pigment. The pigments are virtually insoluble in aqueous solutions, and they have not been tested extensively for toxicological effects. C.I. pigment orange 5 increased the levels of DNA damage at 5 microg/ml (P < 0.02) and C.I. pigment yellow 12 at 20 microg/ml (P < 0.002). The effect of incubation time (20, 40, and 80 min) of the same concentrations of the pigments was tested. The levels of DNA damage were increased up to 80 min. Both pigments produced DNA damage that was in the same range as the food carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline. Our data indicate that both C.I. pigment orange 5 and C.I. pigment yellow 12 are genotoxic in hepatocytes with metabolizing capacities. However, further investigation of the metabolism and disposition are required for the evaluation of the safety of these pigments.

Alkalies↗

Laser skin welding: in vivo tensile strength and wound healing results.

BACKGROUND AND OBJECTIVE: Laser skin welding was investigated as a general model for laser tissue closure. Scanned delivery of near-infrared laser radiation in combination with a dye can produce strong welds with limited thermal damage. STUDY DESIGN/MATERIALS AND METHODS: Two-centimeter-long, full-thickness incisions were made on the backs of guinea pigs. Wounds were closed either by laser welding or sutures and then biopsied at 0, 3, 6, 10, 14, 21, and 28 days postoperatively. Welding was achieved by using continuous-wave, 1. 06-micrometer, Nd:YAG laser radiation scanned over the incisions to produce a dwell time of approximately 80 msec. The cooling time between scans was fixed at 8 seconds. A 4-mm-diameter laser spot was maintained during the experiments, and the power was kept constant at 10 W. The operation time was fixed at 10 minutes per incision. India ink was used as an absorber of the laser radiation at the weld site, and clamps were used temporarily to appose the incision edges. RESULTS: Acute weld strengths of 2.1 +/- 0.7 kg/cm(2) were significantly higher than suture apposition strengths of 0.4 +/- 0.1 kg/cm(2) (P < 0.01), and weld strengths continued to increase over time. Lateral thermal damage in the laser welds was limited to 200 +/- 40 micrometer near the epidermal surface with less thermal damage deeper within the dermis. CONCLUSION: Our welding technique produced higher weld strengths and less thermal damage than reported in previous skin welding studies and may represent an alternative to sutures.

Animals↗

Successful treatment of treatment-resistant laser-induced pigment darkening of a cosmetic tattoo.

BACKGROUND AND OBJECTIVE: Cosmetic tattoo removal has a reported risk of immediate pigment darkening when treated with a high energy, nanosecond pulsed-laser system. Surgical treatment options for this reaction are limited and carry significant risk of scarring and permanent pigment alterations. This report describes the response of a resistant Q-switched ruby laser-induced cosmetic tattoo ink darkening to multiple treatments with the Q-switched alexandrite laser and Q-switch Nd:YAG laser and textural improvement with the UltraPulse CO(2) laser. STUDY DESIGN/MATERIALS AND METHODS: A woman with Q-switched ruby laser-induced pigment darkening of a cosmetic tattoo of the upper lip resistant to four further treatments with the ruby laser and two chemical peels received a total of 26 treatments with the Q-switched alexandrite and Nd:YAG lasers and a single treatment with the UltraPulse CO(2) laser, most treatments being done at monthly intervals. RESULTS: Treatment of the affected areas with the Q-switched alexandrite and Nd:YAG lasers resulted in complete clearing of the pigment without scarring, but revealed some preexisting textural changes. Use of the UltraPulse CO(2) laser smoothed the surface irregularities. CONCLUSION: The Q-switched pigment lasers are a useful modality for treating this pigment darkening reaction. As in this case, multiple treatment sessions with the laser may be necessary but the pigment can be expected to clear eventually without scarring. Any textural changes may be blended with the UltraPulse CO(2) laser with further improvement.

Adult↗

Occupation and risk of uveal melanoma. An exploratory study.

BACKGROUND: Little is known about the cause of uveal melanoma, the most common primary intraocular malignant lesion in adults. This population-based case-control study evaluated occupational exposures. METHODS: One hundred ninety-seven newly diagnosed cases of uveal melanoma participated. Approximately two control subjects matched for age, sex, and telephone exchange area were selected for each case by random-digit dialing. Data were collected by a structured telephone interview. Two systems of occupational coding were used: an occupation-exposure linkage system and the Bureau of Census data. Conditional logistic regression for matched studies was used to examine various occupational exposures while controlling for previously reported potential confounders and for family income. The occupation-exposure matrix was used to define clusters of cases exposed to a particular chemical group from various occupations. RESULTS: Odds ratios were elevated for agriculture and farming work for both industry and occupation; this was consistent across both classification systems. Elevated odds ratios also were found for occupations involving machine operations, fabrication, assembling, equipment cleaning, and exposure to metal industries. Exposure to alkylating agents and phenols was associated with a lower risk compared with all other exposures. Several self-reported exposures also were studied. Exposures associated with elevated odds ratios were inks, insecticides, gases, radioactive substances, polybromated biphenyls, and chemical solvents. CONCLUSIONS: This exploratory study suggests various occupational associations for uveal melanoma and areas for future research.

Adolescent↗

Can intraductal breast carcinoma be excised completely by local excision? Clinical and pathologic predictors.

BACKGROUND: Microscopic evaluation of excised intraductal breast carcinoma (DCIS) specimens using a serial subgross technique reveals that in many patients the lesion is larger than expected, often making complete excision impossible with less than a true quadrantectomy. Data is presented on 181 patients with DCIS in whom the initial biopsy was performed using a more cosmetic wide local excision rather than a true quadrantectomy. METHODS: Clear margins were defined as no tumor within 1 mm of any inked or dyed margin. All of these patients subsequently underwent mastectomy or reexcision of the initial biopsy site. This allowed pathologic evaluation for residual disease. RESULTS: At mastectomy or reexcision, 76% of patients with initially involved margins had residual DCIS, as did 43% of patients with initially clear margins (P < 0.0001). Larger tumor size was a statistically significant predictor of initial margin involvement and residual DCIS (P < 0.05). Patients with comedo-DCIS had a greater tendency toward positive initial histologic margins and residual DCIS, but this trend was not statistically significant (P < 0.1). CONCLUSION: DCIS presents major problems to both surgeons and pathologists. It is difficult to excise completely using a wide local excision. Histologically negative margins do not guarantee that residual DCIS has not been left behind. Inadequate excision of the primary lesions may be the most important cause of local failure after conservative treatment for intraductal breast carcinoma.

Biopsy↗

The importance of the lumpectomy surgical margin status in long-term results of breast conservation.

BACKGROUND: The impact of the surgical margin status on long-term local control rates for breast cancer in women treated with lumpectomy and radiation therapy is unclear. METHODS: The records of 289 women with 303 invasive breast cancers who were treated with lumpectomy and radiation therapy from 1972 to 1992 were reviewed. The surgical margin was classified as positive (transecting the inked margin), close (less than or equal to 2 mm from the margin), negative, or indeterminate, based on the initial biopsy findings and reexcision specimens, as appropriate. Various clinical and pathologic factors were analyzed as potential prognostic factors for local recurrence in addition to the margin status, including T classification, N classification, age, histologic features, and use of adjuvant therapy. The mean follow-up was 6.25 years. RESULTS: The actuarial probability of freedom from local recurrence for the entire group of patients at 5 and 10 years was 94% and 87%, respectively. The actuarial probability of local control at 10 years was 98% for those patients with negative surgical margins versus 82% for all others (P = 0.007). The local control rate at 10 years was 97% for patients who underwent reexcision and 84% for those who did not. Reexcision appears to convey a local control benefit for those patients with close, indeterminate, or positive initial margins, when negative final margins are attained (P = 0.0001). Final margin status was the most significant determinant of local recurrence rates in univariate analysis. By multivariate analysis, the final margin status and use of adjuvant chemotherapy were significant prognostic factors. CONCLUSIONS: The attainment of negative surgical margins, initially or at the time of reexcision, is the most significant predictor of local control after breast-conserving treatment with lumpectomy and radiation therapy.

Adult↗

Carbon dye histologically confirms the identity of sentinel lymph nodes in cutaneous melanoma.

BACKGROUND: False-negative results from lymphatic mapping and sentinel lymphadenectomy (LM/SL) are associated with technical failures in nuclear medicine and surgery or with erroneous histologic evaluation. Any method that can confirm sentinel lymph node (SN) identity might decrease the false-negative rate. Carbon dye has been used as an adjunct to assist lymphadenectomy for some tumors, and the authors hypothesized that it could be used for the histologic verification of SNs removed during LM/SL. The current study assessed the clinical utility of carbon dye as a histopathologic adjunct for the identification of SNs in patients with melanoma and correlated the presence of carbon particles with the histopathologic status of the SNs. METHODS: LM/SL was performed using carbon dye (India ink) combined with isosulfan blue dye and sulfur colloid. Blue-stained and/or radioactive lymph nodes (two times background) were defined as SNs. Lymph nodes were evaluated for the presence of carbon particles and melanoma cells. If an SN lacked carbon dye in the initial histologic sections, four additional levels were obtained with S-100 protein and HMB-45 immunohistochemistry. Completion lymph node dissection (CLND) was performed if any SN contained melanoma cells. RESULTS: One hundred patients underwent successful LM/SL in 120 lymph node regions. Carbon particles were identified in 199 SNs from 111 lymph node regions of 96 patients. Sixteen patients had tumor-positive SNs, all of which contained carbon particles. The anatomic location of the carbon particles within these tumor-positive SNs was found to be correlated with the location of tumor cells in the SNs. The presence of carbon particles appeared to be correlated with blue-black staining (P = 0.0001) and with tumor foci (P = 0.028). All 35 non-SNs that were removed during LM/SL were tumor-negative, and only 2 contained carbon particles. Of the 272 non-SNs removed during CLND, 5 contained metastases; 3 of these 5 were the only non-SNs that had carbon particles. The use of carbon particles during LM/SL was found to be safe and nontoxic. CONCLUSIONS: Carbon dye used in LM/SL for melanoma permits the histologic confirmation of SNs. Carbon particles facilitate histologic evaluation by directing the pathologist to the SNs most likely to contain tumor. The location of carbon particles within SNs may assist the pathologist in the detection of metastases, thereby decreasing the histopathologic false-negative rate of LM/SL and subsequently reducing the same-basin recurrence rate.

Adult↗

Neurovascular plasticity in the knee joint of an arthritic mouse model.

Lower numbers of neuropeptide-containing fibers in arthritic joints have been found as compared to control joints. This may be the result of fiber depletion, necrosis of fibers, or proliferation of soft tissues without neural sprouting. To discriminate between these possibilities, we studied the relationships between soft tissue proliferation, changes in vascularity of synovial tissues, and changes in joint innervation during arthritis. Arthritis was induced in the knee joint of mice by a single subpatellar injection of methylated bovine serum albumin after previous immunization. Antibodies to protein gene product 9.5, S-100, and growth-associated protein-43 (GAP-43) were used to study the general innervation pattern. Antibodies to calcitonin gene-related peptide (CGRP), vasointestinal polypeptide (VIP), substance P (SP), and tyrosine hydroxylase (TH) were used to localize sensory (SP, CGRP, VIP) and sympathetic (TH) fibers. Blood vessels of the joint were studied with ink perfusion, GAP-43, and a vascular marker (LF1). Directly after the induction of arthritis, the synovial cavity was enlarged and filled with leukocytes. From day 4 onward, small sprouting blood vessels penetrated the avascular mass of cells in the joint cavity. After 1 week, the vascular sprouting activity and GAP-43 immunoreactivity were maximal, and after 2 weeks, vascular sprouting activity diminished. In the subsequent period, the synovia slowly regained their prearthritic appearance and thickness. The most pronounced changes in the general staining pattern of CGRP, SP, VIP, and TH were found in the periosteum. From 2 days to 4 weeks after the induction of arthritis, the layer of SP, CGRP, and VIP fibers in the femoral periosteum was thicker and more irregular. GAP-43 staining showed many terminal varicosities, which suggested sprouting of nerve fibers. From 2 days to 2 weeks after the induction of arthritis, the SP and CGRP fibers in the periosteum showed gradual depletion. In the thickened subsynovial tissues that were revascularized, no ingrowth of neural elements was found. As the total number of nerve fibers in the synovial tissue did not change, large parts of the synovia directly facing the joint cavity were not innervated at 1 week after the induction of arthritis. These results strongly suggest that periosteal SP and CGRP fibers were depleted during arthritis. Synovial proliferation without concomitant fiber growth is the main cause of the reduced number of immunocytochemically detectable fibers in the mouse arthritic knee joint.

Animals↗

Occupational risk factors for renal cell carcinoma in Montreal.

BACKGROUND: Little is known about the role of workplace exposures on the risk of renal cell cancer. METHODS: A population-based case-control study was undertaken in Montreal to assess the association between hundreds of occupational circumstances and several cancer sites, including the kidney. A total of 142 male patients with pathologically confirmed renal cell carcinoma, 1900 controls with cancer at other sites and 533 population-based controls were interviewed. Detailed job histories and relevant data on potential confounders were obtained. A group of chemists-hygienists evaluated each job reported and translated them into a history of occupational exposures using a checklist of 294 substances. Multivariate logistic regression models using either population, cancer controls, or a pool of both groups were used to estimate odds ratios. RESULTS: There were some indications of excess risks among printers, nursery workers (gardening), aircraft mechanics, farmers, and horticulturists, as well as in the following industries: printing-related services, defense services, wholesale trade, and retail trade. Notwithstanding the low precision of many of the odds ratio estimates, the following workplace exposures showed some evidence of excess risk: chromium compounds, chromium (VI) compounds, inorganic acid solutions, styrene-butadiene rubber, ozone, hydrogen sulphide, ultraviolet radiation, hair dust, felt dust, jet fuel engine emissions, jet fuel, aviation gasoline, phosphoric acid and inks. CONCLUSIONS: For most of these associations there exist no, or very little, previous data. Some associations provide suggestive evidence for further studies.

Adult↗

A cohort mortality study of U.K. carbon black workers, 1951-1996.

BACKGROUND: Carbon black, a powdered form of elemental carbon is used in the manufacture of rubber products, paints, plastics, and inks. In 1974, the Health and Safety Executive initiated a cohort mortality study on possible carcinogenic effects on carbon black workers. METHODS: The mortality of a cohort of 1,147 male manual workers from five U.K. factories manufacturing carbon black was investigated for the period 1951-1996. All subjects were employed in the carbon black industry for 12 months or more, and all were first employed before 1975. Limited work histories were used to calculate estimates of individual cumulative exposure to carbon black, using a job-exposure matrix derived by the study team. RESULTS: Based on serial rates for the general population of England and Wales, significantly elevated mortality was observed in the main study cohort for all causes (Obs 372, Exp 328.7, SMR 113, P < 0.05) and for lung cancer (Obs 61, Exp 35.3, SMR 173, P < 0.001). There were highly elevated lung cancer SMRs at two of the factories, and unexceptional SMRs at the remaining three factories. There was no indication of lung cancer SMRs increasing with period from first employment. Poisson regression analyses failed to find significant trends of lung cancer risks increasing either with cumulative exposure to carbon black (4 levels) or with duration of employment at the participating factories (4 levels). CONCLUSIONS: Confident interpretation of the elevated SMRs found for lung cancer in two of the factory subcohorts is not possible but the study has been unable to link cumulative exposure to carbon black with elevated risks of lung cancer.

Adult↗

Design and fabrication of cast orthopedic implants with freeform surface textures from 3-D printed ceramic shell.

Three-dimensional printing is a solid freeform fabrication process, which creates parts directly from a computer model. The parts are built by repetitively spreading a layer of powder and selectively joining the powder in the layer by ink-jet printing of a binder material. 3D printing was applied to the fabrication of sub-millimeter surface textures with overhang and undercut geometries for use in orthopedic prostheses as bony ingrowth structures. 3D printing is used to fabricate ceramic molds of alumina powder and silica binder, and these molds are used to cast the bony ingrowth surfaces of Co-Cr (ASTM F75) alloy. Minimum positive feature sizes of the ceramic mold and, therefore, minimum negative feature sizes of castings were determined to be approximately 200 x 200 x 175 microm and were limited by the strength of ceramic needed to withstand handling. Minimum negative feature sizes in the ceramic mold and, therefore, minimum positive features in the casting were found to be approximately 350 x 350 x 175 microm and were determined by limitations on removal of powder from the ceramic and the pressure required to fill these small features with molten metal during casting. Textures were designed with 5 layers of distinct geometric definition, allowing for the design of overhung geometry with overall porosity ranging from 30-70%. Features as small as 350 x 350 x 200 microm were included in these designs and successfully cast.

Ceramics↗

Rorschach predictors of therapeutic outcome for inpatient treatment of children: a proactive study.

The present study tested the hypothesis that Rorschach measures of psychological instability and perceptual sensitivity (i.e., es, es-EA, Lambda, Blends, Zf, & Zsum) would be sensitive to therapeutic change after inpatient treatment of children. Twelve male children were administered the Rorschach Ink Blot test in accordance with Exner's (1986) procedures and comprehensive system, pretreatment and posttreatment. The 12 children received inpatient treatment an average of 12 months, and all children showed improved functioning after treatment. Pre- to posttreatment Rorschach performance changes provided a partial confirmation of the hypothesis. Specifically, significant changes in es and Lambda were found posttreatment. As such, these Rorschach variables appear to be sensitive to therapeutic change in children.

Adolescent↗

Anatomy and clinical significance of ventricular Thebesian veins.

An injection study was carried out in sheep hearts to compare the anatomy and distribution of Thebesian veins (venae cordis minimae) in the ventricles. The left azygos, middle cardiac, small cardiac, and anterior cardiac veins were ligated in 36 hearts, and India ink was injected into the right coronary artery or the left coronary artery or the coronary sinus. Examination revealed foramina Thebesii in both of these cardiac chambers. Myocardial tissue samples were taken, and 12 were subsequently studied histologically to confirm the presence of Thebesian veins. A greater number of Thebesian veins were observed in the right ventricle than in the left (P < 0.05). To identify any larger communications between the coronary arteries and cardiac chambers (arterioluminal), and between the coronary veins and cardiac chambers (venoluminal), gelatine was injected in 16 hearts. Arterioluminal vessels were identified only in the right ventricle, whereas venoluminal vessels were present in both ventricles. Venoluminal vessels are most likely responsible for the non-nutritive shunting of cardioplegic solutions delivered via the coronary sinus during surgery. Thebesian veins play a role in the drainage of blood, contributing towards right to left shunting of deoxygenated blood. It has also been suggested, although not proven, that they are able to supply blood to the myocardium in coronary arterial occlusion, thus acting as a natural form of nutrient channel. Thebesian veins may be confused with artificial nutrient channels constructed by transmyocardial laser revascularization, a possibility that should be considered during histological evaluation of this technique.

Animals↗

Organic Nanoparticles in the Aqueous Phase-Theory, Experiment, and Use.

Many active organic compounds and organic effect materials are poorly soluble in water, or even insoluble. Aqueous forms of application thus require special formulation techniques to utilize or optimize the physiological (pharmaceuticals, cosmetics, plant protection, nutrition) or technical (varnishes, printing inks, toners) action. The most interesting properties of nanodispersions of active organic compounds and effect materials include the impressive increase in solubility, the improvement in biological resorption, and the modification of optical, electrooptical, and other physical properties which are achievable only with particle sizes in the middle or lower nanometer range (50-500 nm). Hence in addition to economic and ecological constraints there are also technical demands which appear to urgently require the development of new processes for the production of organic nanoparticles as alternatives to the established mechanical milling processes. In this context attention is drawn to the recent increase in research activities which have as their objective the continuous, automatic preparation of nanodispersed systems by precipitation from molecular solution. In this review the current state of knowledge of the fundamentals of particle formation from homogeneous solution and the effect of solvent and polymer additives on the morphology and supramolecular structure of the nanoparticle will be discussed. The practical implementation of this new formulation technology will be explored in detail for the carotenoids, a class of compounds of both physiological and technical interest.

Journal Article↗

Advances ofcapillary electrophoresis in clinical and forensic analysis (1999-2000).

In this paper, capillary electrophoresis in clinical and forensic analysis is reviewed on the basis of the literature of 1999, 2000 and the first papers in 2001. An overview of progress relevant examples for each major field of application, namely (i) analysis of drug seizures, explosives residues, gunshot residues and inks, (ii) monitoring of drugs, endogenous small molecules and ions in biofluids and tissues, (iii) general screening for serum proteins and analysis of specific proteins (carbohydrate deficient transferrin, alpha1-antitrypsin, lipoproteins and hemoglobins) in biological fluids, and (iv) analysis of nucleic acids and oligonucleotides in biological samples, including oligonucleotide therapeutics, are presented.

Clinical Chemistry Tests↗