Minimal Morphological Changes Research Articles

Effects of antifungal drugs and delivery vehicles on morphology and proliferation of equine corneal keratocytes in vitro

To evaluate the effects of topical antifungal drugs and delivery vehicles on the morphology and proliferation rate of cultured equine keratocytes. 16 corneas obtained from 8 apparently ophthalmologically normal horses < 0.5 hours after euthanasia for reasons unrelated to the study. Primary cultures of equine keratocytes were obtained from corneal stroma and were exposed to several concentrations of 3 commonly used, topically applied antifungals: natamycin, itraconazole, and miconazole. In addition, effects of drug delivery vehicles DMSO, benzalkonium chloride, and carboxymethylcellulose and a combination vehicle composed of polyethylene glycol, methylparaben, and propylparaben were also evaluated. Morphological changes and cellular proliferation were assessed 24, 48, and 72 hours after application. At the highest concentrations tested, all antifungals caused marked cellular morphological changes and inhibited proliferation. At low concentrations, natamycin and miconazole induced rounding, shrinking, and detaching of the cells with inhibition of cellular proliferation. Natamycin caused the most severe cellular changes. Itraconazole, at the low concentrations, caused minimal morphological changes and had a minimal effect on proliferation. All vehicles tested had significantly less effects on cellular morphology and proliferation when compared with the antifungals, except for the combination vehicle, which caused severe morphological changes and inhibited proliferation, even at low concentrations. The DMSO had minimal effects on cellular morphology and proliferation, even at high concentrations. Itraconazole had significantly less cytotoxic effects on equine keratocytes in culture than did natamycin or miconazole. Natamycin had severe cytotoxic effects in vitro.

Histopathological findings after treatment of prostate cancer using high‐intensity focused ultrasound (HIFU)

High-intensity focused ultrasound (HIFU) treatment is a novel minimally invasive therapeutic option for patients with localized prostate cancer. Little is known about the histological findings in prostate biopsies upon HIFU treatment. We examined the spectrum of histological changes in prostate biopsies of 25 prostate cancer patients who were previously treated with HIFU. The biopsies were taken 180 days after HIFU treatment. Seventy-two percent of the cases showed necrosis, often accompanied by acute, chronic, or granulomatous inflammation. Mild or moderate fibrosis was present in all biopsies. In benign glands, histological examination revealed a heterogeneous cellular damage and cellular response including cytologic atypia and basal cell hyperplasia. Eleven patients (44%) had residual prostatic carcinoma after treatment. In cases with residual adenocarcinoma, the majority of the cases (9/11, 88%) do no have apparent treatment effects. Two cases showed nuclear pyknosis. In summary, we report the histological findings in benign and malignant prostatic tissues after HIFU treatment. These findings include a spectrum of morphological changes ranging from apparent necrosis to more subtle cellular damage can be observed in benign prostatic tissue after HIFU treatment. There were minimal morphologic changes in residual adenocarcinoma after HIFU treatments. The pathologist should be aware of common histologic findings in prostatic biopsies after HIFU treatment. We recommend routine reporting of Gleason scores in post-HIFU needle biopsies.

Human Amniotic Fluid as a Potential New Source of Organ Specific Precursor Cells for Future Regenerative Medicine Applications

Human amniotic fluid contains multiple cell types, including pluripotent and committed progenitor cells, and fully differentiated cells. We characterized various cell populations in amniotic fluid. Optimum culture techniques for multiple cell line passages with minimal morphological change were established. Cell line analysis and characterization were done with reverse transcriptase and real-time polymerase chain reaction. Immunoseparation was done to distinguish native progenitor cell lines and their various subpopulations. Endodermal and mesodermal marker expression was greatest in samples of early gestational age while ectodermal markers showed a constant rate across all samples. Pluripotent and mesenchymal cells were always present but hematopoietic cell markers were expressed only in older samples. Specific markers for lung, kidney, liver and heart progenitor cells were increasingly expressed after 18 weeks of gestation. We specifically focused on a CD24+OB-cadherin+ population that could identify uninduced metanephric mesenchyma-like cells, which in vivo are nephron precursors. The CD24+OB-cadherin+ cell line was isolated and subjected to further immunoseparation to select 5 distinct amniotic fluid kidney progenitor cell subpopulations based on E-cadherin, podocalyxin, nephrin, TRKA and PDGFRA expression, respectively. These subpopulations may represent different precursor cell lineages committed to specific renal cell fates. Committed progenitor cells in amniotic fluid may provide an important and novel resource of useful cells for regenerative medicine purposes.

INVOLVEMENT OF ILLUMINATION IN INDOCYANINE GREEN TOXICITY AFTER ITS WASHOUT IN THE EX VIVO RAT RETINA

To elucidate the involvement of illumination in indocyanine green (ICG) retinal toxicity. We incubated isolated rat retinas with or without illumination after exposure to 0.5% ICG. We also examined whether a time lag following ICG exposure before illumination altered the damage. Toxicity was evaluated by histologic and biochemical assays, including measurement of lactate dehydrogenase release. Retinas fixed immediately after ICG exposure showed minimal morphologic changes. However, illumination for 3 hours at 34 degrees C starting after washout of ICG selectively damaged the outer nuclear layer. Retinas incubated for 3 hours under the same condition in the dark showed preserved morphology but were damaged by subsequent illumination. When retinas were illuminated after washout of ICG at a lower temperature (30 degrees C), the damage was attenuated. Results obtained using lactate dehydrogenase release were consistent with these morphologic changes. Incubating retinas in the dark and cooling after ICG exposure significantly inhibited retinal damage, suggesting that ICG interacts with illumination to induce retinal damage.

TheArabidopsisMYB5 Transcription Factor Regulates Mucilage Synthesis, Seed Coat Development, and Trichome Morphogenesis

The Arabidopsis thaliana MYB5 gene is expressed in trichomes and seeds, including the seed coat. Constitutive expression of MYB5 resulted in the formation of more small trichomes and ectopic trichomes and a reduction in total leaf trichome numbers and branching. A myb5 mutant displayed minimal changes in trichome morphology, while a myb23 mutant produced increased numbers of small trichomes and two-branched trichomes. A myb5 myb23 double mutant developed more small rosette trichomes and two-branched trichomes than the single mutants. These results indicate that MYB5 and MYB23 regulate trichome extension and branching. The seed coat epidermal cells of myb5 and myb5 myb23 were irregular in shape, developed flattened columellae, and produced less mucilage than those of the wild type. Among the downregulated genes identified in the myb5 seeds using microarray analysis were ABE1 and ABE4 (alpha/beta fold hydrolase/esterase genes), MYBL2, and GLABRA2. The same genes were also downregulated in transparent testa glabra1 (ttg1) seeds, suggesting that MYB5 collaborates with TTG1 in seed coat development. These genes were upregulated in leaves and roots by ectopically expressed MYB5. The MYBL2, ABE1, and ABE4 promoters were active in seeds, including seed coats, and the latter two also in trichomes. Models of the MYB5 regulatory networks involved in seed coat and trichome development are presented.

A δ-Catenin Signaling Pathway Leading to Dendritic Protrusions

Delta-catenin is a synaptic adherens junction protein pivotally positioned to serve as a signaling sensor and integrator. Expression of delta-catenin induces filopodia-like protrusions in neurons. Here we show that the small GTPases of the Rho family act coordinately as downstream effectors of delta-catenin. A dominant negative Rac prevented delta-catenin-induced protrusions, and Cdc42 activity was dramatically increased by delta-catenin expression. A kinase dead LIMK (LIM kinase) and a mutant Cofilin also prevented delta-catenin-induced protrusions. To link the effects of delta-catenin to a physiological pathway, we noted that (S)-3,5-dihydroxyphenylglycine (DHPG) activation of metabotropic glutamate receptors induced dendritic protrusions that are very similar to those induced by delta-catenin. Furthermore, delta-catenin RNA-mediated interference can block the induction of dendritic protrusions by DHPG. Interestingly, DHPG dissociated PSD-95 and N-cadherin from the delta-catenin complex, increased the association of delta-catenin with Cortactin, and induced the phosphorylation of delta-catenin within the sites that bind to these protein partners.

Protective Effect of Saponins from Panax notoginseng against Doxorubicin-Induced Cardiotoxicity in Mice

The dried rhizome of Panax notoginseng is a traditional Chinese herb extensively used for treatment of cardiovascular diseases and other ailments. Panax notoginseng saponins (PNS) are known as the major pharmacologically active constituents. The purpose of this study was to investigate the cardioprotective effects of PNS against doxorubicin-induced cardiotoxicity and its possible influence on the anti-tumor activity of doxorubicin. Five groups of ICR mice were treated with saline (control group), doxorubicin alone (20 mg/kg I. P.), PNS alone, doxorubicin pretreated with PNS (100 mg/kg I. G. for 5 consecutive days) or amifostine (single dose of 200 mg/kg I. V., used as positive control). After 72 h of doxorubicin treatment, cardiac function, serum levels of lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CK-MB) and activities of antioxidant enzymes in heart tissue were measured. Pretreatment with PNS significantly protected the mice from DOX-induced cardiotoxicity as evidenced from improved ventricular contractile function, lower levels of serum LDH, CK and CK-MB, minimal morphological changes in hearts, and normalization of myocardial superoxide dismutase, glutathione peroxidase and catalase activities. Additionally, IN VITRO cytotoxic studies demonstrated that PNS did not compromise the inhibitory effect of doxorubicin on the proliferation of cancer cells. These results imply the potentially clinical application of PNS to overcome the negative side effects of doxorubicin.

Confocal Microscopy of Corneal Wound Healing After Ho:YAG Laser Thermokeratoplasty

To investigate corneal wound healing using confocal microscopy in patients who underwent laser thermokeratoplasty (LTK) for hyperopia between +1.50 and +3.00 diopters (D). In a prospective, nonrandomized study, 78 eyes of 42 patients were followed for 1 year using contact and non-contact confocal microscopy to evaluate corneal appearance after LTK with the Oko-1 Ho: YAG laser. The NIDEK Confoscan 4, 20x non-contact lens and 40x contact lens, was used to evaluate the morphology of the corneal layers. The Oko-1 laser was used to reduce or eliminate hyperopic refractive error. Patients underwent confocal microscopy measurement preoperatively, 1 and 2 weeks and 1, 3, 6, and 12 months after LTK. Individual examinations were reviewed and classified by the investigators. Preoperatively, spherical hyperopia was +2.11 +/- 0.21 D (range: +1.50 to +2.75 D). At 3 months postoperatively, the mean manifest refractive spherical equivalent (MRSE) was +0.11 +/- 0.02 D and +0.21 +/- 0.02 D at 1 year. Mean corneal pachymetry was 631.6 +/- 8.40 microm preoperatively, 637.4 +/- 12.7 microm at 3 months, and 608.4 +/- 31.7 microm at 1 year. The mean endothelial cell density was 2771.4 +/- 28.4 cells/mm2 preoperatively, 2709.4 +/- 122.3 cells/mm2 at 3 months, and 2693.2 +/- 139.1 cells/mm2 at 1 year. Activated keratocytes were present at 3 months postoperatively, which decreased over the course of 1 year. Laser thermokeratoplasty for low to moderate hyperopia using the Oko-1 results in formation of intrastromal fibrosis with minimal changes in corneal morphology outside the sites of treatment.

Increased ischemic injury in old mouse liver: An ATP-dependent mechanism

Although livers exhibit only minimal morphologic changes with age, how older livers tolerate pathologic conditions such as normothermic ischemia is unknown. Young 6-week-old mice and old 60-week-old mice underwent 60 minutes of hepatic ischemia and various periods of reperfusion. Markers of hepatocyte injury, hepatic energy content, and mitochondrial function were determined. Ischemic preconditioning and glucose injection were evaluated as protective strategies against reperfusion injury in old mice. Reperfusion injury was far worse in old mice compared with mice in the young control group. Ischemic preconditioning was highly protective against reperfusion injury in young but not in old mice. Older livers had dramatically reduced adenosine triphosphate (ATP) levels and glycogen contents. The low intrahepatic energy level in old mice was associated with a reduced mitochondrial ATP production. Preoperative injection of glucose restored the intrahepatic ATP content and protected against reperfusion injury. Furthermore, glucose injection restored the protective effect of ischemic preconditioning, resulting in additive protection when both strategies were combined. Aging of the liver is associated with mitochondrial dysfunction and decreased intrahepatic energy content, resulting in poorer tolerance against ischemic injury. Improving intrahepatic ATP levels in old livers by glucose injection protects the old liver against ischemic injury and restores the protective effects of ischemic preconditioning.

Electrochemical behavior of single layer CrN, TiN, TiAlN coatings and nanolayered TiAlN/CrN multilayer coatings prepared by reactive direct current magnetron sputtering

The corrosion behaviors of single layer TiN, CrN, TiAlN and multilayer TiAlN/CrN coatings, deposited on steel substrate using a multi-target reactive direct current magnetron sputtering process, were studied in 3.5% NaCl solution by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). The total thickness of the coatings was about 1.5 μm. About 0.5 μm thick chromium interlayer was used for improved adhesion of the coatings. The potentiodynamic polarization measurements showed that for all the coatings the corrosion potential shifted to higher values as compared to the uncoated substrate. Similarly, the corrosion current density decreased for coated samples, indicating better corrosion resistance of the coated samples. The multilayer coatings of TiAlN/CrN exhibited superior corrosion behavior as compared to the single layer coatings. The Nyquist and the Bode plots obtained from the EIS measurements were fitted by appropriate equivalent circuits to calculate the pore resistance, the charge transfer resistance and the capacitance. These studies revealed that the pore resistance was lowest for TiN coatings, which increased for TiAlN coatings. TiAlN/CrN multilayer coatings exhibited highest pore resistance. No significant change in the capacitive behavior of the coatings was observed, suggesting minimal morphological changes as a result of immersion in the electrolyte. This could be attributed to shorter immersion durations. These studies were confirmed by examining the corroded samples under scanning electron microscope. Preliminary experiments conducted with additional interlayer of electroless nickel (5.0 μm thick) have shown significant improvement in the corrosion resistance of the coatings.

Gender differences in response of hippocampus to chronic glucocorticoid stress: Role of glutamate receptors

Glucocorticoids (GC) play critical roles in the pathophysiological reactions to environmental stress. In brain, morphological changes were examined in hippocampal CA3 neurons with 2 weeks of chronic elevation of GC in male and female mice. Molecular correlates and underlying mechanisms paralleling these morphologic changes in hippocampus were investigated. Although the hippocampal neurons in the CA3 area in male mice atrophy with chronically elevated GC, female mice show minimal morphological changes with comparable GC regimens. These sexual morphological differences correlate with differences in the postsynaptic dense protein (PSD95) as well as the spectrum of glutamate receptors induced by GC treatment in male and female mice, including NMDA, AMPA, and KA receptors. These findings suggest that synaptic receptor composition is adapted to the unique physiological requirements of males and females and illuminate underlying mechanisms of GC/stress responses in the brain.

Stability of Aqueous Suspensions of Titanate Nanotubes

The long-term stability of titanate nanotubes, which were produced by alkaline hydrothermal treatment of TiO2, was studied at room temperature in acidic, pure water, and basic aqueous suspensions. In pure water and basic (0.1 mol dm-3 NaOH) solutions, the nanotubes were stable and minimal morphological changes occurred. In 0.1 mol dm-3 H2SO4, suspended titanate nanotubes slowly transformed to rutile nanoparticles of ca. 3 nm size, which were agglomerated into ellipsoidal particles. The porosity, crystal structure, and morphology of protonated titanates and TiO2 have been studied for intermediate states during the transformation by nitrogen adsorption, XRD, Raman spectroscopy, SEM, and HRTEM. The rate of conversion of nanotubes to nanoparticles has been related to the concentration of soluble titanium(IV) in solution, which depends on the nature of the acid. Thermodynamic and kinetic aspects of the acid transformation are discussed.

Cognitive impairment following status epilepticus and recurrent seizures during early development: support for the “two-hit hypothesis”

Prolonged seizures in immature rats result in minimal behavioral consequences when the animals are studied later in life. Likewise, early-onset seizures are associated with minimal morphological changes. However, it is known that seizures early in life result in changes in the brain that make it more vulnerable to subsequent seizure-induced injury (the so-called two-hit hypothesis). Whether this heightened vulnerability occurs immediately after the first seizure is not known. In this study, immature rats were exposed to status epilepticus (SE) followed by a series of 25 flurothyl-induced seizures, SE alone, 25 flurothyl-induced seizures alone, or no seizures. Rats exposed to SE and flurothyl seizures performed significantly poorer in the water maze 2 weeks following the last seizure compared with the other groups. No histological lesions were seen in any of the four groups. This study suggests that SE renders the immature brain vulnerable to further seizure-induced injury and this enhanced vulnerability occurs very quickly after the SE.

Subchronic inhalation study of stone wool fibres in rats.

Pathology results after subchronic inhalation in rats of three separate fibres representing the new biosoluble high-aluminium low-silica HT type stone wool are given, and the results were compared with the results from a similar study done with the traditional stone wool MMVF21. Male Wistar rats were exposed at one exposure level by nose-only inhalation to well-characterized fibre test atmospheres. The fibres had been size selected to be largely rat respirable. The target dose was an exposure to 150 long fibres/ml (length>20 microm) in each group, and this dose was achieved for all the fibres. The negative control groups were exposed to filtered air. The exposure duration was 6 h/day, 5 days/week for 3 months, with a subsequent non-exposure period lasting 3 months. The rats were killed 1 week after the last exposure and additional post-exposure kills were performed at 1.5 and 3 months to monitor the progression of pulmonary change and fibre numbers in the lung. The assessments included bronchoalveolar lavage fluid (BALF) for evaluation of inflammatory response (e.g. protein content, enzymes, increase in polymorphonuclear leucocytes) and measurement of cell proliferation, assessment of early fibrosis through histological examination and comparison of body weight and lung lobe weights. After exposure of rats to the new biosoluble fibres no biologically significant effects were observed except that a statistically significant increase in lung weight was observed up to 1.5 months post-exposure in all three treatment groups. At 3 months post-exposure, the small increase was no longer significant. The increase in lung weight was still present in the MMVF21 group at the 3 months post-exposure kill. After 3 months exposure, lung retention of long fibres (length>20 microm) varied from 0.4 to 5.2 x 10(6) per lung for the biosoluble fibres. At 3 months post-exposure, the long fibre concentration in the lungs had decreased to 1-7% of this figure. The fibre with the relatively highest biopersistence (RIF41001) showed the highest fibre retention. The retention of the more biopersistent traditional stone wool MMVF21 was 5.7 x 10(6) per rat lung after 3 months exposure and had decreased to 64% of this figure at 3 months post-exposure. There was no clear difference in the bronchoalveolar lavage fluid cell concentration and percentage of cells between MMVF21 and the HT groups. Fibre inhalation caused a significant increase after 3 months in all the biochemical parameters measured in the BALF. Cell proliferation was enhanced at the end of exposure for MMVF21 for all three labelling indices, but only for the bronchiolar epithelium in the RIF41001 group and for alveolar parenchymal cells in the RIF43006-1 group. At the termination of the 3 month exposure period, as well as after 1.5 and 3 month recovery periods, minimal morphological changes were diagnosed in the biosoluble fibre groups. These changes included alveolar macrophage aggregation and/or microgranulomas at the bronchiolar-alveolar junction in the few rats affected. No fibrogenic potential was noted for any of the three fibres. No clear-cut difference between the different biosoluble fibre types was noted. In the MMVF21 group, minimal interstitial fibrosis was observed that gradually decreased after the 1.5 and 3 month non-exposure periods. In this study, the pathological changes found in the lungs of exposed rats were in accordance with the pathology previously reported from full lifespan inhalation studies. This may indicate that for fibres belonging to the man-made vitreous fibres group a well conducted biopersistence study is sufficient to predict possible pathogenic effects for new fibre types. The biological parameters examined in a 90 day study may indicate little additional information to contribute to the prediction of the outcome of carcinogenicity studies.

Changes in the local morphology of the rectus abdominis muscle following the DIEP flap: an ultrasonographic study

This study was undertaken to assess the changes in the local morphology of the rectus abdominis muscle following intramuscular dissection of the deep inferior epigastric artery perforators after harvesting of the deep inferior epigastric peroforator (DIEP) flap. While the DIEP provides the well-known advantage of use of the lower abdominal tissue with preservation of the integrity of the abdominal wall musculature, postoperative problems such as abdominal asymmetry, bulges and reduced flexion capacity have been found. These changes may be due to rectus abdominis muscle damage from ischemia or denervation. We used ultrasonography to assess the changes in rectus abdominis muscle thickness and contractility, preoperatively, 1-month and 1-year postoperatively. The study group consisted of 17 rectus abdominis muscles in 14 patients subjected to intramuscular dissection of perforators. The control group consisted of 11 intact rectus abdominis muscles in 11 patients who had undergone unilateral DIEP flap elevation, the dissected muscles being part of the study group. We found that the resting muscle thickness in the study group was, significantly increased at 1-month postoperatively, resolving by 1-year follow-up. As these changes were not seen in the control group, the increased muscle thickness is attributed to postoperative oedema that resolves with time. All muscles in the study and control groups retained contractility showing no evidence of muscle denervation. Our date demonstrates that intramuscular dissection of perforator vessels in the DIEP flap leads to minimal changes in the local morphology and contractility of the rectus abdominis muscle.

Hepatocyte growth factor and its role in the pathogenesis of retinal detachment.

Hepatocyte growth factor (HGF) regulates barrier function of retinal pigment epithelial (RPE) cells. The purpose of this study was to determine whether overexpression of HGF in the RPE induces retinal detachment (RD). E1/E3-deleted adenoviral vectors encoding HGF (Ad CMV.HGF), green fluorescent protein (Ad CMV.GFP), or connective tissue growth factor (AdCMV.CTGF) were injected subretinally in adult pigmented rabbits (5 x 10(4) plaque-forming units [pfu]/eye). Animals were observed for up to 28 days with fundus photography. HGF expression in the retina and vitreous was determined using immunohistochemistry, and ELISA. Histopathologic examinations were performed with light and electron microscopy. Control eyes injected with AdCMV.GFP showed GFP expression almost exclusively in the RPE monolayer. Eyes injected with AdCMV.HGF showed strong HGF immunopositivity in RPE cells at the injection site. Elevated HGF levels were found in the vitreous peaking at postinjection day 7, diminishing to baseline by postinjection day 28. Eyes injected with AdCMV.HGF developed chronic RD and chronic inflammation in the choroid within the time frame of HGF expression. Groups of proliferating RPE cells were seen in the subretinal space in the region of the RD, and in some cases multilayered cellular membranes developed. No RD and minimal morphologic changes were seen in the eyes injected with AdCMV.GFP or AdCMV.CTGF. Overexpression of HGF in RPE induces chronic, serous RD with subretinal proliferation of RPE. This work provides insight into the pathogenesis of RD and suggests that HGF should be further investigated as a target for therapeutic intervention in RD.

Ultrastructural and Morphometric Comparison of Retinal and Myocardial Capillaries Following Acute Ischaemia

The recovery of any tissue following a period of ischaemia is dependent on a patent microvasculature to restore blood flow. In the ischaemic myocardium, a reduction in capillary cross-sectional dimensions occurs, which is likely to contribute to “no-reflow” injury. Clinical and experimental evidence indicates that the retina is able to tolerate moderate periods of ischaemia without significant loss of function. The aim of the present study is to test the hypothesis that, as an end-arterial system, the retina possesses compensatory processes to maintain a functional microcirculation following acute ischaemia. Thirty minutes of no-flow global ischaemia was induced in isolated hearts of Wistar rats without reperfusion. The retina was also made ischaemic for 30 min using two experimental models: microsphere embolization and anoxic superfusion. Changes in capillary dimensions were assessed by ultrastructural morphometry. Following 30 min of myocardial ischaemia capillaries appeared swollen with a significant reduction in total capillary and luminal cross-sectional area. By contrast, ischaemic retinal capillaries showed minimal morphological changes and no significant alteration in dimensions. We have demonstrated notable differences in the response of retinal and myocardial microvessels to acute ischaemia. It is likely that the maintenance of capillary patency following short periods ischaemia in the retina is part of an adaptive mechanism to protect visual function.

Effects of intense pulsed light on sun-damaged human skin, routine, and ultrastructural analysis.

New, non-ablative methods can be used in skin rejuvenation. Histologic analysis of non-ablative IPL effects on facial, sun-damaged skin. Five female subjects, wrinkle class I or II and Fitzpatrick skin types I, II, and III. IPL treatment: once monthly, 560-nm cut-off filters, spot size 8x35 mm, 28-36 J/cm. Routine histology or electron microscopy on 2-mm punches, before treatment and then 1 week, 3 months, and 12 months. Pre-treatment specimens contained solar elastosis and perifollicular lymphoid infiltrates. Collagen and elastic fibers appeared unaffected by treatment. At 1-week, Demodex organisms appeared coagulated. Under these conditions, IPL induces minimal morphologic changes in mildly sun-damaged skin. Some esthetic improvement may be secondary to clearing of Demodex organisms and reduction of associated lymphocytic infiltrate.

Fetal aortic isthmus growth and morphology in late gestation.

To establish normal values for fetal aortic isthmus diameter in late gestation and to identify any changes in aortic isthmus dimensions and morphology in pathological conditions. In this prospective study, the fetal aortic isthmus was evaluated in 110 low-risk pregnant women at between 30 and 40 weeks of gestation and 42 pregnant women who were at high risk for congenital heart defects. From coronal echocardiographic images of the connection between the aorta and ductus arteriosus, the internal diameter of the aorta was measured at the middle of the isthmus, at the point of the isthmus just proximal to the entry of the ductus arteriosus and at the descending aorta below the entry of the ductus arteriosus. Correlation coefficients for the diameter of each aortic segment when related to gestational age varied from r = 0.60 to r = 0.80 (P < 0.001 for each), and growth curves were derived from the third and 97th percentiles about each linear regression analysis. The mean and the third percentile for the ratio of the isthmus just proximal to the entry of the ductus arteriosus to the middle of the isthmus were 1 and 0.81. In one fetus of the high-risk patients, a contraductal shelf and the accompanying area of tubular isthmic hypoplasia were suspected and a diagnosis of coarctation of the aorta was subsequently confirmed after birth. In two fetuses with growth restriction and one fetus with intestinal atresia, the isthmus diameters were below the third percentile but the ratios of the isthmus end to the middle of the aortic isthmus were all normal and no cardiac anomalies were detected after birth. We could establish normal values for aortic isthmus diameters in late gestation from a coronal view and identify even minimal changes in aortic isthmus dimensions and morphology in pathological conditions.

Differences in cytokine and chemokine responses during neurological disease induced by polytropic murine retroviruses Map to separate regions of the viral envelope gene.

Infection of the central nervous system (CNS) by several viruses can lead to upregulation of proinflammatory cytokines and chemokines. In immunocompetent adults, these molecules induce prominent inflammatory infiltrates. However, with immunosuppressive retroviruses, such as human immunodeficiency virus (HIV), little CNS inflammation is observed yet proinflammatory cytokines and chemokines are still upregulated in some patients and may mediate pathogenesis. The present study examined expression of cytokines and chemokines in brain tissue of neonatal mice infected with virulent (Fr98) and avirulent (Fr54) polytropic murine retroviruses. While both viruses infect microglia and endothelia primarily in the white matter areas of the CNS, only Fr98 induces clinical CNS disease. The pathology consists of gliosis with minimal morphological changes and no inflammation, similar to HIV. In the present experiments, mice infected with Fr98 had increased cerebellar mRNA levels of proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha), TNF-beta, and interleukin-1 alpha and chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, monocyte chemoattractant protein 1 (MCP-1), gamma-interferon-inducible protein 10 (IP-10), and RANTES compared to mice infected with Fr54 or mock-infected controls. The increased expression of these genes occurred prior to the development of clinical symptoms, suggesting that these cytokines and chemokines might be involved in induction of neuropathogenesis. Two separate regions of the Fr98 envelope gene are associated with neurovirulence. CNS disease associated with the N-terminal portion of the Fr98 env gene was preceded by upregulation of cytokines and chemokines. In contrast, disease associated with the central region of the Fr98 env gene showed no upregulation of cytokines or chemokines and thus did not require increased expression of these genes for disease induction.