Social environment as a modulator of immunosenescence.

Immune system aging, a process known as immunosenescence, involves a striking rearrangement affecting all immune cells, resulting in an increased rate of infections and a major incidence of autoimmune diseases and cancer. Nonetheless, differences in how individuals of the same chronological age carry out this immunosenescence establishment and thus the aging rate have been reported. In the context of neuroimmunoendocrine communication and its role in the response to stress situations, growing evidence suggests that social environments profoundly influence all physiological responses, especially those linked to immunity. Accordingly, negative contexts (loneliness in humans/social isolation in rodents) were associated with immune impairments and decreased lifespan. However, positive social environments have been correlated with adequate immunity and increased lifespan. Therefore, the social context in which an individual lives is proposed as a decisive modulator of the immunosenescence process and, consequently, of the rate of aging. In this review, the most important findings regarding how different social environments (negative and positive) modulate immunosenescence and therefore the aging rate, as well as the role of stress responses, hormesis, and resilience in these environments will be explained. Finally, several possible molecular mechanisms underlying the effects of negative and positive environments on immunosenescence will be suggested.

The use of a bed with an insulating system of electromagnetic fields improves immune function, redox and inflammatory states, and decrease the rate of aging.

BACKGROUND: The immune system, as a homeostatic system, is an excellent marker of health and has also been proposed as an indicator of the rate of aging. The base of the age-related changes in the immune system, "immunosenescence", is oxidative-inflammatory stress. Studies have shown that long-term exposure to electromagnetic fields (EMFs) produced by technology causes inhibitory effects on the immune response and increases oxidation. The aim of the present study was to investigate the effects of resting on an EMF-insulated system on several immune functions, the oxidative-inflammatory state and subsequently the rate of aging (biological age). METHODS: Several immune functions, in peripheral blood neutrophils and mononuclear cells, of 31 volunteers were analyzed before and after 2 months of using a bed with the patented HOGO system, which insulated participants against EMFs. Several oxidative and inflammatory parameters, in whole blood cells, were also studied. The biological age was calculated using a mathematical formula, which was based on several immune function parameters. A placebo group of 11 people using beds without that property were used as a control. RESULTS: The results showed a significant improvement of immune functions and antioxidant and anti-inflammatory defenses after using the HOGO system for 2 months. In addition, a decrease in oxidants and pro-inflammatory compounds, a lowering of oxidative damage in lipids and in DNA as well as a reduction of calculated biological age was also observed. The placebo group did not show any changes. CONCLUSIONS: In conclusion, 2 months of resting on a bed insulated from EMFs demonstrates improvement in immune function, oxidative-inflammatory state and biological age.

Parathyroid hormone-related protein exhibits antioxidant features in osteoblastic cells through its N-terminal and osteostatin domains.

OBJECTIVES: Oxidative stress plays a major role in the onset and progression of involutional osteoporosis. However, classical antioxidants fail to restore osteoblast function. Interestingly, the bone anabolism of parathyroid hormone (PTH) has been shown to be associated with its ability to counteract oxidative stress in osteoblasts. The PTH counterpart in bone, which is the PTH-related protein (PTHrP), displays osteogenic actions through both its N-terminal PTH-like region and the C-terminal domain. METHODS: We examined and compared the antioxidant capacity of PTHrP (1-37) with the C-terminal PTHrP domain comprising the 107-111 epitope (osteostatin) in both murine osteoblastic MC3T3-E1 cells and primary human osteoblastic cells. RESULTS: We showed that both N- and C-terminal PTHrP peptides at 100 nM decreased reactive oxygen species production and forkhead box protein O activation following hydrogen peroxide (H2O2)-induced oxidation, which was related to decreased lipid oxidative damage and caspase-3 activation in these cells. This was associated with their ability to restore the deleterious effects of H2O2 on cell growth and alkaline phosphatase activity, as well as on the expression of various osteoblast differentiation genes. The addition of Rp-cyclic 3',5'-hydrogen phosphorothioate adenosine triethylammonium salt (a cyclic 3',5'-adenosine monophosphate antagonist) and calphostin C (a protein kinase C inhibitor), or a PTH type 1 receptor antagonist, abrogated the effects of N-terminal PTHrP, whereas protein phosphatase 1 (an Src kinase activity inhibitor), SU1498 (a vascular endothelial growth factor receptor 2 inhibitor), or an anti osteostatin antiserum, inhibited the effects of C-terminal PTHrP. CONCLUSION: These findings indicate that the antioxidant properties of PTHrP act through its N- and C-terminal domains and provide novel insights into the osteogenic action of PTHrP.Cite this article: S. Portal-Núñez, J. A. Ardura, D. Lozano, I. Martínez de Toda, M. De la Fuente, G. Herrero-Beaumont, R. Largo, P. Esbrit. Parathyroid hormone-related protein exhibits antioxidant features in osteoblastic cells through its N-terminal and osteostatin domains. Bone Joint Res 2018;7:58-68. DOI: 10.1302/2046-3758.71.BJR-2016-0242.R2.

The role of Hsp70 in oxi-inflamm-aging and its use as a potential biomarker of lifespan.

The heat-shock protein 70 (HSPA1A or Hsp70) acts as a cellular defense mechanism its expression being induced under stressful conditions. Aging has been related to an impairment in this induction. However, an extended longevity has been associated with its increased expression. According to the oxidation-inflammation theory of aging, chronic oxidative stress and inflammatory stress situations (with higher levels of oxidant and inflammatory compounds and lower antioxidant and anti-inflammatory defenses) are the basis of the age-related alterations of body cells. Since oxidation and inflammation are interlinked processes, and Hsp70 has been shown to confer protection against the harmful effects of oxidative stress as well as modulating the inflammatory status, it could play a role as a regulator of the rate of aging. This role may be different in mitotic and post-mitotic tissues due to the differences in their age-related mechanisms of response, such as apoptosis. Mechanisms affected by Hsp70 that can interfere with the deleterious effects of excessive oxidative stress and chronic low-grade inflammation and that are closely related to the aging process have been detailed. In addition, the potential use of the basal levels (with their differences in post-mitotic and mitotic tissues), the inducible levels, as well as the extracellular levels of Hsp70 as possible biomarkers of the rate of aging and lifespan, have also been discussed.

A torque removal study on the primary stability of orthodontic titanium screw mini-implants in the cortical bone of dog femurs.

The aim of this study was to biomechanically evaluate the primary stability of pure titanium orthodontic mini-implants, inserted into pre-drilled cavities of differing diameters. Mini-implants (1.2 mm diameter) were placed into 1.0 mm and 1.2 mm diameter cavities prepared in the mid-region of the bilateral hind leg femurs of anesthetized beagles. Removal torque strengths were measured immediately, 1, 3, 6, 9 and 12 weeks post-insertion of the implant. For mini-implants placed into 1-mm cavities, removal torque values decrease over the first 6 weeks (p<0.01), after which values remained static. Average values obtained immediately, 1, 3 and 6 weeks post-insertion were 10.98, 8.83, 7.20 and 5.12 Ncm, respectively . Immediately post-insertion, removal torque values of mini-implants placed in a 1.2-mm cavity, were 11-fold lower than those placed in 1.0-mm cavities, which then demonstrated a significant increase in strength from 3 weeks (1.35 Ncm) to 6 weeks (5.17 Ncm) post-insertion (p<0.01). Measurements 6, 9 and 12 weeks post-insertion were similar to those in the 1.0-mm cavity. Initial stability of titanium mini-implants is considered necessary for immediate and early use in orthodontics, and an implant without this initial stability should be replaced or isolated until it develops the appropriate stability supported by osseointegration.

Tissue Doppler-derived index of left ventricular filling pressure, E/E', predicts survival of patients with non-valvular atrial fibrillation.

OBJECTIVES: To investigate whether the ratio of early transmitral flow velocity (E) to early diastolic mitral annular velocity (E') predict prognosis in patients with non-valvular atrial fibrillation. METHODS: 230 patients with non-valvular atrial fibrillation were enrolled and studied. According to E/E' value, patients were divided into groups with lower (group A with E/E' 15) E/E'. RESULTS: During follow up (average 245 days), 21 (9.1%) deaths were documented. All cause death (15/90 (16.7%) v 6/140 (4.3%)), cardiac death (10 (11.1%) v 2 (1.4%)) and congestive heart failure (16 (17.8%) v 8 (5.7%)) were more common in group B than in group A (all p < 0.01). A Kaplan-Meier survival curve showed that the cumulative survival rate was significantly lower in group B than in group A (log rank p = 0.0013). By multivariate logistic regression analysis, E/E' (chi(2) = 4.47, odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01 to 1.11, p = 0.03) and age (chi(2) = 6.45, OR 1.06, 95% CI 1.01 to 1.11, p = 0.02) were independent predictors of mortality. CONCLUSION: The Doppler-derived index of left ventricular filling pressure, E/E', is a powerful predictor of the clinical outcome of patients with non-valvular atrial fibrillation.

Acute haemodynamic benefits of biatrial atrioventricular sequential pacing: comparison with single atrial atrioventricular sequential pacing.

OBJECTIVE: To evaluate the acute effects on haemodynamic variables of biatrial pacing in comparison with high right atrial (HRA) pacing and left lateral atrial pacing. PATIENTS AND DESIGN: 23 patients were paced from the HRA site, the lateral site of the coronary sinus (CS), and both sites on two fixed atrioventricular delays (100 and 150 ms) during atrioventricular sequential pacing at 80 and 100 beats/min in random order. MAIN OUTCOME MEASURES: After five minute pacing, the maximum P wave duration on a 12 lead ECG, cardiac output, pulmonary capillary wedge pressure, and the transmitral flow pattern by transthoracic echocardiography were measured. RESULTS: Biatrial pacing delivered the shortest P wave duration (133 (25) ms, 133 (27) ms, and 96 (15) ms during HRA, CS, and biatrial pacing, respectively; p < 0.001), and the most improvement in cardiac output and pulmonary capillary wedge pressure (3.71 (0.93) l/min and 15 (7) mm Hg, 3.79 (0.97) l/min, and 14 (6) mm Hg, and 4.09 (1.01) l/min and 13(6) mm Hg during HRA, CS, and biatrial pacing, respectively; p < 0.01). Biatrial pacing most significantly decreased the intervals between the atrial pacing spike and the peak and end of the atrial filling wave (186 (16) ms and 250 (22) ms, 172 (19) ms and 242 (24) ms, and 153 (15) ms and 227 (23) ms during HRA, CS, and biatrial pacing, respectively; p < 0.001). It also significantly increased the mitral flow time velocity integral and peak atrial filling wave velocity (7.5 (3.4) cm and 63.8 (17.6) cm/s, 7.8 (3.0) cm and 62.4 (16.6) cm/s, and 8.3 (3.4) cm and 67.8 (19.3) cm/s during HRA, CS, and biatrial pacing, respectively; p < 0.05). The improvements in haemodynamic variables were especially remarkable in patients who had a longer interatrial conduction delay. CONCLUSIONS: Biatrial pacing yielded the most significant improvements in haemodynamic variables. These haemodynamic benefits may play a part in reducing intra-atrial pressure and preventing atrial fibrillation.

Real time quantification of low temperature radiofrequency ablation lesion size using phased array intracardiac echocardiography in the canine model: comparison of two dimensional images with pathological lesion characteristics.

OBJECTIVE: To evaluate the feasibility of quantifying low temperature radiofrequency catheter ablation (RFCA) lesions using a phased array intracardiac echocardiography (ICE) catheter--with better tissue penetration and in a deflectable device-in the canine model. INTERVENTION: Low temperature radiofrequency (RF) energy (50-60 degrees C at up to 40 W) was delivered to the left ventricle in 11 beagles for 60 seconds, using an 8 French catheter with a deflectable tip and a 4 mm distal electrode. MAIN OUTCOME MEASURES: Comparison of the width and depth of RFCA lesions measured by ICE with pathological findings. RESULTS: 33 RF energies were delivered in 11 dogs. 31 lesions (94%) were confirmed at necropsy. 27 of 31 ablation lesions (87%) were detected by ICE. The mean (SD) width and depth of the ICE detected lesions were 10.4 (2.6) mm and 5.7 (1.9) mm, respectively. Pathological findings showed that RFCA lesions consisted of inner and outer layers. Macroscopically, the mean (SD) width and depth of the inner layers were 7.6 (2.3) mm and 3.6 (1.2) mm and those for the whole layers were 10.0 (2.8) mm and 5.3 (1.5) mm, respectively. Microscopically, the inner and outer layers corresponded to necrotic and oedematous areas, respectively. The ICE detected lesion size had better correlation with the pathological measurements of the whole layers in width (r = 0.911) and in depth (r = 0.756). CONCLUSION: The real time evaluation of RFCA lesion size using the phased array ICE is feasible, even with a low temperature RF application. However, ICE slightly overestimates RFCA lesion size compared with pathological necrotic lesion size.

Facial subdermal vascular network flap: anatomic study and clinical application.

Despite the numerous flaps for facial reconstruction that have been described, the search for the ideal flap with good color matching and minimal donor-site morbidity continues. In the past 3 years we have repaired 13 facial defects with success using the lateral genicervical flap - a type of facial subdermal vascular network flap (SVNF) - with a pedicle located on the preauricular region. An anatomic study of the facial SVNF, including blood supply and vascular distribution of the face and anatomic characteristics of facial vessels, based on 14 cadaver dissections, was carried out. The blood supply of the facial skin basically originated from the branches of the facial, superficial temporal and infraorbital arteries. The lateral genicervical skin was supplied basically by the branches of the facial, superficial temporal and occipital arteries, but also by the terminal branches of the superior thyroid artery. The branches diverging from these arteries became superficial and formed a subcutaneous arterial network. The arterioles from the network went to the corium layer and formed a subdermal arterial network whose arterioles anastomosed with each other in a honeycomb-like structure. The vascular distribution presented certain directivity on different areas. The blood supply of the pedicle originated from the subdermal vascular network formed by the perforator branches of these arteries. The arterioles from the facial and superficial temporal arteries anastomosed in the lateral genicervical region. From the anatomic study, we think that the viability of the facial SVNF depends basically on the subdermal vascular network formed by the perforator branches of the pedicle, and that the anastomoses between the facial and superficial temporal arteries provide a solid anatomic basis to the lateral genicervical flap. The clinical data also indicated that this flap is a useful alternative for facial, especially superficial temporal, defects. But the directivity must be taken into account in its clinical application.

New applications of intracardiac echocardiography: assessment of coronary blood flow by colour and pulsed Doppler imaging in dogs.

OBJECTIVE: To explore the application of a new 10 French intracardiac echocardiography (ICE) catheter with phased array and Doppler capable transducer for the assessment of epicardial and intramyocardial coronary blood flow. METHODS: The coronary arteries were detected by cross sectional imaging in seven closed chest dogs, and coronary blood flow visualised by colour Doppler. Blood flow velocities were recorded by pulsed Doppler at baseline for reproducibility of repeated measurements, and during hyperaemia for coronary flow reserve measurements. Comparisons were made with Doppler guide wire data obtained simultaneously. Intramyocardial coronary artery blood flow was assessed by colour flow mapping, and the blood flow velocities recorded using pulsed Doppler at baseline and during hyperaemia. RESULTS: Seven left main, six left anterior descending, seven left circumflex, and five right coronary arteries were visualised in the seven animals by cross sectional or colour Doppler imaging. Repeated measurements of coronary flow velocity showed a good correlation (mean diastolic velocity, r = 0.93, n = 22, p < 0.0001; peak diastolic velocity, r = 0.96, n = 22, p < 0.0001, respectively). Intraobserver/interobserver variability was satisfactorily low. Coronary flow reserve from ICE correlated highly with the value obtained from the Doppler guide wire (r = 0.90, n = 26, p < 0.0001). Intramyocardial coronary blood flow was identified in all seven dogs, and flow velocities were recorded at baseline and during hyperaemia in four animals. CONCLUSIONS: This new ICE catheter provides high quality diagnostic resolution. It is useful for coronary blood flow assessment.

Allergic conjunctivitis as a risk factor for laser in situ keratomileusis.

PURPOSE: To analyze the effect of allergic conjunctivitis (AC) on the outcome of laser in situ keratomileusis (LASIK) in myopic eyes. SETTING: Minamiaoyama Eye Clinic, Tokyo, Japan. METHODS: Patients who had LASIK were divided into 2 groups: those with AC (84 eyes of 49 patients; the allergic group) and those without AC (140 eyes of 77 patients; the nonallergic group). Allergic conjunctivitis was diagnosed clinically by symptoms of eye itching and clinical findings such as papillary proliferation on the tarsal conjunctiva. Preoperative and postoperative uncorrected visual acuity (UCVA) and refraction and intraoperative and postoperative complications were compared. RESULTS: There were no significant differences in UCVA and refraction between the 2 groups. No complications were observed in the allergic group. Intraoperative conjunctival chemosis (3 eyes of 2 patients) and a postoperative epithelial defect that resulted in epithelial ingrowth (1 eye) were observed in the nonallergic group. CONCLUSION: The findings suggest that AC is not a risk factor for LASIK.

Dry eye after laser in situ keratomileusis.

PURPOSE: To determine whether patients undergoing laser in situ keratomileusis have postoperative dry eye. METHODS: In this retrospective, interventional case series, 124 eyes of 64 consecutive patients who underwent laser in situ keratomileusis were examined for a dry eye symptom, Schirmer test with anesthesia, tear clearance rate, tear break-up time, vital staining for ocular surface, corneal sensitivity, and blink rate. All values were compared before and after surgery (1 month, 3 months, 6 months, and 1 year) and values of P <.05 were considered statistically significant. RESULTS: Subjective score for dryness was increased after laser in situ keratomileusis. Tear function index (Schirmer value/tear clearance rate) and break-up time were decreased until 1 month (tear function index) and 3 months (break-up time) after laser in situ keratomileusis but recovered to preoperative levels thereafter. Fluorescein and rose bengal scores were unchanged at all follow-up points except for improvement of the rose bengal score at 6 months. Corneal sensitivity was decreased at 1 month and 3 months, and returned to the preoperative level at 6 months after laser in situ keratomileusis. Blink rate was decreased at 3 months, 6 months, and 1 year after laser in situ keratomileusis. CONCLUSIONS: Patients undergoing laser in situ keratomileusis develop dry eye with compromised tear function for at least 1 month after surgery. Use of artificial tears in the early postoperative period may help to prevent unwanted symptoms and ocular surface damage.

Effect of laser in situ keratomileusis correction on contrast visual acuity.

PURPOSE: To evaluate the changes in contrast visual acuity (CVA) based on the amount of myopic correction with laser in situ keratomileusis (LASIK). METHODS: In this prospective study, patients with myopia ranging from -2.0 to -14.0 diopters (D) were divided into 2 groups: those with myopia less than -6.0 D (n = 20) and those with myopia greater than -6.0 D (n = 13). The CVA was measured preoperatively and 1 week and 1 and 3 months postoperatively using Variable Contrast Visual Acuity Charts. RESULTS: The patients with less than -6.0 D of myopia had a CVA decrease of 15% 1 week postoperatively, which recovered by 1 month, and a decrease of 2.5% 1 week and 1 month postoperatively, which recovered by 3 months. The patients with more than -6.0 D of myopia had a decrease of 15% and 2.5% at all postoperative times. CONCLUSIONS: After LASIK to correct myopia of greater than -6.0 D, there may be a persistent decrease in intermediate and low CVA. Patients should be informed preoperatively of this possible decrease in CVA.

Laser in situ keratomileusis: association with increased width of palpebral fissure.

PURPOSE: To report the preoperative and postoperative palpebral fissure width in eyes undergoing laser in situ keratomileusis. METHODS: In a prospective study, 165 consecutive eyes of 87 patients (41 men and 46 women with a mean +/- standard deviation age of 32.9 (+/-9.5) years) had laser in situ keratomileusis using a Summit (Waltham, MA) APEX PLUS excimer laser and a Moria (Antony, France) LSK microkeratome. The width of palpebral fissure was measured preoperatively, 3 months or 6 months after laser in situ keratomileusis. Patients were classified into three groups as follows: hard contact lens users group (n = 61), soft contact lens users group (n = 63), and non-contact lens users group (n = 41). RESULTS: The average width of palpebral fissure increased after laser in situ keratomileusis in all three groups. The hard contact lens users group increased from 7.6 (+/-1.6) mm to 8.7 (+/-1.2) mm (P <.0001) and non-contact lens users group increased from 7.7 (+/-1.9) mm to 8.9 (+/-1.9) mm (P <.0001). CONCLUSION: These results suggest that laser in situ keratomileusis may be associated with an increase in the width of the palpebral fissure.

Dobutamine stress electrocardiography-gated Tc-99m tetrofosmin SPECT for detection of viable but dysfunctional myocardium.

BACKGROUND: Technetium-99m-labeled myocardial perfusion tracers allow simultaneous assessment of myocardial perfusion and left ventricular function by electrocardiography-gated scan. This study was performed to determine whether dobutamine stress electrocardiography-gated tetrofosmin single photon emission computed tomography (SPECT) can identify viable (as defined by positron emission tomography [PET]) but dysfunctional myocardium with contractile reserve. METHODS AND RESULTS: Thirty-five patients with myocardial infarction underwent resting electrocardiography-gated SPECT and fluorodeoxyglucose (FDG) PET. The relative uptakes of tetrofosmin (%tetrofosmin) and FDG (%FDG) were calculated. Wall motion in 9 left ventricular segments was assessed at rest and during dobutamine stress on a 3-dimensional cine-mode display created with automatic left ventricular function analysis software. A total of 129 dysfunctional segments were analyzed. Forty-five (48.9%) of 92 segments with %tetrofosmin of 50% or greater and only 4 (10.8%) of 37 segments with %tetrofosmin less than 50% had contractile reserves (P <.0001). The sensitivity, specificity, and predictive accuracy of %tetrofosmin of 50% or greater for detecting %FDG of 50% or greater were 85.7%, 74%, and 82.9%, respectively. The incidence of the presence of contractile reserve rose with increasing magnitude of %FDG. The sensitivity, specificity, and predictive accuracy of the presence of contractile reserve for detecting %FDG of 50% or greater were 43.9%, 80.6%, and 52.7%, respectively. CONCLUSIONS: Dobutamine stress electrocardiography-gated SPECT can identify viable (as defined by PET) but dysfunctional myocardium with contractile reserve.

Lack of evidence for an increased microchimerism in the circulation of patients with Sjögren's syndrome.

OBJECTIVE: To examine the hypothesis that fetal microchimerism plays a part in the pathogenic process of Sjögren's syndrome (SS). METHODS: Genomic DNA samples were extracted from peripheral blood whole nucleated cells and the CD34+ cell enriched fraction of patients with SS and healthy women who had male offspring as well as nulliparous women. A Y chromosome-specific sequence was detected as a marker for fetal cells by a nested polymerase chain reaction (PCR) and by DNA hybridisation combined with PCR using specific primers and probes. All procedures were performed with great care to avoid the contamination of male DNA. RESULTS: A nested PCR and DNA hybridisation combined with PCR was established that can detect a single male cell out of 1.67x10(5) female cells. It was not possible to increase the sensitivity further because the amount of template DNA held in the PCR was limited. When these methods were used, no fetal cells were detected in any samples from patients with SS, though they were detected in whole nucleated cells from two healthy women who had delivered sons previously. CONCLUSIONS: The findings indicate that circulating fetal cells in patients with SS are uncommon (<1 in 1.67x10(5)), if they exist. With the conventional PCR based methods that were used, it is difficult to evaluate the quantitative difference in circulating fetal cells between patients with SS and healthy women.

A significant role of stromal fibroblasts in rapidly progressive dry eye in patients with chronic GVHD.

PURPOSE: To elucidate histopathologic features of the lacrimal gland in chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. METHODS: Lacrimal gland specimens from five patients who had dry eye as part of the symptoms of chronic GVHD were examined by immunohistochemistry and transmission electron microscopy. Lacrimal gland specimens from five patients with Sjögren's syndrome (SS) were used as control samples. RESULTS: Lymphocytes, predominantly T cells, were found primarily in the periductal areas of the lacrimal gland from patients with chronic GVHD, whereas B cells were the dominant infiltrating cells in the acinar areas of the lacrimal gland from patients with SS. Notable findings in the lacrimal gland from patients with chronic GVHD were marked fibrosis of the glandular interstitium and an increase in the number of CD34(+) stromal fibroblasts. These findings were more prominent in patients with severe dry eye than in those with mild dry eye. Electron microscopic observations of the lacrimal gland from patients with chronic GVHD revealed that stromal fibroblasts were attached to various inflammatory cells, especially T cells, through primitive or rudimentary contacts. In addition, the presence of a well-developed rough endoplasmic reticulum in the fibroblasts and newly synthesized collagen fibrils in the extracellular matrix indicated an active production of extracellular matrix components. Electron micrographs revealed multilayered and thickened basal laminae of blood vessels, ducts, and lobules in the lacrimal gland of patients with chronic GVHD; however, these observations were infrequently observed in the lacrimal glands of patients with SS. CONCLUSIONS: The results suggest substantial differences in the lacrimal gland histopathology of patients with chronic GVHD and SS. In addition, it is likely that stromal fibroblasts are actively involved in the pathogenic process of chronic GVHD in the lacrimal gland by producing excessive extracellular matrix components.

Androgen influence on the meibomian gland.

PURPOSE: The hypothesis in the study was that androgens control meibomian gland function, regulate the quality and/or quantity of lipids produced by this tissue, and promote the formation of the tear film's lipid layer. To test this hypothesis, a study was conducted to determine whether androgen receptor protein exists in the epithelial cell nuclei of rat meibomian glands and, in addition, whether androgen deficiency and/or treatment influences the gross morphology, neutral lipid content, and fatty acid profile of the rabbit meibomian gland, as well as the appearance of the tear film lipid layer. METHODS: Rat lids were obtained and processed for immunohistochemistry. Meibomian glands from intact, androgen- and/or placebo-treated rabbits were analyzed by histology, and glandular lipids were evaluated by gas chromatography, high-performance liquid chromatography (HPLC), and mass spectrometry. The rabbit tear film lipid layer was assessed by interferometry. RESULTS: In the current study androgen receptor protein existed within acinar epithelial cell nuclei of rat meibomian glands; androgen deficiency was associated with alterations in the lipid content of the rabbit meibomian gland; 19-nortestosterone treatment modulated the fatty acid profile in the total and neutral lipid fractions of the rabbit meibomian gland; and androgens did not appear to influence the gross morphology of meibomian tissue or to exert a demonstrable effect on the rabbit tear film lipid layer. CONCLUSIONS: The findings show that the meibomian gland is an androgen target organ and that androgens influence the lipid profile within this tissue. However, the extent to which androgens regulate the production of these lipids and whether this action may impact tear film stability remain to be determined.

A reverse flow-metabolism mismatch pattern: a new marker of viable myocardium with greater contractility during dobutamine stress than myocardium with a flow-metabolism mismatch pattern.

Few studies have investigated the contractility of myocardium with a reverse flow-metabolism pattern; that is, greater uptake of nitrogen- 13-ammonia (NH3) than fluorine- 18-fluorodeoxyglucose (FDG) on positron emission tomography (PET). This study examined the contraction thickening represented by count increase in ECG-gated FDG-PET of myocardium with a reverse flow-metabolism pattern during low-dose dobutamine stress. Fifty-four patients with myocardial infarction were studied. Relative NH3 and FDG uptake (%NH3, %FDG) and %count increase were measured in 216 apical and 216 lateral segments on ECG-gated FDG-PET. The %count increase during low-dose dobutamine stress was greater in myocardium with a reverse flow-metabolism mismatch pattern than in myocardium with a flow-metabolism mismatch pattern (35.9+/-25.7% vs 24.6+/-15.9%, p=0.0221 in apical segments, and 38.4+/-22.6% vs 27.6+/-18.4%, p=0.0040 in lateral segments) despite smaller %FDG. A reverse flow-metabolism mismatch pattern should be noted as a new marker of viable myocardium with greater contractility during dobutamine stress than myocardium with a flow-metabolism mismatch pattern.