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.

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.

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.

Effects of bretylium tosylate on inhomogeneity of refractoriness and ventricular fibrillation threshold in canine hearts with quinidine-induced long QT interval.

We studied effects of bretylium tosylate (6 mg X kg-1, injected intravenously over 60s) on ventricular refractoriness and its inhomogeneity, and ventricular fibrillation threshold (VFT) in canine hearts with quinidine-induced long QT interval. In 3 anaesthetised open chest dogs, 30 mg X kg-1 of quinidine sulphate was injected intravenously over 5 min to produce QT prolongation. Effective refractory period (ERP) was determined at 8 test points of the right ventricle using extrastimuli. Temporal dispersion as an expression of inhomogeneity of ventricular refractoriness was estimated as the difference between the longest and the shortest ERP. VFT was determined using a train of pulses, 4 ms in duration and at 10 ms intervals. Effects of bretylium were determined from 30 to 60 min after injection. Quinidine-induced long QT interval did not change after bretylium (358 +/- 37 vs 348 +/- 26 ms) when transiently elevated blood pressure returned to the pre-bretylium level. Bretylium shortened ERP slightly (278 +/- 16 vs 268 +/- 14 ms, p less than 0.02) but did not shorten ERP after premature depolarisation (209 +/- 14 vs 209 +/- 15). However, temporal dispersion was significantly decreased by bretylium. VFT, which was lowered by quinidine (14.5 +/- 5.0 vs 8.5 +/- 2.9 mA, p less than 0.01), was elevated significantly by bretylium (21.9 +/- 6.9, p less than 0.001). These effects of bretylium might be attributed to the combination of its direct electrophysiology and indirect adrenergic actions.

Inhomogeneity of ventricular refractory period in canine heart with quinidine-induced long QT interval: a comparative study on effects of heart rate, isoprenaline, and lignocaine.

In anaesthetised open chest dogs, 30 mg . kg-1 of quinidine sulphate was injected intravenously over 5 min to produce QT prolongation. The sinus node was crushed. Effective refractory period (ERP) was determined at eight test points of the right ventricle using extra-stimuli after every seven basic ventricular pacings. Stimuli were of 2 ms duration and 1.5 times diastolic threshold. Temporal dispersion was estimated as the difference between the maximum and the minimum ERP of eight test points. Cycle lengths of basic ventricular drive were 700, 600, 500, and 400 ms. Time course of changes in ERP and its temporal dispersion was tested in five dogs. The effect of a 2 mg . kg-1 bolus injection followed by 70 micrograms . kg-1 . min-1 drip infusion lignocaine, on quinidine-induced changes in ERP was studied in eight dogs, and that of a 0.06 microgram . kg-1 . min-1 infusion of isoprenaline, was tested in six dogs. ERP was significantly prolonged after quinidine injection (220 +/- 20 vs 258 +/- 25 ms n = 19, basic cycle length = 500 ms, p less than 0.001). Temporal dispersion was also increased after quinidine (18 +/- 9 vs 33 +/- 12 ms n = 19, basic cycle length = 500 ms, p less than 0.001). With shortening of basic cycle length (BCL), ERPs were shortened significantly. Temporal dispersion, however, did not change. Lignocaine prolonged ERP even further (250 +/- 25 vs 273 +/- 16 ms BCL = 500 ms, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of candesartan and cilazapril on rats with myocardial infarction assessed by echocardiography.

The purpose of this study was to compare the angiotensin II type 1 receptor antagonist candesartan cilexitil (candesartan) and the angiotensin-converting enzyme inhibitor cilazapril on cardiac function, assessed by Doppler echocardiography and cardiac gene expression associated with cardiac remodeling, in rats with myocardial infarction. Candesartan or cilazapril was administered after myocardial infarction. At 1 and 4 weeks after myocardial infarction, cardiac function and mRNA expression in noninfarcted myocardium were analyzed. Candesartan and cilazapril equally prevented increases in hypertrophy in noninfarcted myocardium, left ventricular dilatation, and ejection fraction at 4 weeks. The E-wave/A-wave velocity ratio and the rate of E-wave deceleration, measures of diastolic function, increased to 9.2+/-0.6 and 26.3+/-2. 6 m/s2 at 1 week after myocardial infarction. Candesartan and cilazapril, administered at a dose of 1 mg/kg per day, prevented increases in E-wave/A-wave velocity ratio and E-wave deceleration at 1 and 4 weeks. Candesartan and cilazapril significantly suppressed increased mRNA expression of beta-myosin heavy chain, alpha-skeletal actin, and atrial natriuretic peptide in noninfarcted ventricle at 1 and 4 weeks and expression of collagen I and III at 4 weeks to a similar extent. When given at a dose of 10 mg/kg per day, both candesartan and cilazapril prevented cardiac dysfunction and gene expression to the same extent as when given at 1 mg/kg per day. In conclusion, Doppler echocardiography showed that candesartan and cilazapril equally improved systolic and diastolic function and that ventricular remodeling accompanied modulation of cardiac gene expression.

Brain natriuretic peptide as a cardiac hormone in essential hypertension.

PURPOSE: A natriuretic peptide, brain natriuretic peptide (BNP), has been isolated from porcine hearts. We performed this study to determine if BNP is secreted from the heart and to identify changes, if any, in the plasma BNP concentration in essential hypertension. PATIENTS AND METHODS: We measured the immunoreactive (ir) BNP concentration at intracardiac sites including the coronary sinus of five patients with heart disease during cardiac catheterization. We examined plasma ir-BNP in 48 hypertensive patients, 15 borderline hypertensive patients, and 25 normotensive subjects. RESULTS: Plasma ir-BNP in the coronary sinus was greater than at other cardiac sites. The concentration was significantly higher in hypertensive subjects than in borderline hypertensive or normotensive subjects. Hypertensive patients with left ventricular hypertrophy (LVH) established by echocardiography had higher plasma ir-BNP levels than those without LVH. In the hypertensive group, plasma ir-BNP was closely correlated with the LV mass index. In these patients, BNP levels were correlated with mean arterial pressure and inversely correlated with the LV ejection fraction, although these correlations were weak. Reverse-phase high-pressure liquid chromatography showed that the major component of circulating ir-BNP in the hypertensive and normotensive subjects corresponded to authentic human BNP-32. CONCLUSIONS: Human BNP-32 was secreted through the coronary sinus from the heart and may act as a cardiac hormone. Plasma BNP was increased in many of the hypertensive subjects with LVH. The increase in BNP seemed to be related to LVH or the cardiac overload associated with LVH.

Effects of preinfarction angina on myocardial injury in patients with acute myocardial infarction: a study with resting 123I-BMIPP and 201T1 myocardial SPECT.

METHODS: Recent studies have suggested that patients with preinfarction angina have smaller infarcts and a better in-hospital outcome than those without angina. The mechanisms responsible for limitation of infarct size in the presence of preinfarction angina are unclear. We examined the effects of preinfarction angina on myocardial injury in patients with the first acute myocardial infarction with resting 123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) 201TI myocardial scanning performed within 1 mo of infarction. RESULTS: Of 136 patients tested, 48 (35%) had preinfarction angina within 72 h before infarction, whereas 88 (65%) did not. BMIPP and 201TI defects were scored in 9 segments of the left ventricle (0 = normal, 1 = mild defect, 2 = moderate defect, 3 = severe defect, and 4 = no uptake). The total defect score was defined as the sum of the defect scores. There was no significant difference in percentage diameters of stenoses of infarct-related arteries, collateral circulation, total defect scores for BMIPP, or 201TI between the groups with and without preinfarction angina. However, the ratio of total defect score for 201TI to that for BMIPP was significantly smaller for patients with than for those without preinfarction angina (0.64 +/- 0.21 versus 0.74 +/- 0.25, respectively; P = 0.007). CONCLUSION: Preinfarction angina did not affect the areas at risk in acute myocardial infarction, as shown by BMIPP defect, but decreased necrotic myocardium in the areas at risk, as shown by 201TI defect, and increased metabolically damaged but viable myocardium, as shown by BMIPP and 201TI mismatch through unidentified mechanisms other than collateral circulation (e.g., ischemic preconditioning).

Does androgen insufficiency cause lacrimal gland inflammation and aqueous tear deficiency?

PURPOSE: The current investigators have shown that androgen treatment suppresses inflammation and stimulates the function of lacrimal glands in mouse models of Sjögren's syndrome. Recently, others have hypothesized that androgen insufficiency induces an autoimmune process in lacrimal tissue, leading to inflammation, a Sjögren's syndrome-like pathology, and aqueous tear deficiency. The purpose of the present study was to test this hypothesis. METHODS: Lacrimal glands were obtained from adult testicular feminized (Tfm) and control mice; castrated rats, guinea pigs, and rabbits; and castrated rats without anterior or whole pituitary glands and were processed for histology and image analysis. Tear volumes were measured in mice, in patients taking antiandrogen medications, and in age-matched human control subjects. RESULTS: Tfm mice, which are completely resistant to classical androgen action, did not have increased lymphocyte infiltration in their lacrimal glands or decreased tear volumes. No inflammation was evident in lacrimal tissues of male or female rats, guinea pigs, or rabbits 12 to 31 days after castration, no inflammation existed in rat lacrimal glands 15 to 31 days after orchiectomy and pituitary removal, and no aqueous tear deficiency was apparent in patients receiving antiandrogen therapy. CONCLUSIONS: Androgen deficiency may promote the progression of Sjögren's syndrome and its associated lacrimal gland inflammation, meibomian gland dysfunction, and severe dry eye. However, androgen insufficiency alone does not cause lacrimal gland inflammation, a Sjögren's syndrome-like pathology in lacrimal tissue, or aqueous tear deficiency in nonautoimmune animals and humans.

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.

Evaluation of antifibrillatory effects of drugs.

Several electrical stimulation techniques have been used to measure ventricular fibrillation (VF) threshold such as single pulse stimulation, train of pulses stimulation, continuous 50-Hz stimulation and sequential pulse stimulation. This study was undertaken to clarify the difference in VF threshold values obtained by each method. The development of VF was classified into 4 stages. Stage 1 is the phase in which fragmented activities are generated at the stimulated area of the ventricular muscle. In stage 2, the local activities propagate to surrounding ventricular muscle, causing ventricular excitation. Stage 3 is characterized by repetitive ventricular excitations. In state 4, repetitive ventricular responses in a form of accelerating tachycardia induce disorganized excitations that finally degenerate into fibrillation. Based on this classification of stages between local excitation and fibrillation, single pulse stimulation is considered to measure VF threshold for stages 1 to 4, continuous 50-Hz stimulation for stages 2 to 4 and sequential pulse stimulation for stages 3 and 4. Thus, the antifibrillatory effect of drugs can be interpreted with some significance by using different stimulation methods. The sequential pulse stimulation method revealed that some antiarrhythmic agents caused a dissociation between repetitive nonstimulated excitation (RE) threshold and VF threshold. Procainamide and disopyramide increased RE threshold while decreasing VF threshold. Mexiletine and lidocaine elevated both RE and VF thresholds. Local infusion of procainamide at the site of test stimulation reduced both thresholds. However, after the application of procainamide to the whole heart, RE threshold remained decreased but VF threshold was elevated. It is likely that the antifibrillatory effect of the drug includes 2 different processes: antireentrant and antimultiple reentrant effects.

Tear function index. A new measure of dry eye.

OBJECTIVE: To develop an efficient way to evaluate tear dynamics clinically. PARTICIPANTS: Three hundred fifty-two patients with dry eye, 64 of whom had Sjögren syndrome, and 55 normal subjects. DESIGN: Because various forces that affect tear drainage are reflected in the values of the Schirmer test with anesthesia and the tear clearance rate, we introduced a new measure of tear dynamics, the tear function index, which is the value obtained from dividing the value of the Schirmer test with anesthesia by the tear clearance rate. RESULTS: The tear function index was more specific (91.8%) and sensitive (78.9%) in diagnosing dry eye associated with Sjögren syndrome than was the Schirmer or tear clearance rate test alone. Tear function indexes below 96 were consistent with dry eye and those below 34 were seen primarily in patients with Sjögren syndrome. CONCLUSIONS: The tear function index offers a new method to evaluate tear production with the Schirmer test, introduces an extended way to measure tear flow combining with tear drainage, and gives a practical measure to diagnose dry eye.

Gender- and androgen-related influence on the expression of proto-oncogene and apoptotic factor mRNAs in lacrimal glands of autoimmune and non-autoimmune mice.

Our previous studies have shown that the mRNA levels of c-myb, c-myc, bcl-2 and p53 are higher, and partial Fas antigen (i.e. exons 1-2) lower, in lacrimal tissues of female, as compared to male, MRL/lpr mice, which are a model of Sjögren's syndrome. We have also found that this gender-related difference in bcl-2 and c-myb expression appears to be due to the influence of androgens. To extend these findings, we sought to determine: first, whether these gender- and/or hormone-associated variations in mRNA content are unique to MRL/lpr mice, or are also present in lacrimal glands of other murine strains, including autoimmune NZB/NZW F1 (F1) and non-obese diabetic (NOD), as well as non-autoimmune C3H/HeJ (C3H) and BALB/c, mice; and second, whether the levels of these apoptotic factor mRNAs are altered in lacrimal tissues of mice (i.e. testicular feminized (Tfm) with dysfunctional androgen receptors, as compared to glandular amounts in their 'normal' controls (i.e. Tabby). Lacrimal tissues were obtained from adult mice, which were either untreated or treated with placebo or testosterone for 21 days. Glands were processed for the analysis of proto-oncogene mRNAs by RT-PCR (at exponential phase of amplification) and data were standardized to the corresponding levels of beta-actin mRNA. Our results demonstrate that Fas antigen, Fas ligand, c-myb, c-myc, bcl-2, Bax and p53 mRNAs are present in lacrimal tissues of F1, NOD, C3H, BALB/c, Tabby and Tfm mice. The relative levels of Fas antigen mRNA are consistently higher in glands of males, whereas amounts of bcl-2 mRNA are greater in tissues of F1, C3H and BALB/c females. Testosterone administration induced a significant increase in the lacrimal gland content of Bax mRNA, but a striking decrease in the lacrimal tissue level of bcl-2 mRNA in F1 and C3H mice. Lacrimal glands of Tfm mice contained elevated amounts of bcl-2 mRNA, as compared to values in tissues of their Tabby controls. In summary, our findings show that fundamental gender-related differences exist in the expression of genes associated with programmed cell death in lacrimal glands of autoimmune and normal mice. In addition, some of these differences may be due, at least in part, to the effect of androgens.

Androgens and dry eye in Sjögren's syndrome.

Sjögren's syndrome is an extremely complex and currently incurable autoimmune disorder, which occurs primarily in females, and is associated with lacrimal gland inflammation, meibomian gland dysfunction, and severe dry eye. We hypothesize that androgen deficiency, which reportedly occurs in primary and secondary Sjögren's syndrome (e.g., systemic lupus erythematosus, rheumatoid arthritis), is a critical etiologic factor in the pathogenesis of dry eye syndromes. We further hypothesize that androgen treatment to the ocular surface will promote both lacrimal and meibomian gland function and alleviate both "aqueous-deficient" and "evaporative" dry eye. Our results demonstrate that androgens regulate both lacrimal and meibomian gland function, and suggest that topical androgen administration may serve as a safe and effective therapy for the treatment of dry eye in Sjögren's syndrome.

Circulating immunoreactive endothelin in patients undergoing percutaneous transluminal coronary angioplasty.

Circulating immunoreactive endothelin (ir-ET) in the coronary sinus (CS) and the femoral artery (Ao) was measured in patients who underwent percutaneous transluminal coronary angioplasty (PTCA). Plasma ir-ET level in the CS was significantly increased from 1.6 +/- 0.8 pg/mL to 2.0 +/- 1.0 pg/mL after PTCA (P less than .05). Plasma ir-ET level in the Ao tended to increase after PTCA, but it was not significant. Plasma ir-ET level in the CS was not related to the plasma thromboglobulin level, plasma thrombin-antithrombin complex level, mean blood pressure, or heart rate. These results suggest that the increase of plasma ir-ET level in the CS may be associated with the coronary endothelial injury by PTCA.

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.

Increased comfort and decreased inflammation of the eye by cooling after cataract surgery.

PURPOSE: Cooling can reduce clinical symptoms and pain caused by traumatic swelling or fracture of extremities. We obtained subjective and objective measures of the effects of cooling of the eyes after cataract surgery. METHODS: Twenty patients with bilateral cataracts were enrolled in this study. For each patient, an ice-cold eye mask was applied over gauze to one operated-on eye for two hours after the operation and was not applied after operation on the other eye. After each operation, the patient rated comfort on a five-point scale. The severity of inflammation associated with each procedure was evaluated by using an infrared radiation thermometer to determine the central corneal temperature and a laser flare-cell meter to determine the cell and flare count, at intervals up to 28 days after surgery. RESULTS: Cooling, applied after the first operation in ten patients and after the second operation in ten patients, statistically significantly increased the patients' comfort level and was associated with a significant decrease in central corneal temperature on days 0, 1, and 3; in cell counts on days 1, 3, 7, and 14; and in flare counts on days 1, 14, and 28. CONCLUSIONS: Cooling increased the comfort level and reduced inflammation after cataract surgery, with no adverse effects.