Non-Infectious Dermatological Manifestations among Patients with Diabetes Mellitus in Basrah, Iraq.

Diabetes mellitus (DM) is a clinical illness usually linked to a wide range of skin manifestations; however, skin, as the greatest organ in the body, has received little attention. As a result, this study aimed to detect the prevalence and pattern of non-infectious skin disorders among patients with diabetes. This study was carried out at the Faiha Specialized Diabetes, Endocrine, and Metabolism Center, Basrah Province, Iraq, from September 2020 to September 2021. The data were collected from 347 patients with Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM). The exclusion criteria were patients with skin changes due to some medications, pregnancy, iatrogenic factors, skin infections, established hypo- or hyper-thyroidism, Cushing or adrenal insufficiency, pituitary disorders, end-stage renal impairment, malignancy, and established rheumatological disease and those who were on chemotherapy. Full dermatological examinations and screenings were performed under the supervision of a dermatologist expert and all clinically definable cutaneous lesions were recorded. The prevalence of skin lesions was estimated at 71.5% in patients. Pruritus, xerosis, acrochordon, diabetic dermopathy, acanthosis nigricans, and insulin-related lipohypertrophy were the commonest skin lesions reported among the patients. The occurrence of skin lesions in diabetic patients was proportional to the female gender, duration of disease, obesity, insulin therapy, and worse glycemic control. There was a broad spectrum of skin lesions in both T1DM and T2DM with corresponding prevalence.

Experimental Demonstration of Hadron Beam Cooling Using Radio-Frequency Accelerated Electron Bunches.

Cooling of beams of gold ions using electron bunches accelerated with radio-frequency systems was recently experimentally demonstrated in the Relativistic Heavy Ion Collider at Brookhaven National Laboratory. Such an approach is new and opens the possibility of using this technique at higher energies than possible with electrostatic acceleration of electron beams. The challenges of this approach include generation of electron beams suitable for cooling, delivery of electron bunches of the required quality to the cooling sections without degradation of beam angular divergence and energy spread, achieving the required small angles between electron and ion trajectories in the cooling sections, precise velocity matching between the two beams, high-current operation of the electron accelerator, as well as several physics effects related to bunched-beam cooling. Here we report on the first demonstration of cooling hadron beams using this new approach.

A human specific Alu DNA cassette is found flanking the genes of transcription factor AP2.

OBJECTIVE: Alu elements are retroposons that invaded the primate genome and shaped its biology. Some Alus inserted recently and are polymorphic in the human population. It is these Alus that are being sought after in disease association studies and regulatory biology. Discovering polymorphic Alus in the human genome can open areas of new research in these fields. RESULTS: Using the polymerase chain reaction on genomic DNA, we identified a polymorphic Alu in the flanking region of the TFAP2B and TFAP2D genes. The new insert was found in higher frequency in Europeans (0.4) and Asians (0.38) and lower frequency in Africans (0.25). We also show this Alu to be part of a 3 Alu cassette that is human specific. The TFAP2B and TFAP2D genes encode members of the transcription factor AP-2, which plays a role in organ development. The insertion of this Alu cassette flanking the transcription factor genes distinguishes humans from the primates. This cassette can possibly affect the regulation of both genes or alternately provoke genomic deletions, which we have shown in this study. Its presence in such a location is intriguing and unquestionably opens an investigational window in disease association studies and in the field of gene regulation.

[Cardiac rehabilitation in elderly patient]. / Réadaptation cardiaque du sujet âgé.

According to "OMS" we are old at age 65. Because of the ageing population (life expectancy has increased in Europe) and medical progress, more and more old patients are addressed to cardiac rehabilitation centers. Ageing is a physiological process which varies between individuals, and in the same person organ ageing also differs. Old patient has usually several pathological diseases. Because old patient has restricted functional reserve, acute illness could get him closer to the decompensation area. Complications are more frequent in ageing people, and often need a specific initial treatment which delays rehabilitation. Rehabilitation program of old non-disabled patient is not different from that addressed to youngers. The main objective for dependent people is to restore the ability to perform activities of daily living. Correction of vascular risk factors and therapeutic education are also valuable in elderly. For patients with difficulty to remember or to understand instructions, family help is valuable when possible. The benefit of the rehabilitation in the elderly is demonstrated by several studies.

Effectiveness of the critical congenital heart disease screening program for early diagnosis of cardiac abnormalities in newborn infants.

OBJECTIVES: To evaluate the effectiveness of critical congenital heart disease (CCHD) screening program for early diagnosis of cardiac anomalies in newborn infants.  Methods: This is a hospital-based prospective cross-sectional study conducted in the Pediatric and Neonatology Department, King Fahad Hospital at  Albaha, Saudi Arabia, between February 2016 and February 2017. Results: We screened 2961 (95.4%) of 3103 patients in a nursery unit; 142 (4.6%) patients were not screened. The test was positive in 114 (3.9%) patients and negative in 2847 (96.1%). There were 94 (3.2%) false positives and 20 (0.7%) true positives. Critical cardiac defects were diagnosed in 7 (0.2%) patients of all screened infants, and severe pulmonary hypertension was diagnosed in 13 (0.4%) patients. True negative results were found in 2841(96%) patients, and no cardiac defect was diagnosed, whereas false negative results were seen in 6 (0.2%) patients diagnosed with ventricular septal defect. The sensitivity was 77%, and the specificity was very high at 97%, with a positive predictive value of 18%, and a negative predictive value of 99.8% (95% confidence interval 13.78-19.18, p=0.0001). Conclusion: Pulse oximetry was found to be easy, safe, sensitive, and highly specific for diagnosis of CCHD.

Follicular fluid PlGF/sFlt-1 ratio and soluble receptor for advanced glycation end-products correlate with ovarian sensitivity index in women undergoing A.R.T.

PURPOSE: Considering potential roles of soluble receptor for advanced glycation end products (sRAGE) and placental growth factor (PlGF) in ovarian function and embryo implantation, in the present study we have evaluated the association of these factors and also PlGF/sFlt-1 ratio with the ovarian response and implantation rate by dividing patients according to the OSI. METHODS: In a cross-sectional study, 90 infertile women who were undergoing ICSI cycle using long protocol were recruited. The patients were divided according to ovarian sensitivity index (OSI). ICSI cycle outcomes were evaluated for each patient and PlGF, sFlt-1 and sRAGE levels of follicular fluid were assayed using commercial ELISA kits. RESULTS: Follicular fluid (FF) sRAGE levels and PlGF/sFlt-1 ratio were statistically greater in high-responder women than other responders (p < 0.05). Positive correlations were obtained between sRAGE level with the number of oocytes, follicles and OSI level. sRAGE levels with cutoff value of 4.83 (ng/ml) for evaluating the pregnancy outcome showed 81.8 % sensitivity and 60.7 % specificity. Furthermore, there were positive associations between PlGF/sFlt-1 ratio with the number of oocytes, embryos and OSI level. CONCLUSION: In conclusion, the results of current study supported that good ovarian response is independent of pregnancy outcome. Our results showed that FF levels of sRAGE and PlGF/sFlt-1 ratio could be used as markers for determining the high-responder women. Also, FF sRAGE levels could be a good predictor for ART outcome.

Intrauterine administration of hCG immediately after oocyte retrieval and the outcome of ICSI: a randomized controlled trial.

STUDY QUESTION: Does the intrauterine administration of hCG immediately after oocyte retrieval in antagonist cycles with ICSI and fresh embryo transfer (ET) influence the implantation rate or chemical and clinical pregnancy rates? SUMMARY ANSWER: The intrauterine administration of hCG after oocyte retrieval increases the implantation rate and chemical and clinical pregnancy rates. WHAT IS KNOWN ALREADY: Over half of IVF/ICSI cycles fail due to implantation failure. Intrauterine administration of hCG, a few minutes before ET, increased the implantation and pregnancy rates in most but not in all studies. The effect of intrauterine administration of hCG, after oocyte retrieval, has not yet been studied. STUDY DESIGN, SIZE, DURATION: The study was a parallel, triple-blind randomized clinical trial (RCT) performed from September 2015 to February 2016, in a university hospital. We recruited women undergoing antagonist ovarian stimulation, ICSI and ET. For an effect size of 0.2, power of 80% at a significance level of 0.05, we needed 150 participants. Accounting for a 7% dropout rate, a total of 160 women was considered appropriate. A computer-generated randomization list with a block size of 4, with 1:1 allocation was used. The treatment allocation was placed in a sealed, opaque, envelope and picked up consecutively. Immediately after oocyte retrieval, patients in the intervention and control groups were treated with intrauterine injection of hCG and saline, respectively. Participants underwent ET on Day 3. A beta-hCG test was done at 2 weeks. If positive, three transvaginal-ultrasonographies (TVSs) were done at 3, 4 and 10 weeks after ET. The participants were called up thereafter and questioned about the continuity of their pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHOD: Of 1990 women attending the infertility clinic of our university hospital, 508 were IVF/ICSI candidates during the study period, and 245 of the patients on an antagonist cycle met the criteria to be invited into our trial. Inclusion criteria were normal ovarian reserve, age ≤41, undergoing ICSI, and fresh ET and normal TSH and prolactin. Uncontrolled chronic disease, severe hydrosalpinx, severe endometriosis, morphologic embryo deficiencies, non-obstructive azospermia and high risk of severe ovarian hyperstimulation syndrome were criteria for exclusion. After taking an informed consent, a total of 158 participants were recruited, of which 80 were randomly allocated to receive intrauterine 500 IU hCG in up to 0.5 ml normal saline and 78 to receive intrauterine 0.5 ml normal saline immediately after oocyte retrieval, during general anaesthesia. ICSI was performed conventionally. The 4-8 cell embryos were transferred on the third day after oocyte retrieval. Implantation rate, chemical and clinical pregnancy rates were analysed and compared between the two groups. MAIN RESULTS AND THE ROLE OF CHANCE: Patients' demographic and baseline characteristics were comparable. The clinical results showed statistically significant differences between the two groups regarding the biochemical pregnancy rate (59.2 versus 31.3%; P = 0.001; odds ratio (OR) = 1.88; 95% CI, 1.26-2.82; risk difference (RD) = 27.8; 95% CI, 11.2-42.3), implantation rate (37 versus 17%; P = 0.012; OR = 2.29; 95% CI, 1.02-5.14; RD = 20.2; 95% CI, 5.4-33.8), clinical pregnancy rate (50.7 versus 16.4%; P < 0.001; OR = 3.08; 95% CI, 1.71-5.55; RD = 34.3; 95% CI, 18.7-47.6) and ongoing pregnancy rate (40.1 versus 13.4%; P = 0.001; OR = 3.04; 95% CI, 1.55-5.93; RD = 27.4; 95% CI, 12.7-40.6). The abortion and ectopic pregnancy rates were not statistically different between the two groups. LIMITATIONS, REASONS FOR CAUTION: The insertion of an intrauterine insemination catheter and the injection of a small amount of saline into the uterine cavity (without hCG) may also have some impact on implantation. This effect could be studied by comparing this intervention with another study group without any intrauterine injection.There are no specific side effects mentioned in the literature for the intrauterine administration of hCG, neither were any observed in our study, but it is best to be cautious about probable side effects, because this type of intervention is relatively new and experimental, and deserves more studies before being entered into routine clinical practice. WIDER IMPLICATIONS OF THE FINDINGS: Intrauterine administration of hCG immediately after oocyte pick up increases its effectiveness; however, further investigations are required before this procedure can be recommended for clinical practice. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Women's Health Research Center, Tabriz University of Medical Sciences, Iran. No external funds were used. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: IRCT201206165485N4. TRIAL REGISTRATION DATE: 2 September 2015. DATE OF FIRST PATIENT'S ENROLMENT: 2 September 2015.

Circulating Cell-free miRNA Expression and its Association with Clinicopathologic Features in Inflammatory and Non- Inflammatory Breast Cancer.

Recent discovery showing the presence of microRNAs (miRNAs) in the circulation sparked interest in their use as potential biomarkers. Our previous studies showed the diagnostic potential of miR-451 as a serological marker for inflammatory breast cancer (IBC), miR-337- 5p and miR-30b for non-inflammatory breast cancer (non-IBC). The aim of this study is to investigate the prognostic values of circulating miRNAs by comparing the amounts of 12 circulating miRNAs in the serum of IBC and non-IBC from Tunisian breast cancer patients, and by determinating whether correlated pairs of miRNAs could provide useful information in the diagnosis of IBC and non-IBC patients. TaqMan qPCR was performed to detect circulating expression of miRNAs in serum of 20 IBC, 20 non-IBC and 20 healthy controls. Nonparametric rank Spearman rho correlation coefficient was used to examine the prognostic value of miRNAs and to assess the correlation profile between miRNAs expression. Further, a large number of miRNAs were highly correlated (rho>0.5) in both patients groups and controls. Also, the correlations profiles were different between IBC, non-IBC and healthy controls indicating important changes in molecular pathways in cancer cells. Our results showed that miR-335 was significantly overexpressed in premenopausal non-IBC patients; miR-24 was significantly overexpressed in non-IBC postmenopausal patients. Patients with previous parity had higher serum of miR-342-5p levels than those without. Furthermore, patients with HER2+ IBC present lower serum levels of miR-15a than patients with HER2- disease. Together, these results underline the potential of miRNAs to function as diagnostic and prognostic markers for IBC and non-IBC, with links to the menopausal state, Her2 status and parity.

[Neonatal liver abscess after umbilical venous catheter]. / Abcès hépatique néonatal lié à un cathéter veineux ombilical.

INTRODUCTION: The use of an umbilical venous catheter (UVC) is common practice in neonatal units and is subjected to strict rules of insertion and monitoring to detect potential complications. Hepatic abscess is one of these rare complications. OBSERVATION: We report the observation of a 15-day-old female newborn admitted for a hepatic abscess. The patient had been hospitalized at birth in a neonatal intensive care unit. With the appearance of hemodynamic instability on the 4th day of life, a nosocomial infection was suspected and was treated with ceftazidime, vancomycin and amikacin. Later, as the need for O(2) increased and plasma C-reactive protein (CRP) was 190 mg/L, the patient received imipenem and vancomycin, while an abdominal ultrasound examination showed a hepatic abscess. A triple antibiotic treatment was initiated with imipenem, vancomycin, and metronidazole, while the initial examination showed a clinically stable patient with a CRP at 208 mg/L. Abdominal ultrasounds showed a hepatic abscess measuring 53.4×24.9 mm on day 21 and 51.4 mg/L CRP. Then the abscess dimensions decreased to 35.7×14 mm. The antibiotic therapy was maintained for 4 weeks. CONCLUSION: Hepatic abscess should be suspected in neonates with UVC with sepsis and persistent signs of inflammation in spite of adequate antibiotic treatment.

Evaluation of intralesional 0.2% ciprofloxacin as a treatment for cutaneous leishmaniasis.

Although cutaneous leishmaniasis lesions usually heal spontaneously they cause unsightly scarring. This study evaluated a possible new therapy in 38 patients, with 70 lesions, randomly assigned to intralesional injection of ciprofloxacin (0.2%) or intralesional sodium chloride hypertonic solution (7%). After excluding patients who defaulted on treatment, lesions assigned to sodium chloride treatment (n = 21) were completely healed (with or without scarring) in 76.2% of cases, and, when a scar remained, the scar size was reduced 66.0% compared with the original lesion. Lesions assigned to ciprofloxacin (n = 27) showed an 81.5% healing rate with an average scar size reduction of 68.6%. Intralesional 0.2% ciprofloxacin was as effective as hypertonic saline in the treatment of cutaneous leishmaniasis infection.

Prediction of latency interval in preterm premature rupture of membranes using sonographic myometrial thickness.

Despite recent advances in perinatal care, Preterm Premature Rupture of Membranes (PPROM) continues to lead to important obstetric complications. This study was aimed to evaluate the role of sonographic measurement of myometrial thickness in prediction of latency interval in women with PPROM. This analytic- descriptive and case- control study was performed on pregnant women with PPROM presenting to Tabriz Al-Zahra Hospital since 2006 to 2008. Thirty pregnant women with PPROM and 30 pregnant women with normal pregnancy were enrolled. Mean gestational age was 30.60 +/- 1.99 week and in case and 31.13 +/- 20.01 week in control group (p = 0.307). Mean gravidity was 1.63 +/- 0.49 in case and 1.47 +/- 0.50 in control group (p = 0.210). Mean parity was 0.53 +/- 0.62 in case and 0.57 0.50 in control group (p = 0.819). Mean anterior myometrial thickness was 8.23 +/- 2.59 mm in case and 7.71 +/- 1.45 mm in control group (p = 0.344). Mean posterior myometrial thickness was 8.90 +/- 2.86 mm in case and 8.12 +/- 1.54 mm in control group (p = 0.197). Mean fundus myometrial thickness was 9.10 +/- 3.54 mm in case and 8.77 +/- 1.77 mm in control group (p = 0.648). Mean latency interval of women with PPROM was 18.70 +/- 20.68 day and mean sonography to labor interval was 57.30 +/- 16.14 day (p < 0.01). Mean latency interval of women with PPROM was significantly shorter than mean sonography to labor interval in control group patients (p < 0.05). In our study, 50% of women in 10 first days after PPRM labored and only 43.3% of women labored in 7 first days after PPROM. In this study, significant correlation was not found between myocardial sickness in anterior, posterior and fundus with latency interval.

Evaluation of intralesional 0.2% ciprofloxacin as a treatment for cutaneous leishmaniasis

Although cutaneous leishmaniasis lesions usually heal spontaneously they cause unsightly scarring. This study evaluated a possible new therapy in 38 patients, with 70 lesions, randomly assigned to intralesional injection of ciprofloxacin [0.2%] or intralesional sodium chloride hypertonic solution [7%]. After excluding patients who defaulted on treatment, lesions assigned to sodium chloride treatment [n = 21] were completely healed [with or without scarring] in 76.2% of cases, and, when a scar remained, the scar size was reduced 66.0% compared with the original lesion. Lesions assigned to ciprofloxacin [n = 27] showed an 81.5% healing rate with an average scar size reduction of 68.6%. Intralesional 0.2% ciprofloxacin was as effective as hypertonic saline in the treatment of cutaneous leishmaniasis infection

In vitro inhibition of Helicobacter pylori urease with non and semi fermented Camellia sinensis.

PURPOSE: Helicobacter pylori is the etiological agent in duodenal and peptic ulcers. The growing problem of antibiotic resistance by the organism demands the search for novel compounds, especially from natural sources. This study was conducted to evaluate the effect of Camellia sinensis extracts on the urease enzyme that is a major colonization factor for H. pylori. METHODS: Minimum inhibitory concentrations of nonfermented and semifermented C. sinensis methanol: water extracts were assessed by broth dilution method. Examination of the urease function was performed by Mc Laren method, and urease production was detected on 12% SDS polyacrylamide gel electrophoresis from whole cell and membrane bound proteins. RESULTS: Both extracts had inhibitory effects against H. pylori and urease production. At a concentration of 2.5 mg/ml of nonfermented extract and 3.5 mg/ml of semifermented extract the production of Ure A and Ure B subunits of the urease enzyme were inhibited completely. A concentration of 4 mg/ml of nonfermented and 5.5 mg/ml of semifermented extract were bactericidal for H. pylori. CONCLUSIONS: C. sinensis extracts, especially the nonfermented, could reduce H. pylori population and inhibit urease production at lower concentrations. The superior effect of nonfermented extract is due to its rich polyphenolic compounds and catechin contents.

Demystifying the ACE polymorphism: from genetics to biology.

The angiotensin converting enzyme (ACE) I/D polymorphism has been one of the most studied genetic systems. It comprises hundreds of reports and a myriad of disease associations, including cardiovascular, metabolic, immune, cancer, aging, neurodegenerative and psychiatric diseases. Despite the wealth of information on the ACE polymorphism and the well-known functions of ACE, several questions arise. Why does the ACE polymorphism associate with so many diseases? What is its function? In this review, we summarize the current information on the ACE polymorphism and explain its function in the context of cell survival. We also provide a model to understand its role in biology and disease at the organism and population levels.

Oleuropein, a non-toxic olive iridoid, is an anti-tumor agent and cytoskeleton disruptor.

Oleuropein, a non-toxic secoiridoid derived from the olive tree, is a powerful antioxidant and anti-angiogenic agent. Here, we show it to be a potent anti-cancer compound, directly disrupting actin filaments in cells and in a cell-free assay. Oleuropein inhibited the proliferation and migration of advanced-grade tumor cell lines in a dose-responsive manner. In a novel tube-disruption assay, Oleuropein irreversibly rounded cancer cells, preventing their replication, motility, and invasiveness; these effects were reversible in normal cells. When administered orally to mice that developed spontaneous tumors, Oleuropein completely regressed tumors in 9-12 days. When tumors were resected prior to complete regression, they lacked cohesiveness and had a crumbly consistency. No viable cells could be recovered from these tumors. These observations elevate Oleuropein from a non-toxic antioxidant into a potent anti-tumor agent with direct effects against tumor cells. Our data may also explain the cancer-protective effects of the olive-rich Mediterranean diet.

A genetic variant of ACE increases cell survival: a new paradigm for biology and disease.

The human angiotensin converting enzyme (ACE) polymorphism is caused by an Alu element insertion resulting in three genotypes (Alu+/+, Alu+/-, Alu-/-, or ACE-II, ACE-ID, and ACE-DD, respectively), with ACE-II displaying lower ACE activity. The polymorphism is associated with athletic performance, aging, and disease. Population studies, however, were confounding because variants of the polymorphism appeared to fortuitously correlate with health and various pathological states. To clarify the functional role of the polymorphism, we studied its direct effect on cell survival. ACE-II (Alu+/+) human endothelial cells (EC) had lower angiotensin-II levels and 20-fold increased viability after slow starvation as compared to ACE-DD cells (Alu-/-). By RT-PCR, only ACE-II cells expressed the pluripotent/stem cell-maintenance factors nanog, numb, and klotho. ACE inhibition by captopril in ACE-DD cells mimicked the ACE-II genotype. These results provide the first evidence of a functional role for a naturally occurring polymorphism, having broad implications for human biology, longevity, and disease.

ACE inhibition actively promotes cell survival by altering gene expression.

We tested the effect of ACE inhibition on the survival of bovine retinal (REC) and choroidal (CEC) endothelial cells (EC) in culture. The ACE inhibitor captopril delayed the apoptotic tube collapse of REC on Matrigel for >15 days. Captopril treatment of confluent monolayers (2-8 weeks) followed by slow starvation (2-4 weeks) increased EC viability by approximately 200%. Two-week captopril exposures were sufficient to confer maximal protection. Only vehicle-treated EC demonstrated apoptotic features such as membrane blebbing and DNA laddering. By RT-PCR, the starvation marker p202 was upregulated only in starved cells. In REC, captopril upregulated the pro-survival proteins mortalin-2, uPA, and uPAR while downregulating the anti-growth sprouty-4 and tPA. In CEC, captopril also upregulated tPA and its inhibitor PAI-1. Amiloride (uPA inhibitor) blocked the captopril-induced increase in EC survival, secondary sprouting, and invasion in Matrigel. The pro-survival effects of captopril involve the reprogramming of genes involved in cell survival and immortalization.

Age-related macular degeneration: a new viewpoint.

Age-related macular degeneration (AMD) is a major cause of blindness in the United States. AMD can be categorized into an atrophic (dry) form and a neovascular (wet, exudative) form. The atrophic form involves alterations of pigment distribution, loss of RPE cells and photoreceptors and diminished retinal function due to an overall atrophy of the cells. The neovascular AMD involves proliferation of abnormal choroidal vessels, which penetrate the Bruch's membrane and RPE layer into the subretinal space, thereby forming extensive clots and/or scars. Both environmental and genetic factors are suspected to play a role in AMD. Despite extensive genetic screening of candidate genes only two associations have been identified with AMD (Adenosine triphosphate (ATP)-binding cassette rim (ABCR) protein and apolipoprotein E gene-ApoE). The ABCR protein is retinal specific and accounts for only 3% of AMD cases. ApoE is not specific to the retina, and has been more intriguingly associated with Alzheimer's, another disease of age. The most consistent major risk factor in AMD is age. Our studies on the ACE gene show an association of protection with an Alu element insert, which might be affecting the level of the ACE gene. The ApoE 4 allele and the ACE Alu+/+ genotype have both been shown to be a risk for Alzheimer's and protective for AMD. Given these recent genetic associations, we should examine possible common pathways in diseases of age and their interaction with human genetic polymorphisms.

Alu DNA polymorphism in ACE gene is protective for age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. We report an association between an Alu polymorphism in the angiotensin-converting enzyme (ACE) gene with the dry/atrophic form of AMD. Using the polymerase chain reaction (PCR) on genomic DNA isolated from patients with AMD (n=173), and an age-matched control population (n=189), we amplified a region polymorphic for an Alu element insertion in the ACE gene. The Alu(+/+) genotype occurred 4.5 times more frequently in the control population than the dry/atrophic AMD patient population, (p=0.004). The predominance of the Alu(+/+) genotype within the unaffected control group represents a protective insertion with respect to the human ocular disease, dry/atrophic AMD. This is the first demonstration of an Alu element insertion exerting protective effects against a known human disease.

Effects of tenascin-C on normal and diabetic retinal endothelial cells in culture.

PURPOSE: Tenascin-C (TN-C) is expressed in embryogenesis, tissue remodeling, and healing. It is up-regulated in retinas of patients affected by diabetic retinopathy (DR). Because TN-C may promote neovascularization, its potential angiogenic effects were examined in vitro in normal and diabetic retinal endothelial cells (RECs). METHODS: Bovine and human RECs were cultured on plastic or reconstituted basement membrane (BM) matrix. Production of TN-C, capillary-like tube formation, secondary sprouting, and cell migration, survival, and proliferation were measured with or without angiogenic growth factors (GFs). Antibodies and inhibitors were used to determine the involvement of specific TN-C receptors and signaling pathways. RESULTS: TN-C significantly delayed collapse of REC capillary-like tubes on BM matrix. It decreased tube involution associated with serum deprivation, high glucose, and exposure to TGF-beta. TN-C's enhancement of tube stability was mediated by alphavbeta3 integrin. TN-C increased REC viability in 0.5% serum and stimulated REC proliferation in 10% serum. It promoted REC secondary sprouting on BM matrix, which involved signaling through mitogen-activated kinase kinase (MEK) and p38 mitogen-activated protein kinase. TN-C also enhanced tube branching after treatment with VEGF and stimulated REC migration twofold. Angiogenic GF increased TN-C production by RECs in an additive manner, which may explain higher levels of TN-C deposition in DR cells. CONCLUSIONS: TN-C was overexpressed in diabetic and DR REC cultures. TN-C enhanced the sprouting, migratory, and survival effects of angiogenic GFs, and had distinct proliferative, migratory, and protective capacities. The data suggest that TN-C may act as a proangiogenic mediator in DR and other pathologic conditions involving neovascularization.