Neglect of attention to reproductive health in women with HIV infection: contraceptive use and unintended pregnancies in the Swiss HIV Cohort Study.

OBJECTIVES: Women with HIV infection are mainly of reproductive age and need safe, effective and affordable contraception to avoid unintended pregnancies. The aim of this study was to evaluate contraceptive use and unintended pregnancies in this population in Switzerland. METHODS: A self-report anonymous questionnaire on contraceptive methods, adherence to them, and unintended pregnancies was completed by women included in the Swiss HIV Cohort Study (SHCS) between November 2013 and June 2014. Sociodemographic characteristics and information related to combined antiretroviral therapy and HIV disease status were obtained from the SHCS database. RESULTS: Of 462 women included, 164 (35.5%) reported not using any contraception. Among these, 65 (39.6%) reported being sexually active, although 29 (44.6%) were not planning a pregnancy. Of 298 women using contraception, the following methods were reported: condoms, 219 (73.5%); oral hormonal contraception, 32 (10.7%); and intrauterine devices, 28 (9.4%). Among all women on contraception, 32 (10.7%) reported using more than one contraceptive method and 48 (16%) had an unintended pregnancy while on contraception (18, condoms; 16, oral contraception; four, other methods). Of these, 68.1% terminated the pregnancy and almost half (43.7%) continued using the same contraceptive method after the event. CONCLUSIONS: Family planning needs in HIV-positive women are not fully addressed because male condoms remained the predominant reported contraceptive method, with a high rate of unintended pregnancies. It is of utmost importance to provide effective contraception such as long-acting reversible contraceptives for women living with HIV.

Mirage de tuberculose in the 21st century.

The occurrence of transient culture positivity for Mycobacterium tuberculosis (MTB), known as mirage de tuberculose, poses significant challenges in understanding its spectrum and implications. Here, we report a case of transient culture positivity, oscillating between detectable and non-detectable MTB cultures with minimal radiological features and review the literature on this phenomenon. The scarcity of scientific literature on this subject stems from the inherent impossibility of systematically studying mirage de tuberculose. Ethical and public health concerns prevent withholding treatment to monitor spontaneous reversion to negative cultures. Based on the literature, we estimate that mirage de tuberculose occurs in approximately one-third of individuals infected with MTB who exhibit no symptoms. Despite the inherently limited nature of these findings, they suggest that the significance of mirage de tuberculose may be greater than currently perceived. Managing cases of mirage de tuberculose presents formidable challenges from a public health perspective. Striking a balance between prompt treatment initiation to prevent transmission and the risk of unnecessary treatment requires careful consideration. In conclusion, mirage de tuberculose remains a poorly understood clinical entity with very limited literature available. Advancing research and interdisciplinary collaborations are essential to unravel the intricacies of this phenomenon and develop effective strategies to address its public health challenges.

L'apparition d'une culture transitoire positive pour Mycobacterium tuberculosis (MTB), connue sous le nom de mirage de tuberculose, pose des défis importants dans la compréhension de son spectre et de ses implications. Nous rapportons ici un cas de positivité transitoire des cultures, oscillant entre des cultures MTB détectables et non détectables avec des caractéristiques radiologiques minimales et passons en revue la littérature sur ce phénomène. La rareté de la littérature scientifique sur ce sujet provient de l'impossibilité inhérente d'étudier systématiquement le mirage de tuberculose. Des préoccupations éthiques et de santé publique empêchent l'interruption du traitement pour surveiller le retour spontané à des cultures négatives. Sur la base de la littérature, nous estimons que le mirage de tuberculose survient chez environ un tiers des personnes infectées par le MTB qui ne présentent aucun symptôme. Malgré la nature intrinsèquement limitée de ces résultats, ils suggèrent que l'importance du mirage de tuberculose pourrait être plus grande que ce que l'on perçoit actuellement. La prise en charge des mirages de tuberculose présente des défis considérables du point de vue de la santé publique. Il faut trouver un équilibre entre l'instauration rapide du traitement pour prévenir la transmission et le risque d'un traitement inutile. En conclusion, le mirage de tuberculose reste une entité clinique mal comprise et la littérature disponible est très limitée. L'avancement de la recherche et les collaborations interdisciplinaires sont essentiels pour démêler les subtilités de ce phénomène et élaborer des stratégies efficaces pour relever ses défis en matière de santé publique.

Visual cortical responses to the input from the amblyopic eye are suppressed during binocular viewing.

Amblyopia is a visual disorder caused by an anomalous early visual experience. It has been suggested that suppression of the visual input from the weaker eye might be a primary underlying mechanism of the amblyopic syndrome. However, it is still an unresolved question to what extent neural responses to the visual information coming from the amblyopic eye are suppressed during binocular viewing. To address this question we measured event-related potentials (ERP) to foveal face stimuli in amblyopic patients, both in monocular and binocular viewing conditions. The results revealed no difference in the amplitude and latency of early components of the ERP responses between the binocular and fellow eye stimulation. On the other hand, early ERP components were reduced and delayed in the case of monocular stimulation of the amblyopic eye as compared to the fellow eye stimulation or to binocular viewing. The magnitude of the amblyopic effect measured on the ERP amplitudes was comparable to that found on the fMRI responses in the fusiform face area using the same face stimuli and task conditions. Our findings showing that the amblyopic effects present on the early ERP components in the case of monocular stimulation are not manifested in the ERP responses during binocular viewing suggest that input from the amblyopic eye is completely suppressed already at the earliest stages of visual cortical processing when stimuli are viewed by both eyes.

Interferon-γ release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis.

Interferon-γ release assays (IGRAs) are now established for the immunodiagnosis of latent infection with Mycobacterium tuberculosis in many countries. However, the role of IGRAs for the diagnosis of active tuberculosis (TB) remains unclear. Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) and quality assessment of diagnostic accuracy studies (QUADAS) guidelines, we searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001-November 2009 that evaluated the evidence of using QuantiFERON-TB® Gold in-tube (QFT-G-IT) and T-SPOT.TB® directly on blood or extrasanguinous specimens for the diagnosis of active TB. The literature search yielded 844 studies and 27 met the inclusion criteria. In blood and extrasanguinous fluids, the pooled sensitivity for the diagnosis of active TB was 80% (95% CI 75-84%) and 48% (95% CI 39-58%) for QFT-G-IT, and 81% (95% CI 78-84%) and 88% (confirmed and unconfirmed cases) (95% CI 82-92%) for T-SPOT.TB®, respectively. In blood and extrasanguinous fluids, the pooled specificity was 79% (95% CI 75-82%) and 82% (95% CI 70-91%) for QFT-G-IT, and 59% (95% CI 56-62%) and 82% (95% CI 78-86%) for T-SPOT.TB®, respectively. Although the diagnostic sensitivities of both IGRAs were higher than that of tuberculin skin tests, it was still not high enough to use as a rule out test for TB. Positive evidence for the use of IGRAs in compartments other than blood will require more independent and carefully designed prospective studies.

The third-generation P-glycoprotein inhibitor tariquidar may overcome bacterial multidrug resistance by increasing intracellular drug concentration.

OBJECTIVES: The use of efflux pump inhibitors may be a powerful strategy to overcome transporter-mediated bacterial multidrug resistance. In the present study, we set out to investigate the potency of tariquidar, a third-generation P-glycoprotein inhibitor in clinical development, for overcoming bacterial resistance towards ciprofloxacin. METHODS: Staphylococcus aureus 29213 (SA29213) and S. aureus 1199B (SA1199B), which overexpresses the multidrug transporter NorA, as well as Pseudomonas aeruginosa 27853 and Stenotrophomonas maltophilia BAA-85, which expresses SmeDEF, were exposed to ciprofloxacin in the presence and absence of tariquidar or, for comparative reasons, elacridar. Activity of both P-glycoprotein inhibitors was evaluated by determination of MICs and time-kill curves, and by quantification of uptake of ciprofloxacin into bacterial cells. RESULTS: Activity of tariquidar and elacridar was comparable for S. aureus strains, and both dose-dependently increased susceptibility towards ciprofloxacin. Highest effects were observed for SA1199B, where the addition of tariquidar resulted in a 10-fold reduction of the ciprofloxacin MIC, while no effect was observed for P. aeruginosa. For S. maltophilia, elacridar but not tariquidar improved susceptibility. Uptake of [14C]ciprofloxacin and modification of susceptibility showed significant correlations (r=0.89, P<0.0001). Tariquidar had no intrinsic activity against any strain tested. CONCLUSIONS: We conclude that tariquidar has potent inhibitory effect against certain bacterial efflux pumps in vitro. Their high activity at clinically achievable concentrations might yield this class of drugs promising for future applications in infectious diseases.

Cone function in children with a history of preterm birth.

Color vision was examined by psychophysical tests and photopic color full-field electroretinography (ERG) in formerly preterm children, and compared with those of full-term children. In a prospective case-control study, 25 patients with a history of preterm birth 7-14 years of age were divided into three groups: group I, laser-treated retinopathy of prematurity [ROP] (n = 7); group II, spontaneously regressed ROP (n = 8); group III, no ROP (n = 10). Age-matched full-term born children comprised the control group (n = 8). Color vision was assessed by Fansworth D15 and Lanthony desaturated D15 tests. The cone function was tested using photopic full-field ERG. Besides the ISCEV standard stimuli, blue light on amber background was also used (S-cone ERG). The correlation between ERG parameters and prematurity or ROP was determined. We found no significant differences between any patient group and the control group in the results of the psychophysical tests, and implicit times of the ERG responses. The ERG b-wave amplitudes were significantly lower in group I (laser-treated ROP) compared to controls, for 2 of 4 stimulus conditions i.e. the standard (P = 0.028) and S-cone (P = 0.017) single flash ERGs. The general estimating equation model statistics found a significant effect of prematurity on the b-wave amplitudes (P = 0.025, standard, P = 0.014, S-cone ERG). A slightly reduced photopic ERG b-wave amplitude may be associated with prematurity.

[Prognostic factors and visual outcome for open globe injuries with intraocular foreign bodies]. / Prognostische Faktoren und klinische Ergebnisse in der Behandlung von offenen Augenverletzungen mit intraokularen Fremdkörpern.

AIMS: The aim of this study was to evaluate the clinical features as well as the visual results and determine the prognostic factors after the removal of retained intraocular foreign bodies (IOFBs). PATIENTS AND METHODS: At our centre we conducted a non-randomised, non-comparative retrospective analysis of records of 31 patients with intraocular foreign bodies treated using pars plana vitrectomy and other conventional surgical techniques during a 3-year period between January 2006 and December 2008. Using the OTS classification for ocular injuries (United States Eye Injury Registry [USEIR]), we evaluated the visual outcome and various pre-, intra- and postoperative clinical factors. RESULTS: Almost all patients (96.8 %) were male with a mean age of 32.29 years ± 13.38 SD (SD = standard deviation). The most common cause of ocular injury was hammering (58 %), in 27 cases the IOFB was magnetic. Follow-up ranged from 1 to 34 months with a mean of 4.5 months. In 30 eyes, the IOFBs could be removed during the first surgery. The average time between injury and surgery was 15.78 ± 23.45 SD hours for 27 patients (87.1 %). In 3 cases the intraocular foreign body (IOFB) was removed 7, 9, 14 days after the injury. In one case the IOFB was removed in a second surgery 40 days after the injury. In 23 cases we performed pars plana vitrectomy, for 8 patients we performed anterior segment surgery, in 21 cases the lens was also removed. At the time of surgery initial vitreous haemorrhage was present in 17 patients (54.8 %). OTS score for ocular injury was calculated as 2.45 ± 0.78 SD. Initial visual acuity was below 20 / 200 in 61.3 % of the cases. Subsequent to surgical treatment over a mean follow-up of 2.5 months, 25 patients (80.64 %) achieved a visual acuity of 20 / 200 or better (0.69 ± 0.35 SD). Best corrected visual acuity was significantly better for ocular injuries with a higher OTS score (p = 0.000095). Other significant factors for good visual outcome were good initial visual acuity (p = 0.002), the absence of vitreal haemorrhagies (p = 0.024) and small size of the IOFB (p = 0.043). Postoperative complications included retinal detachment (9.67 %), endophthalmitis (3.22 %) and PVR (3.22 %). CONCLUSION: Acceptable visual results could be achieved after the removal of posterior segment IOFBs by vitrectomy. A reliable classification of ocular injuries may provide significant information about the prognosis of injuries with intraocular foreign bodies.

Alterations of pituitary adenylate cyclase-activating polypeptide-like immunoreactivity in the human plasma during pregnancy and after birth.

BACKGROUND: Since its discovery, several distinct effects of pituitary adenylate cyclase activating polypeptide (PACAP) have been established - predominantly in animal studies - in the nervous system, various peripheral organs as well as in the endocrine regulation. It is unknown whether PACAP has any effect on human pregnancy regarding either utero-maternal or perinatal aspects of the gestation. AIM: We investigated alterations of PACAP38-like immunoreactivity (PACAP38-LI) in the human plasma throughout normal pregnancy, during and after delivery, and its level in the umbilical vessels, as well as in the peripheral blood of term healthy newborns. MATERIALS AND METHODS: A 2 ml blood sample was used for each test, PACAP38-LI was determined by radioimmunoassay. RESULTS: In the 2nd and 3rd trimester significant elevation was observed in the PACAP38-LI compared to the earlier gestation and non-pregnant conditions. During delivery its level significantly decreased and returned to the original values 3 days after birth. In the neonates PACAP38-LI level of the peripheral blood was similar to that of healthy adults, but umbilical arteries and veins contained significantly lower concentrations of PACAP38-LI. Besides, the levels were lower in the umbilical vein compared to the artery. CONCLUSIONS: PACAP38-LI levels show sensitive change during normal pregnancy and delivery. Our findings suggest that the fetal organs actively synthesize PACAP. Further investigations are required to elucidate the physiological importance of the alterations observed.

Dirofilaria infections in working dogs in Slovakia.

A monitoring programme aimed at the diagnosis of subcutaneous dirofilariasis and heartworm disease in working (police and military) dogs in Slovakia has been performed during the period of September 2007 to February 2008. In co-operation with the Ministry of the Interior and the Ministry of Defence, in total, 710 dogs (591 police dogs and 119 military dogs) were investigated for the presence of microfilariae in blood. All police and military dogs in active service held on the territory of Slovakia were included. Microfilariae were detected in 118 (20.0%) police dogs and 10 (8.4%) military dogs. The most infected individuals originated from southern parts of Slovakia (Trnava region 53.6% and Nitra region 39.6%); the prevalence was low in northern regions (Zilina 3.1% and Presov 6.6%). In several districts of southern Slovakia, the prevalence of subcutaneous dirofilariasis in working dogs exceeded 40%. In all infected animals, the autochthonous origin of the disease was confirmed; however, due to the frequent movement of working dogs, it was not possible to identify the exact locality of infection. At present, a dog living in Nemsová village in Trencín district (north-western part of the country) is regarded as the northernmost localized autochthonous case of subcutaneous dirofilariasis in Slovakia. In three dogs, co-infection of Dirofilaria repens and Dirofilaria immitis was detected. High prevalence rates in working dogs and the zoonotic characteristic of the disease represent an undoubtedly important veterinary and medical problem that requires the urgent introduction of prophylactic and control measures.

Recruitment of Mycobacterium tuberculosis specific CD4+ T cells to the site of infection for diagnosis of active tuberculosis.

UNLABELLED: Accurate and early diagnosis of active tuberculosis (TB) is problematic as current diagnostic methods show low sensitivity (acid-fast bacilli smears), are time-consuming (culture of biological samples) or show variable results [Mycobacterium tuberculosis (MTB)-specific PCR]. OBJECTIVES: In the course of infection, MTB-specific T cells clonally expand at the site of infection and may thus be used as diagnostic marker for active disease. DESIGN: In this cohort study, the frequency of MTB-specific, interferon (IFN)-gamma expressing CD4(+) T cells obtained from peripheral blood and the site of disease in 25 patients with suspected TB was assessed (n = 11, bronchoalveolar lavage; n = 7, pleural fluid; n = 1, ascites; n = 1, joint fluid; n = 5, cerebrospinal fluid). RESULTS: Amongst 15 patients who showed proven active TB infection, a striking increase of MTB-specific T cells was detected at the site of infection compared with peripheral blood (median increase: 28.5-fold, range: 7.25-531 fold; median of IFN-gamma-producing CD4(+) T cells from blood: 0.02%, range: 0-0.52%; median of IFN-gamma-producing CD4(+) T cells from the site of infection: 1.81%, range: 0.29-6.55%, P < 0.001). MAIN OUTCOME MEASURE: Recruitment of MTB-specific T cells to the site of infection yielded a sensitivity of 100% and specificity of 90%, irrespective of the compartment affected. CONCLUSIONS: The accumulation of MTB-specific T cells at the site of infection may prove as useful diagnostic marker for an accurate and rapid diagnosis of active TB.

Characteristics of interstitial lung disease in SS-A positive/Jo-1 positive inflammatory myopathy patients.

The strongest predictive factor for the development of interstitial lung disease (ILD) in myositis (IIM) patients is the presence of different antisynthetase antibodies. The aim of this study was to compare the clinical characteristics, radiological findings and therapeutic response between the anti-SS-A positive and negative antisynthetase syndrome (ASS) patients. A prospective study of 315 IIM patients was conducted including 27 anti-Jo-1 positive ASS patients. Mean disease duration was 46.6 (range 4-198) months. All patients fulfilled the classification criteria for IIM. All patients underwent chest radiography, pulmonary function tests and HRCT at he time of diagnosis and 6 months after the immunosuppressive therapy. Routine laboratory tests, RF, ANA, anti-ENA, anti-SS-A, anti-histidyl-transfer RNA antibody (Jo-1) measurements were performed in all patients. ILD was found to be present in 70.4% of ASS patients. The anti-SS-A negative ASS group had a more frequent association with alveolitis and responded well to immunosuppressive therapy (p < 0.05). HRCT scan showed more fibrosis in the SS-A positive group. 15.8% of patients died due to pulmonary or cardiac complications. In conclusion, coexistence of anti-SS-A and anti-Jo-1 antibody may be a good predictor for a more coarse and severe ILD in IIM patients who require a more aggressive approach in therapy.

Changes and effect of PACAP-38 on intestinal ischemia-reperfusion and autotransplantation.

Tissue injury caused by cold preservation and reperfusion during small bowel transplantation remains an unsolved problem. Increasing evidence suggests that pituitary adenylate cyclase-activating polypeptide (PACAP) has protective effects in several ischemia-reperfusion (I/R) models. This study investigated the effect of PACAP-38 on oxidative stress in autotransplanted intestine. We established sham-operated, I/R, and autotransplanted groups in Wistar rats (n = 55). We applied ischemia for 1 (GI), 2 (GII), or 3 hours (GIII). In autotransplanted groups, we performed total orthotopic intestinal autotransplantation. Grafts were preserved in University of Wisconsin (UW) solution for 1 (GIV), 2 (GV), 3 (GVI), or 6 (GVII) hours and in PACAP-38-containing UW for 1 (GVIII), 2 (GIX), 3 (GX), or 6 (GXI) hours. Reperfusion lasted 3 hours in each group. Endogenous PACAP-38 values were measured by radioimmunoassay. Oxidative stress parameters malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) were measured in tissue homogenates. Concentration of endogenous PACAP-38 significantly decreased in GI to GIII compared with the sham-operated animals following I/R periods (P < .05). Cold preservation in UW and reperfusion of the intestine increased the level of tissue MDA in GIV to GVII, which correlated with the duration of cold storage. The content of GSH decreased in GIV to GVII to levels that were significantly different between GIV and GVIII and between GVII and GXI. SOD activity decreased dramatically in GIV to GVII with significantly higher activity in GIX to GXI. Our findings confirmed that I/R decreased endogenous PACAP-38 concentration. Administration of PACAP-38 to UW solution mitigated the oxidative injury during intestinal autotransplantation.

[Imaging of gastrointestinal stromal tumors]. / Imagerie des tumeurs stromales digestives.

Gastrointestinal stromal tumors (GIST) arising from interstitial cells of Cajal, represent the first type of solid tumor, which is very sensitive to a specific molecularly targeted tyrosine kinase receptor blocker (i. e., imatinib). On CT, which is considered as the reference technique, GISTs typically present as large, well-delineated, heterogeneous and sometimes exophytic masses. In contrast with the absence of lymph node involvement, hepatic metastasis as well as mesenteric involvement can be observed. MR-enteroclysis is indicated to investigate the local extent of the disease in specific cases whereas MR imaging is used to detect hepatic metastasis. Because of a specific treatment, contrast-enhanced imaging is needed for the follow-up of treated tumors. Evaluation of tumor response to treatment is best assessed with CT which still remains the reference imaging technique whereas FDG-PET imaging is used in specific cases.

The antiapoptotic effect of IL-6 autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1.

Levels of the proinflammatory cytokine interleukin-6 (IL-6) are increased in therapy-resistant prostate cancer. IL-6 has been considered a positive growth factor in late-stage prostate cancer cells and a potential target for therapeutic interference. Effects of inhibition of IL-6 on cell survival were studied in LNCaP-IL6+ cells, a model system for advanced prostate cancer, which produce IL-6. We show that the autocrine IL-6 loop is responsible for resistance to apoptosis and increased cellular levels of myeloid cell leukemia-1 (Mcl-1) protein, an antiapoptotic member of the Bcl-2 family. Treatment of cells with a chimeric anti-IL-6 antibody (CNTO 328) led to the induction of apoptosis and downregulation of Mcl-1 protein levels. Specific knockdown of Mcl-1 gene expression by small interfering RNA also yielded an increase in apoptosis of LNCaP-IL-6+ cells. Vice versa, inactivation of IL-6 autocrine loop had no influence on apoptosis levels in the absence of Mcl-1, thus suggesting this molecule as a mediator of the survival action of IL-6. Mcl-1 protein regulation by the endogenous cytokine directly involved the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway. Our data support the concept of anti-IL-6 targeted therapy in therapy-resistant prostate cancer.

The presence and distribution of pituitary adenylate cyclase activating polypeptide and its receptor in the snail Helix pomatia.

The aim of this study was to show the presence, distribution and function of the pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors in the CNS and peripheral nervous system of the mollusk, Helix pomatia. PACAP-like and pituitary adenylate cyclase activating polypeptide receptor (PAC1-R)-like immunoreactivity was abundant both in the CNS and the peripheral nervous system of the snail. In addition several non-neuronal cells also revealed PACAP-like immunoreactivity. In inactive animals labeled cell bodies were mainly found and in the neuropile of active animals dense immunostained fiber system was additionally detected suggesting that expression of PACAP-like peptide was affected by the behavioral state of the animal. RIA measurements revealed the existence of both forms of PACAP in the CNS where the 27 amino acid form was found to be dominant. The concentration of PACAP27 was significantly higher in samples from active animals supporting the data obtained by immunohistochemistry. In Western blot experiments PACAP27 and PACAP38 antibodies specifically labeled protein band at 4.5 kDa both in rat and snail brain homogenates, and additionally an approximately 14 kDa band in snail. The 4.5 kDa protein corresponds to PACAP38 and the 14 kDa protein corresponds to the preproPACAP or to a PACAP-like peptide having larger molecular weight than mammalian PACAP38. In matrix-assisted laser desorption ionization time of flight (MALDI TOF) measurements fragments of PACAP38 were identified in brain samples suggesting the presence of a large molecular weight peptide in the snail. Applying antibodies developed against the PACAP receptor PAC1-R, immunopositive stained neurons and a dense network of fibers were identified in each of the ganglia. In electrophysiological experiments, extracellular application of PACAP27 and PACAP38 transiently depolarized or increased postsynaptic activity of neurons expressing PAC1-R. In several neurons PACAP elicited a long lasting hyperpolarization which was eliminated after 1.5 h continuous washing. Taken together, these results indicate that PACAP may have significant role in a wide range of basic physiological functions in snail.

Agonistic behavior of PACAP6-38 on sensory nerve terminals and cytotrophoblast cells.

The effects of pituitary adenylate cyclase activating polypeptide (PACAP) are mediated through G-protein-coupled receptors, the specific PAC1 receptor and VPAC1 and VPAC2 receptors which bind vasoactive intestinal peptide with similar affinity. Based on binding affinity studies, PACAP6-38 was discovered as a potent antagonist of PAC1 and it has been used by hundreds of studies as a PACAP antagonist. Recently, we have found that in certain cells/tissues, PACAP6-38 does not antagonize PACAP-induced effects, but surprisingly, it exerts similar actions to PACAP1-38, behaving as an agonist. In the present study, we report on the agonistic behavior of PACAP6-38 on neuropeptide release from sensory nerves of the isolated rat trachea and on the MAPK signaling pathways in cytotrophoblast cells. In isolated rat tracheae, PACAP6-38, similarly to PACAP1-38, induced significant inhibitory effects on the release of three simultaneously measured sensory neuropeptides, substance P, calcitonin gene-related peptide, and somatostatin evoked by both chemical excitation and electrical field stimulation of capsaicin-sensitive afferents. Effects of PACAP6-38 were the same as those of PACAP1-38 on MAPK signaling in human cytotrophoblast cells. Western blot analysis showed that both peptide forms stimulated ERK1/2 and JNK phosphorylation, while they both inhibited p38 MAPK phosphorylation. The most pronounced effects were observed when both peptides were present. In summary, our results show that PACAP6-38, which is a PACAP receptor antagonist in most cells/tissues, can behave as an agonist in other systems. The increasing interest in the effects of PACAP requires further studies on the pharmacological properties of the peptide and its analogues.

Confocal microscopic evidence of increased Langerhans cell activity after corneal metal foreign body removal.

PURPOSE: The purpose of the study was to examine the corneal inflammatory reaction and Langerhans cells with confocal microscopy after metal foreign body removal. METHODS: Corneal metal foreign body was removed from 9 eyes of 9 consecutive patients 12.1+/-13.6 (4 to 72) hours after superficial angle grinder injury. Both eyes were examined with the Heidelberg Retina Tomograph II (HRT II) Rostock Cornea Module. Morphology and density of epithelium, nerves, metal deposits, keratocytes, endothelium, and Langerhans cells were compared to the uninjured fellow eyes (controls). RESULTS: Irregularity and partially missing superficial epithelium was found in all cases. Around the area of injury prolonged basal and wing epithelial cells were found in all eyes. The basal epithelium density is lower than in the control eye (p=0.043). Density of Langerhans cells (68.1+/-24.2/mm2) was increased in the epithelium, compared to controls (35.2+/-21.8/mm2, p=0.012). Keratocyte and endothelium densities were not different from that of controls. Some keratocytes showed signs of activation and the inhomogeneous background reflectivity revealed extracellular matrix alterations. Inflammatory reaction was observed up to260 micronm depth. The metal foreign body particles had high reflectivity and irregular edge. CONCLUSIONS: In vivo confocal microscopy provided additional information to biomicroscopic signs such as epithelial damage and inflammation. It showed the effects of metal foreign bodies in the cornea: nerve damage and Langerhans cell density increase. Langerhans cells seem to play an important role in the inflammatory response after corneal foreign body injuries.

First Report of Bacterial Fruit Blotch of Watermelon Caused by Acidovorax avenae subsp. citrulli in Hungary.

Typical bacterial fruit blotch (BFB) symptoms were observed on cvs. Crisby, Suzy, Top Gun, and Lady watermelon (Citrullus lanatus (Thunb.) Matsum. & Nakai.) fruits in southeastern Hungary (Medgyesegyháza) in July 2007 when the mean maximum daytime temperature was greater than 32°C. Approximately 20 to 30 ha of watermelons were observed to be affected by the disease. Source of the infection was not determined, however, grafted watermelon transplants that were grown in this area had been imported from Turkey where the pathogen is present (2). Disease symptoms started with irregularly shaped, water-soaked lesions on the surface of the fruits. The lesions enlarged and the epidermis became brown and cracked. BFB symptoms were not readily visible on mature foliage. Colonies of the BFB pathogen were creamy white on nutrient agar (Difco, Detroit, MI). Strains were gram negative, oxidase positive, and produced acid from glucose aerobically. A cell suspension (50 µl of ~1 × 107 CFU/ml) from a 24-h nutrient plate culture was infiltrated with a hypodermic syringe into the intercellular spaces of fully developed intact tobacco (Nicotiana tabacum L. cv. White Burley) leaves to determine the hypersensitive reaction (HR) (1). A typical HR developed 20 h after leaf infiltration. Bacterial pathogenicity was tested on surface-sterilized, mature fruits of different plant species by injecting cell suspensions into the fruit tissues as previously described (each fruit was injected in five places; the negative control (sterile water) as well). Fruits were incubated for 7 days at 25°C and then observed for symptom development. Necrosis was observed at each point of inoculation with the pathogen for watermelon and green pepper (Capsicum annuum L.). Necrosis was also observed for cucumber (Cucumis sativus L.), zucchini (Cucurbita pepo L. convar. giromontiina Greb.), squash (C. pepo L.), and patisson (C. pepo L. convar. patissoniana Greb.). Necrosis was not observed when the pathogen was inoculated onto fruit of melon (Cucumis melo L.), tomato (Lycopersicon esculentum Mill.), and eggplant (Solanum melongena L.). Additionally, symptoms were not observed at the points inoculated with sterile water (negative control) for any of the fruits tested. To identify the pathogen, PCR was used with Acidovorax avenae subsp. citrulli-specific primers WFB1/2 (4). The 16s rDNA region amplified with a general bacterial primer pair (63f forward and 1389r reverse) (3) was cloned into a pBSK+ vector (Stratagene, La Jolla, CA) and sequenced by M13 forward and reverse primers (GenBank Accession No. AM850114). On the basis of the symptoms, biochemical tests (API 20NE; Biomérieux, Marcy l'Etoile, France), fatty acid methyl ester analysis (74.5 to 83.6% similarity), and 16SrDNA sequence homology (100% sequence similarity with AAC00-1), the pathogen was identified as A. avenae subsp. citrulli. To our knowledge, this is the first report of BFB of watermelon in Hungary. References: (1) Z. Klement. Nature 199:299, 1963. (2) M. Mirik et al. Plant Dis. 6:829, 2006. (3) A. M. Osborn et al. Environ. Microbiol. 2:39, 2000. (4) R. R. Walcott and R. D. Gitaitis. Plant Dis. 84:470, 2000.

Modulation of central endocannabinoid system results in gastric mucosal protection in the rat.

Previous findings showed that inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), degrading enzymes of anandamide (2-AEA) and 2-arachidonoylglycerol (2-AG), reduced the nonsteroidal anti-inflammatory drug-induced gastric lesions. The present study aimed to investigate: i./whether central or peripheral mechanism play a major role in the gastroprotective effect of inhibitors of FAAH, MAGL and AEA uptake, ii./which peripheral mechanism(s) may play a role in mucosal protective effect of FAAH, MAGL and uptake inhibitors. METHODS: Gastric mucosal damage was induced by acidified ethanol. Gastric motility was measured in anesthetized rats. Catalepsy and the body temperature were also evaluated. Mucosal calcitonin gene-related peptide (CGRP), somatostatin concentrations and superoxide dismutase (SOD) activity were measured. The compounds were injected intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.). RESULTS: 1. URB 597, JZL184 (inhibitors of FAAH and MAGL) and AM 404 (inhibitor of AEA uptake) decreased the mucosal lesions significantly given either i.c.v. or i.p. 2. URB 937, the peripherally restricted FAAH inhibitor failed to exert significant action injected i.p. 3. Ethanol-induced decreased levels of mucosal CGRP and somatostatin were reversed by URB 597, JZL 184 and AM 404, the decreased SOD activity was elevated significantly by URB 597 and JZL 184. 4. Neither compounds given i.c.v. influenced gastric motility, elicited catalepsy, or hypothermia. CONCLUSION: Elevation of central endocannabinoid levels by blocking their degradation or uptake via stimulation of mucosal defensive mechanisms resulted in gastroprotective action against ethanol-induced mucosal injury. These findings might suggest that central endocannabinoid system may play a role in gastric mucosal defense and maintenance of mucosal integrity.