Matched case-control comparison of surgical success after XEN45 Gel Stent and PRESERFLO MicroShunt implantation in a Caucasian population.

BACKGROUND: The aim of this study was to compare the outcome of implantation of a XEN45 Gel Stent with the outcome of implantation of a Preserflo MicroShunt in a matched-pair analysis in eyes being naïve to filtering surgery. METHODS: In this comparative, retrospective study, 50 eyes that had undergone XEN45 Gel Stent implantation were compared with 50 eyes after Preserflo implantation. Follow-up was at least 6 months, and surgical success was measured by criteria A (IOP < 21 mmHg, IOP reduction >20%, no repeat surgery); criteria B (IOP < 18 mmHg, IOP reduction >20%, no repeat surgery); and criteria C (IOP ≤15 mmHg, IOP reduction ≥40%, no repeat surgery). RESULTS: After a follow-up period of 12 months, mean IOP had decreased from preoperative 25.2 ± 4.8 mmHg in the XEN group to 14.5 ± 4.0 (n = 35) and from 25.3 ± 6.8 mmHg to 11.9 ± 2.9 (n = 41) in the Preserflo group, respectively. The IOP at the last follow-up of the two groups differed significantly (p < 0.01). The probability of surgical success did not differ concerning Criteria A and B, but surgical success was significantly higher in the Preserflo group for Criteria C (60%, p < 0.01). CONCLUSION: Both the Preserflo and XEN45 Gel Stent provide an effective and safe treatment option for advanced glaucoma and have a high potential to reduce intraocular pressure. Absolute IOP levels of <16 mmHg after 12 months were significantly more frequent in the Preserflo group.

Predictability of success for combined iStent inject trabecular bypass implantation with phacoemulsification in the subsequent eye.

BACKGROUND: To investigate in combined iStent inject implantation with phacoemulsification carried out bilaterally, whether intraocular pressure (IOP)-lowering effectiveness in the first eye has a predictive potential for the outcome of the second eye in primary open-angle glaucoma (POAG). METHODS: This retrospective study included 72 eyes from 36 participants, who underwent trabecular bypass implantation in combination with cataract surgery at two study centres (Düsseldorf, Cologne). Surgery was classified as either 'success' or 'failure' based on three scores: IOP at follow-up <21 mmHg (Score A) or IOP < 18 mmHg (Score B), with an IOP reduction >20% respectively, without re-surgery and IOP ≤ 15 mmHg with an IOP reduction ≥40%, without re-surgery (Score C). RESULTS: The IOP lowering outcomes of first and second eyes did not differ significantly. There was a significantly higher chance of success in the second eye after effective surgery in the first eye compared with cases after a preceding failure. Within our cohort, a 76% probability of success for the subsequent eye was determined following prior success for Score A. This probability was reduced to 13% if surgery in the first eye failed. The respective probabilities were 75% and 13% for Score B and 40% and 7% for Score C. CONCLUSIONS: In bilateral trabecular bypass implantation combined with cataract surgery, there is a high predictive potential for subsequent eyes based on the extent of IOP-lowering in the initial eye, which should be considered by the surgeon for second eye surgeries.

TREATMENT OF PERSISTENT MACULAR HOLES WITH HEAVY SILICONE OIL.

BACKGROUND/PURPOSE: To determine anatomical success and best-corrected visual acuity after secondary surgery with heavy silicone oil tamponade in patients with persistent full-thickness macular holes. METHODS: In this retrospective study, 63 eyes with persistent full-thickness macular holes after primary pars plana vitrectomy and internal limiting membrane peeling underwent secondary surgery with heavy silicone oil tamponade. Macular spectral domain optical coherence tomography and best-corrected visual acuity measurements were performed during the follow-up. RESULTS: Fifty of 63 eyes (79.4%) achieved anatomical success. In eyes achieving anatomical success, best-corrected visual acuity before primary vitreoretinal surgery was significantly better (0.77 [∼20/125 Snellen] ± 0.24 [1.3-0.3] logarithm of the minimum angle of resolution) compared with eyes not achieving anatomical success (0.88 [∼20/160 Snellen] ± 0.17 [1.1-0.6] logarithm of the minimum angle of resolution, P = 0.044). Minimum linear diameter of full-thickness macular holes was significantly smaller in eyes achieving anatomical success, both before primary (403.4 ± 128.7 [199.0-707.0] µ m vs. 568.1 ± 209.1 [307.0-953.0] µ m, P = 0.009) and secondary surgery (464.1 ± 215.0 [178.0-1,521.0] µ m vs. 663.3 ± 228.5 [451.0-1,301.0] µ m, P = 0.010). Patients remaining phakic during all three surgeries did not benefit from best-corrected visual acuity improvement, although anatomical success was achieved. CONCLUSION: Heavy silicone oil tamponade in secondary surgery for persistent full-thickness macular holes is a safe and efficient surgical method. Best-corrected visual acuity and minimum linear diameter before surgery may be indicators for anatomical success.

Combined ab-interno trabeculectomy and cataract surgery induces comparable intraocular pressure reduction in supine and sitting positions.

AIM: To analyze the therapeutic effect of combined ab-interno trabeculectomy and cataract surgery on intraocular pressure (IOP) levels in supine and sitting postures during a 24-hour IOP profile. METHODS: Twenty-six eyes of twenty-six patients receiving ab-interno trabeculectomy using electroablation of the trabecular meshwork combined with cataract surgery or stand-alone were included in this retrospective analysis. IOP change during 24-hour IOP profiles within two years postoperatively were analyzed for eyes receiving surgery ("study eyes") and compared to fellow eyes, which had not received surgery. Clinical data including mean sitting IOP (siIOP), mean supine IOP (suIOP) and the number of topical antiglaucomatous medications (TAM) were extracted from patients' files. RESULTS: Preoperatively, siIOP was 17.6±5.3 mm Hg in study and 17.1±4.7 mm Hg in fellow eyes (P=0.347). Patients were treated with an average of 2.8±1.0 TAM. Best corrected visual acuity (BCVA) was significantly worse in study eyes (P<0.001), visual field function was marginally not significantly different (P=0.057). After surgery 9.6±6.8mo, study eyes had a mean siIOP of 14.5±3.6 mm Hg (IOP reduction: -3.2 mm Hg, P=0.009), a mean suIOP of 18.0±3.5 mm Hg, and an average of 1.3±1.34 TAM (P<0.001), while in fellow eyes, mean siIOP was 16.2±3.4 mm Hg and mean suIOP was 20.5±5.1 mm Hg. Postoperatively, the relative IOP increase between sitting and supine postures was approximately 30% in both study and fellow eyes (P=0.99). CONCLUSION: IOP after ab-interno trabeculectomy shows a comparable relative reduction in both supine and sitting position. Classical trabeculectomy is known to lower suIOP overproportionally.

A Case of Endocarditis Following Endophthalmitis After XEN45 Gel Stent Implantation.

INTRODUCTION: We report a case of endophthalmitis and endocarditis that developed after stent perforation following a XEN45 Gel Stent implantation 10 months ago. CASE REPORT: A 79-year-old man was referred to our hospital because of endophthalmitis of the right eye. The patient had undergone XEN45 Gel Stent implantation in the same eye 10 months ago. On examination, the conjunctiva was perforated by the stent, and it was no longer covered by the conjunctiva. A 27-G pars plana vitrectomy with intravitreal antibiotic injection was performed. Moreover, the patient received intravenous antibiotic treatment and local anti-inflammatory and anti-infectious therapy. Streptococcus gordonii was identified as a bacterial cause of the endophthalmitis. Therefore, transesophageal echocardiography was performed, which revealed aortic valve endocarditis. DISCUSSION: Although not proven, it is possible that the exposed XEN45 Gel Stent served as an entry point for S. gordonii, which caused the exogenous endophthalmitis and subsequent endocarditis. S. gordonii belongs to the viridans group streptococci, which is the etiological agent for endocarditis which is a severe and potentially life-threatening infection. Ophthalmologists should therefore consider the risk of systemic infections as endocarditis after endophthalmitis, particularly caused by the viridans group streptococci, which are known etiological agents of endocarditis.

Intraocular lens power calculation for plus and minus lenses in high myopia using partial coherence interferometry.

PURPOSE: We assessed the accuracy of lens power calculation in highly myopic patients implanting plus and minus intraocular lenses (IOL). METHODS: We included 58 consecutive, myopic eyes with an axial length (AL) > 26.0 mm, undergoing phacoemulsification and IOL implantation following biometry using the IOLMaster 500. For lens power calculation, the Haigis formula was used in all cases. For comparison, refraction was back-calculated using the Barrett Universal II (Barrett), Holladay I, Hill-RBF (RBF) and SRK/T formulae. RESULTS: The mean axial length was 30.17 ± 2.67 mm. Barrett (80%), Haigis (87%) and RBF (82%) showed comparable numbers of IOLs within 1 diopter (D) of target refraction. Visual acuity (BSCVA) improved (p < 0.001) from 0.60 ± 0.35 to 0.29 ± 0.29 logMAR (> 28-days postsurgery). The median absolute error (MedAE) of Barrett 0.49 D, Haigis 0.38, RBF 0.44 and SRK/T 0.44 did not differ. The MedAE of Haigis was significantly smaller than Holladay (0.75 D; p = 0.01). All median postoperative refractive errors (MedRE) differed significantly with the exception of Haigis to SRK/T (p = 0.6): Barrett - 0.33 D, Haigis 0.25, Holladay 0.63, RBF 0.04 and SRK/T 0.13. Barrett, Haigis, Holladay and RBF showed a tendency for higher MedAEs in their minus compared to plus IOLs, which only reached significance for SRK/T (p = 0.001). Barrett (p < 0.001) and RBF (p = 0.04) showed myopic, SRK/T (p = 002) a hyperopic shift in their minus IOLs. CONCLUSIONS: In highly myopic patients, the accuracies of Barrett, Haigis and RBF were comparable with a tendency for higher MedAEs in minus IOLs. Barrett and RBF showed myopic, SRK/T a hyperopic shift in their minus IOLs.

Predictability of ab-interno trabeculectomy success in the subsequent eye: A contralateral eye comparison study.

BACKGROUND: To determine whether the outcome of the first eye may serve as a predictor for intraocular pressure (IOP)-lowering effectiveness in the second eye following bilateral ab interno trabeculectomy. METHODS: This retrospective single-centre study included 168 eyes from 84 participants, who underwent combined Trabectome surgery with phacoemulsification cataract surgery in a hospital setting. The clinical endpoint was defined as either 'success' or 'failure' based on four separate scores at the longest follow-up time point: IOP at follow-up <21 mm Hg (Score A) or IOP < 18 mm Hg (Score B), without re-surgery and IOP reduction >20%; IOP ≤15 mm Hg without re-surgery and IOP reduction ≥40% (Score C); and the sole absence of re-surgery according to the discretion of the surgeon (Score D). RESULTS: No significant difference was observed between the outcomes of first and second eyes. The frequency of success in the second eye after effective surgery in the first eye significantly exceeded that after prior failure. Within our analysis, the probability calculations determined a 75% chance of success following prior success for Score A. If surgery in the first eye failed, the chance of success in the subsequent eye was 37%. The corresponding probabilities were 79% and 32% for Score B, 56% and 9% for Score C, and 99% and 50% for Score D. CONCLUSION: The results of our study offer a useful tool to assess the success of subsequent eye surgeries based on the outcome in the initial eye, owing to the high predictive potential.

Primary Versus Posttrabeculectomy XEN45 Gel Stent Implantation: Comparison of Success Rates and Intraocular Pressure-lowering Potential in Pseudophakic Eyes.

PRECIS: The XEN45 Gel Stent can be implanted after failed trabeculectomy without disadvantages compared with primary implantation. PURPOSE: We aimed to compare the outcomes of XEN45 Gel Stent implantation in pseudophakic eyes after failed trabeculectomy and in pseudophakic eyes without other previous surgeries. PATIENTS AND METHODS: In this retrospective study, we included 30 pseudophakic eyes of 30 patients who underwent XEN45 Gel Stent implantation after failed trabeculectomy (trabeculectomy group) and 60 eyes of 60 patients with primary XEN45 Gel Stent implantation (control group). The groups were matched for preoperative intraocular pressure (IOP), preoperative medication score, cup-to-disc ratio, follow-up time, visual acuity, and age at a ratio of 1:2. Eyes with concomitant eye diseases, those who had undergone previous surgery, and those with a follow-up duration <6 months were excluded. We compared the success rates on the basis of different criteria: Criteria A (IOP<21 mm Hg, IOP reduction>20%, no repeat surgery); Criteria B (IOP<18 mm Hg, IOP reduction>20%, no repeat surgery); and Criteria C (IOP≤15 mm Hg, IOP reduction≥40%, no repeat surgery). RESULTS: After an average follow-up period of 20 months, the mean IOP was reduced from 24.4±5.7 to 14.0±4.1 mm Hg in all the study subjects (90 patients). There were no significant differences between the 2 groups in postoperative IOP, postoperative medication score, revision rate, and repeat surgery rate or success rate. CONCLUSIONS: XEN45 Gel Stent implantation is a viable option after failed trabeculectomy. According to our results, it has no disadvantage compared with primary XEN45 Gel Stent implantation.

Correction to: Influence of oral anticoagulation on success rates and risk of bleeding events after iStent inject implantation combined with phacoemulsification.

The published online version contains mistake as the author's first name and last name have been interchanged as "Hild Matthias" instead of "Matthias Hild".

Influence of oral anticoagulation on success rates and risk of bleeding events after iStent inject implantation combined with phacoemulsification.

PURPOSE: We conducted a retrospective study to evaluate the intraocular pressure (IOP) lowering effect, the success rates, and the risk of bleeding events of patients receiving an iStent inject combined with phacoemulsification under anticoagulation therapy compared with a matched control group. METHODS: In this retrospective study, sixty-four eyes underwent an iStent inject implantation combined with phacoemulsification at two centers. Thirty-two eyes received surgery while under anticoagulation therapy, and another thirty-two eyes served as a control group matched for visual acuity, IOP, and medication score. Success was defined as criteria A and B (IOP < 18/21 mmHg, > 20% IOP reduction, no resurgery) and criteria C (IOP ≤ 15 mmHg, IOP reduction ≥ 40%, no resurgery). The clinical goal of the study was to determine the difference between the study and control groups with respect to IOP, medication score, and the frequency of intraoperative and postoperative bleeding events. RESULTS: After a mean follow-up time of 1 year, the IOP lowered 28% from 20.1 ± 4.8 to 14.5 ± 3.7 mmHg in the group of 64 eyes. The medication score lowered 38% from 2.1 ± 1.1 to 1.3 ± 1.2. The two groups with and without anticoagulant agents did not significantly differ in postoperative IOP, medication score, success rates, or number of bleeding events. CONCLUSION: We conclude that in cataract surgery combined with the iStent inject a discontinuation of anticoagulant agents might not be necessary. It might be a good option in glaucoma surgery when anticoagulation treatment should not be interrupted and the target pressure is not very low.

Intraocular Degradation of XEN45 Gel Stent 3 Years After its Implantation.

INTRODUCTION: We report a case of XEN45 Gel Stent removal 3 years after its implantation. The stent had degraded with a closed lumen, so a new stent was implanted. CASE REPORT: A 63-year-old woman was scheduled for XEN45 Gel Stent implantation. Three years after the primary surgery and 2 years after a surgical revision, second revision surgery was required. The conjunctiva was opened, and the implanted XEN Gel Stent was stripped of the adhesive scar tissues. No aqueous humor flow was seen through the stent, and therefore, the stent was removed. The intrascleral and intracameral parts had degraded. The surface of the stent was irregular and cobbled. A part of the lumen in the middle of the stent had closed. DISCUSSION: We detected changes in the stent after its removal during the surgical revision with conjunctival opening, which is our standard approach for failed XEN Gel Stents. Most surgeons advise needling of the stent in cases of failure. However, in cases of needling, changes in the stent might not have been detected. Thus, the number of patients with similar changes as this report might be higher than the publications suggest. No unique characteristics distinguished this patient from those who had a functional XEN Gel Stent. The stent, in this case, might have been of inferior quality as an exception, or all stents might degrade over time. Therefore, gonioscopy should be performed carefully to detect any changes in the stent. In cases of suspected stent degradation, we recommend a revision surgery with conjunctival opening and removal of the stent in cases of degradation.

The XEN45 Gel Stent as a minimally invasive procedure in glaucoma surgery: success rates, risk profile, and rates of re-surgery after 261 surgeries.

PURPOSE: The XEN45 Gel Stent is a flexible hydrophilic tube placed under the conjunctiva via the anterior chamber. This study investigates the IOP (intraocular pressure)-lowering potential, the risk profile, and the success rate of the XEN45 Gel Stent. METHODS: Two hundred and sixty-one eyes underwent surgery. The mean follow-up time was 8.5 months. The aim of the treatment was to achieve adequate IOP reduction without medication. Therefore, all patients who did not show sufficiently reduced IOP underwent a surgical revision with opening of the conjunctiva. To determinate the success rate, we carried out two kinds of analysis: 1) the primary success rate: eyes with appropiate IOP control without medication or surgical revision, and 2) overall success rate: one surgical revision was allowed. RESULTS: Intraocular pressure was lowered from 24.3 mmHg (SD 6.6) to 16.8 mmHg (SD 7.6), and the medication score was lowered from 2.6 (SD 1.1) to 0.2 (SD 0.7). Revisional surgery was performed in 80 eyes (34%). After a first revision, intraocular pressure was lowered to 14.0 mmHg (SD 5.1), and the medication score was lowered to 0.2 (SD 0.6). The primary success rate was 66% and the overall success rate 90%. The primary success rate was higher in pseudophakic eyes (73%) than in phakic eyes (53%) or combined surgery (55%). CONCLUSIONS: We conclude from our data that the XEN45 Gel Stent has an IOP-lowering potential and few side-effects. Pseudophakic eyes seem to have a better primary prognosis compared to combined surgery or surgery in phakic eyes.

Brain-borne IL-1 adjusts glucoregulation and provides fuel support to astrocytes and neurons in an autocrine/paracrine manner.

It is still controversial which mediators regulate energy provision to activated neural cells, as insulin does in peripheral tissues. Interleukin-1ß (IL-1ß) may mediate this effect as it can affect glucoregulation, it is overexpressed in the 'healthy' brain during increased neuronal activity, and it supports high-energy demanding processes such as long-term potentiation, memory and learning. Furthermore, the absence of sustained neuroendocrine and behavioral counterregulation suggests that brain glucose-sensing neurons do not perceive IL-1ß-induced hypoglycemia. Here, we show that IL-1ß adjusts glucoregulation by inducing its own production in the brain, and that IL-1ß-induced hypoglycemia is myeloid differentiation primary response 88 protein (MyD88)-dependent and only partially counteracted by Kir6.2-mediated sensing signaling. Furthermore, we found that, opposite to insulin, IL-1ß stimulates brain metabolism. This effect is absent in MyD88-deficient mice, which have neurobehavioral alterations associated to disorders in glucose homeostasis, as during several psychiatric diseases. IL-1ß effects on brain metabolism are most likely maintained by IL-1ß auto-induction and may reflect a compensatory increase in fuel supply to neural cells. We explore this possibility by directly blocking IL-1 receptors in neural cells. The results showed that, in an activity-dependent and paracrine/autocrine manner, endogenous IL-1 produced by neurons and astrocytes facilitates glucose uptake by these cells. This effect is exacerbated following glutamatergic stimulation and can be passively transferred between cell types. We conclude that the capacity of IL-1ß to provide fuel to neural cells underlies its physiological effects on glucoregulation, synaptic plasticity, learning and memory. However, deregulation of IL-1ß production could contribute to the alterations in brain glucose metabolism that are detected in several neurologic and psychiatric diseases.

A new surgical triple procedure in pseudoexfoliation glaucoma using cataract surgery, Trabectome, and trabecular aspiration.

BACKGROUND: To evaluate the potential of lowering intraocular pressure in pseudoexfoliation glaucoma with combined phacoemulsification, Trabectome, and trabecular aspiration (triple procedure) compared to phacoemulsification and trabecular aspiration alone. METHODS: Using a case-matched retrospective study design, 30 patients were included into each group. The main outcome measures were the reduction of intraocular pressure and medication score at the end of follow-up. Clinical data were collected from the patients' medical records. RESULTS: Mean follow-up was 15 months in both groups. Intraocular pressure decreased from 25.3 ± 6.3 mmHg to 14.4 ± 3.7 mmHg (p < 0.0001) in the triple procedure group and from 25.3 ± 4.2 mmHg to 18.1 ± 4.2 mmHg (p < 0.0001) in the control group. The medication score was lowered from 3.4 ± 1.7 to 2.1 ± 1.2 (p = 0.0017) in the triple procedure group and from 3.8 ± 1.8 to 2.3 ± 1.5 (p < 0.008) in the control group. The reduction of intraocular pressure was higher (p < 0.004) in the triple procedure group (38.4 ± 17.3 %) compared to the control group (26.8 ± 19.6 %) The reduction of the medication score did not differ significantly. CONCLUSIONS: The triple procedure is more effective in lowering intraocular pressure compared to phacoemulsification and trabecular aspiration alone in pseudoexfoliation glaucoma.

The effect of membrane differential filtration on the colloid osmotic pressure in patients with age-related macular degeneration: significance to visual function?

To investigate the effect of membrane differential filtration (MDF) on plasma colloid osmotic pressure (COP) and visual functions in age-related geographic macular degeneration (AMD). Ten consecutive patients with non-exudative AMD underwent one MDF cycle. Primary endpoint was COP. Secondary endpoints were visual acuity and the mean defect of visual field. The COP was markedly reduced after one MDF cycle by 23.9% (P = 0.001). Compared with the baseline examination, visual acuity and the mean defect of visual field improved significantly after MDF. A significant positive correlation was found between the improvement in visual field and the decrease in COP (Pearson's coefficient = 0.65; P = 0.04). Membrane differential filtration lowers plasma colloid osmotic pressure in patients with non-exudative AMD. Based on the observation that visual field and COP are correlated, one may hope for a means to improve decreased central retinal function in eyes with geographic AMD by modulation of COP plasma level.

A case of angle-closure glaucoma, cataract, nanophthalmos and spherophakia in oculo-dento-digital syndrome.

BACKGROUND: We report a new case of oculo-dento-digital syndrome. METHODS: Case report. RESULTS: We saw a 34-year-old women with oculo-dento-digital syndrome. Visual acuity was no perception of light (RE) and 1/35 (LE). Biomicroscopy revealed a flat anterior chamber and an advanced cataract. The intraocular pressure (IOP) was 60 mmHg in both eyes. Ultrasonographic biomicroscopy demonstrated a closed chamber angle in both eyes. Measurements of the axial length and of the diameter of the lens were 18.7 mm/6.0 mm for the RE and 18.7 mm/5.8 mm for the LE respectively. In the time following we conducted a cyclodestructive procedure in the RE and a cataract extraction with implantation of an intraocular lens in the LE. This led to a considerable reduction of the IOP in the RE and combined with local therapy to IOP regulation in the LE. CONCLUSION: In this patient nanophthalmos, cataract and spherophakia led to angle-closure glaucoma in both eyes. We recommend early monitoring of IOP, axial length and lens diameter. This case demonstrates that an early cataract extraction might beneficially influence the natural course of the disease.

Phosphorylation of Marburg virus VP30 at serines 40 and 42 is critical for its interaction with NP inclusions.

The Marburg virus (MBGV) nucleocapsid complex is composed of four viral proteins (NP, L, VP35, and VP30) and the negative-strand nonsegmented genomic RNA. NP, L, and VP35 are functionally conserved among the order Mononegavirales, whereas VP30, a phosphoprotein, represents a filovirus-specific nucleocapsid protein. In the present paper, we have characterized the localization and function of VP30 phosphorylation. The main phosphorylation sites are represented by seven serine residues in the region of amino acid 40 to 51 of VP30. Additionally, trace amounts of phosphothreonine were detected. Substitution of serine residues 40 and 42 by alanine abolished the interaction of VP30 with NP-induced inclusion bodies, which contain nucleocapsid-like structures formed by NP. Substitution of the other phosphoserine residues had little effect on this interaction. Replacement of the introduced alanine residues 40 and 42 by aspartate restored the interaction between VP30 and the NP inclusions pointing to the importance of negative charges at these particular positions.

Intron-exon structure and gene copy number of a gene encoding for a membrane-intrinsic light-harvesting polypeptide of the red alga Galdieria sulphuraria.

Genes for light-harvesting proteins (lhc genes) of higher plants are well examined. However, little is known about the corresponding genes of algae, although this knowledge might give valuable information about the evolution of photosynthetic antennae. In the case of rhodophytes only two cDNA sequences from a single organism, Porphyridium cruentum, have been published. Here we describe an additional sequence from another species, the thermo-acidophilic red alga Galdieria sulphuraria. For the first time also a genomic sequence for a red algal lhc gene is presented. From a cDNA library of G. sulphuraria we isolated a clone containing an open reading frame for a protein of 302 amino acids with a deduced molecular mass of 33.86kDa. It shares major structural features with eukaryotic light-harvesting polypeptides. A proposed cleavage site between transit peptide and mature protein gives rise to a transit peptide of 119 amino acids and a mature protein of 183 residues. Hydropathy analysis suggests that the mature protein consists of three transmembrane helices. Several amino acid residues supposed to bind chlorophyll a and chlorophyll b in higher plants are conserved. The protein shows up to 69% identity and 81% similarity to the Porphyridium polypeptides in the transmembrane helices 1 and 3. Using oligonucleotides annealing in the regions of the start and stop codons of the gene as primers, a DNA sequence was amplified from nuclear G. sulphuraria DNA by PCR. Compared with the cDNA clone, this sequence contains five additional intervening DNA strings of 50-74bp length. Four of them show typical features of spliceosomal introns with GT-AG borders, and the fifth differs by starting with GC. Three of the supposed introns are located in similar positions as introns of higher plant light-harvesting proteins. Southern blotting and hybridization experiments indicate that G. sulphuraria contains at least three copies of this gene.

Not all peripheral immune stimuli that activate the HPA axis induce proinflammatory cytokine gene expression in the hypothalamus.

Administration of low doses of lipopolysaccharide (LPS) that do not disrupt the blood-brain barrier (BBB) results in the expression of interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF alpha) in the hypothalamus in parallel to stimulation of the hypothalamus-pituitary-adrenal (HPA) axis. This endocrine response is triggered by peripheral cytokines, and we recently obtained evidence that brain-borne IL-1 contributes to its maintenance. LPS preferentially stimulates cells of the macrophage lineage and B lymphocytes. The possibility that primarily stimulation of other types of peripheral immune cells also results in the expression of proinflammatory cytokines in the brain and in the activation of the HPA axis was investigated. Our results showed that, in contrast to LPS, administration of the superantigen staphylococcal enterotoxin B (SEB), which stimulates T cells by binding to appropriate V beta domains of the T-cell receptor, did not result in induction of IL-1 beta, IL-6, and TNF alpha expression in the hypothalamus. Furthermore, although IL-2 transcripts in the spleen were highly increased, expression of this gene was not detected in the brain. However, as with LPS, SEB administration also results in elevated levels of glucocorticoids in blood. Therefore, our data suggest that increased expression of proinflammatory cytokines in the brain is not a necessary step in the stimulation of the HPA axis by SEB.

Sympathetic innervation affects superantigen-induced decrease in CD4V beta 8 cells in the spleen.

The stimulation by superantigens of T cells expressing an appropriate V beta chain results in a strong proliferative response that is followed by a state of energy specific for the antigen used. This model was used to continue our studies on immunoregulatory host neuroendocrine responses. We have recently found that four days after administration of the superantigen staphylococcal enterotoxin B (SEB) into mice, that is, at an early stage of the anergic phase, the decrease in the percentage of splenic CD4V beta 8 was accompanied by a decrease in the splenic concentration of the sympathetic neurotransmitter noradrenaline (NA) as compared to vehicle-injected mice. No comparable changes were detected in the kidney. At this point, blood levels of NA, adrenaline, and corticosterone were comparable in SEB- and vehicle-injected mice. We have also found that the decrease in splenic CD4V beta 8 cells was not observed in animals that had been chemically sympathectomized prior to the administration of the superantigen. These results indicate that the sympathetic response induced by SEB may have immunoregulatory implications.