Aquaporin 1 regulates GTP-induced rapid gating of water in secretory vesicles

The swelling of secretory vesicles has been implicated in exocytosis, but the underlying mechanism of vesicle swelling remains largely unknown. Zymogen granules (ZGs), the membrane-bound secretory vesicles in exocrine pancreas, swell in response to GTP mediated by a G(alpha)i3 protein. Evidence is presented here that the water channel aquaporin-1 (AQP1) is present in the ZG membrane and participates in rapid GTP-induced vesicular water gating and swelling. Isolated ZGs exhibit low basal water permeability. However, exposure of granules to GTP results in a marked potentiation of water entry. Treatment of ZGs with the known water channel inhibitor Hg2+ is accompanied by a reversible loss in both the basal and GTP-stimulatable water entry and vesicle swelling. Introduction of AQP1-specific antibody raised against the carboxyl-terminal domain of AQP1 blocks GTP-stimulable swelling of vesicles. Our results demonstrate that AQP1 associated at the ZG membrane is involved in basal as well as GTP-induced rapid gating of water in ZGs of the exocrine pancreas.     

Conjunctival cicatrizing disease presenting with lacrimal obstruction

Patients with conjunctival cicatrizing disease may develop lacrimal obstruction. Little is published on lacrimal obstruction as the presenting feature of otherwise asymptomatic cicatrizing conjunctival disease. The records of all patients presenting between 1994 and 2015 with lacrimal obstruction found to have cicatrizing conjunctival disease were reviewed. Demographic details, clinical findings, disease progression and treatment were analyzed. Thirty-five patients (25 female), aged 43–91 years (median 74, mean 71.3 years) had epiphora and a mild conjunctival cicatrizing process. Nine patients had onset of epiphora after cataract surgery. All except one patient had obstruction of the proximal lacrimal system (punctum and/or canaliculus). In 14 cases, the obstruction was unilateral (both puncta or canaliculi), with one progressing to bilateral obstruction after 11 years. In 19, all 4 puncta or canaliculi were obstructed. Two patients had unilateral nasolacrimal duct obstruction; one developed contralateral canalicular obstruction 2 years later. Conjunctival biopsies were obtained in 19 of 35 cases (54%), and OCP immunohistochemistry was positive in 7/19 (37%). All other biopsies showed chronic inflammation. Two patients had lichen planus. In follow-up (range 0.1–11 years, mean 3.2 years), 2 patients’ conjunctival disease progressed mildly, and 3 progressed moderately, with 2 of these 5 having positive OCP immunohistochemistry, and 1 having lichen planus. Patients with conjunctival cicatrization may present with lacrimal obstruction, usually punctal or canalicular. Conjunctival disease is usually mild and non-progressive, but patients should be monitored for disease progression.     

Pre-marriage prevention of thalassaemia: report of a 100 000 case experience in Isfahan

Background: Iran like other middle east countries has a large number of major thalassaemics. Due to religious restrictions on abortion, the routine prevention of the birth of thalassaemic children by this means is not possible. The aim of this study is to describe an alternative means to prevent the birth of thalassaemic children.Methods: From January 1993 to January 1996, 100 000 people preparing for marriage were screened for the thalassaemia trait, using CBC and HbA₂ level measurement. High risk couples were referred for further consultation regarding the disease and the means of its prevention. The proposed actions of the couples regarding thalassaemia prevention were evaluated immediately after consultation and then re-evaluated three months later. Result: After the project had been running for three years the average of high risk couple initially deciding not to marry was 90% and no new cases of thalassemia were detected in the children of the screened population.Conclusion: Where both members of the couple were trait-positive their preferred choice was not to marry, rather than to marry and use other or no methods of preventing a thalassemia affected child being born to them. Cultural and religious ideas can affect such decisions and in some Islamic countries the establishment and use of a genetic counselling centre can help prevent most of new thalassaemia cases.     

A rationale for membrane peeling in the repair of stage 4 macular holes

AIM: To examine the histological and immunocytochemical characteristics of epiretinal membranes (ERM) associated with stage 4 macular holes (MH) so as to establish a vitreoretinal rationale for surgery in stage 4 MH. METHOD: Consecutive patients with stage 4 MH undergoing vitrectomy and membrane peeling were recruited. Preoperatively, the eyes were examined for ERM formation over the macula and completeness of posterior hyaloid membrane (PHM) separation from the retina. ERM peel specimens obtained during surgery were sent for histological and immunocytochemical studies and were compared with the PHM specimens taken from a previous post-mortem study of eyes with physiological posterior vitreous detachment but without macular holes. RESULT: A total of 13 patients with stage 4 MH fulfilled the inclusion criteria and were recruited. Preoperatively, all eyes had an ERM over the macula and incomplete separation of the PHM seen as a defect in the PHM on specular biomicroscopy. Histologically, the ERM specimens had very similar morphological characteristics to PHM, consisting of an eosinophilic membrane of varying thickness with scattered spindle-shaped cells. The membranes stained positively for type IV collagen while the cells were glial fibrillary acidic protein positive. Postoperatively, successful closure of MH was achieved in all cases. CONCLUSION: Stage 4 MH is characterised by incomplete separation of the PHM from the retina with remnants overlying the macula manifesting as ERM. Removal of the ERM is required during vitrectomy in order to relieve the tangential forces involved in the development of MH.