Impact of porous nanomaterials on inhibiting protein aggregation behaviour

Aggregation of intrinsically disordered as well as the ordered proteins under certain premises or physiological conditions leads to pathological disorder. Here we have presented a detailed investigation on the effect of a porous metallic (Au) and a non-metallic (Si) nanomaterial on the formation of ordered (fiber-like/amyloid) and disordered (amorphous) aggregates of proteins. Porous nanogold (PNG) was found to reduce the amyloid aggregation of insulin but does not have much impact on the lag phase in the aggregation kinetics, whereas porous nano-silica (PNS) was found both to decrease the amount of aggregation as well as prolong the lag phase of amyloid fiber formation from insulin. On the other hand, both the porous nanoparticles are found to decrease the extent of amorphous aggregation (with slight improvement for PNS) of pathogenic huntingtin (Htt) protein in Huntington''s disease cell model. This is a noted direct observation in controlling and understanding protein aggregation diseases which may help us to formulate nanotherapeutic drugs for future clinical applications.

Aggregation of intrinsically disordered as well as the ordered proteins under certain premises or physiological conditions leads to pathological disorder.     

Rapid GTP binding and hydrolysis by Gq promoted by receptor and GTPase-activating proteins

Receptor-promoted GTP binding and GTPase-activating protein (GAP)-promoted GTP hydrolysis determine the onset and termination of G protein signaling; they coordinately control signal amplitude. The mechanisms whereby cells independently regulate signal kinetics and signal amplitude are therefore central to understanding G protein function. We have used quench-flow kinetic methods to measure the rates of the individual reactions of the agonist-stimulated GTPase cycle for G(q) during steady-state signaling. G(q) and m1 muscarinic cholinergic receptor were co-reconstituted into proteoliposomes with one of two GAPs: phospholipase C (PLC)-beta1, the major G(q)-regulated effector protein, and RGS4, a GAP commonly thought to be an inhibitor of G(q) signaling. In this system, the rate constant for GAP-stimulated hydrolysis of Galpha(q)-bound GTP at 30 degrees C was 9-12 s(-1) for PLC-beta1 and 22-27 s(-1) for RGS4. These rates are 1,000- to 2,000-fold faster than in the absence of a GAP and far faster than measured previously. G(q) can thus hydrolyze bound GTP with deactivation half-times of 25-75 ms at 30 degrees C, commensurate with physiological rates of signal termination. GDP/GTP exchange, which reactivates G(q), was the principal rate-limiting step for the GTPase cycle and was also faster than previously thought. At physiological concentrations of GTP, exchange was limited by the rate of dissociation of GDP from the receptor-G(q) complex, with a maximal rate of 1.8 s(-1) at 30 degrees C. Comparison of activation and deactivation rates help explain how GDP/GTP exchange balance rapid GTP hydrolysis to maintain steady-state signal amplitude.     

Primary spinal epidural extraosseous Ewing’s sarcoma: Report of five cases and literature review

Ewing’s sarcoma is the most common malignant bone tumour occurring in children and adolescents and exists in two different clinicopathological entities: osseous Ewing’s sarcoma (OES) and extraosseous Ewing’s sarcoma (EES). Five cases of primary epidural EES are described, which presented with non‐specific symptoms leading to a long diagnostic delay. The median age at diagnosis was 22 years (range 13–36 years). The median diagnostic delay was 3 months. All patients had one or more neurological deficits. All underwent surgical exploration with a laminectomy and partial resection followed by adjuvant radiotherapy to a dose of 46–50 Gy and chemotherapy with VAC (vincristine, adriamycin and cyclophosphamide) alternating with ICE (ifosphamide, cisplatin and etoposide) for at least six cycles. The mean follow‐up period is 21.2 months (range 11–32 months). Four of the five patients achieved a complete remission and are disease free at the time of writing this report. Two patients have a residual neurological deficit – both having presented with long history of neurological deficit. Primary spinal epidural EES should be suspected whenever young patients present with back pain and/or radicular pain, have abnormal neurology and an extradural mass is demonstrated on MRI. Surgical excision followed by adjuvant radiotherapy (50 Gy) and combination chemotherapy (VAC alternating with ICE) achieved local and systemic control in these patients. A greater number of patients and longer follow up are required to evolve a generally accepted treatment policy for this aggressive but potentially curable malignancy.     

The use of a blood conservation device to reduce red blood cell transfusion requirements: a before and after study

Introduction  

Anaemia and the associated need for packed red blood cell (PRBC) transfusions are common in patients admitted to the intensive care unit (ICU). Among many causes, blood losses from repeated diagnostic tests are contributory.     

Dyspareunia in gynaecological practice

Dyspareunia is a form of sexual dysfunction that can significantly affect quality of life and cause relationship difficulties. It is a symptom of a variety of disease states with components of both physical and organic dysfunction. Obtaining a comprehensive sexual history in an outpatient setting requires a high level of professionalism. A systematic examination of the lower genital tract is necessary to rule out any obvious cause, though further investigations such as ultrasound infrequently provides additional information. Diagnostic laparoscopy is an invasive procedure that is of limited use in the first line investigation of dyspareunia but may help detect pelvic adhesions or endometriosis in those where this condition is suspected. Before embarking on a laparoscopy it is important for the patient to be aware of a management plan in the event that the laparoscopy is negative. There are data to suggest that empirical medical treatment after a clinical diagnosis of endometriosis is effective and has the advantage of avoiding any invasive procedures. Psychosexual causes are important to consider during the assessment of the patient experiencing dyspareunia.     

Laparoscopic salpingectomy and removal of Essure hysteroscopic sterilisation device: a case series

Objectives: Tubal sterilisation using Essure is a minimally invasive technique for permanent contraception, with high rates of patient satisfaction. However, some women subsequently choose removal of the inserts, due to side effects such as pelvic pain, abnormal bleeding, dyspareunia or allergic dermatitis. This case series presents the management of eight women who underwent laparoscopic removal of Essure inserts in conjunction with salpingectomy. We describe our surgical technique, its underlying principles and immediate surgical outcomes.

Methods: Eight patients were identified as having undergone removal of Essure inserts, via an electronic search of the surgical procedures database. A retrospective review of case records was undertaken. The primary outcome was safety and feasibility of the laparoscopic salpingectomy approach. Secondary outcome measures included implant fracture rate, operative time, blood loss and length of patient stay.

Results: All eight women were able to undergo laparoscopic salpingectomy and removal of the Essure inserts without the need for laparotomy or hysterectomy. There were no incidences of fracture or incomplete removal of the insert. Immediate postoperative recovery was uncomplicated in all eight women; the mean length of stay was 17?h. One patient had a small bowel serosal tear attributed to laparoscopic entry.

Conclusion: This case series suggests that laparoscopic salpingectomy for removal of Essure inserts is safe and feasible. We acknowledge that the numbers were small. However, consistent use of a laparoscopic approach in these eight patients indicates that this procedure is a feasible and suitable alternative to hysterectomy.     

Comparison of autologous in situ blood coagulum versus sutures for conjunctival autografting after pterygium excision

Our aim was to compare the efficacy and safety of autologous in-situ blood coagulum versus sutures for attaching conjunctival limbal autografts (CAG) among patients undergoing primary pterygium excision over a period of 1 year. Thirty-two eyes of 32 patients with primary pterygium were randomly divided in into two groups: group I (16 eyes) underwent CAG with 10-0 monofilament nylon sutures and group II (16 eyes) underwent CAG with patient’s own in-situ blood coagulum acting as bioadhesive or fixative followed by bandaging for 48 h. Patients were followed up postoperatively on the 2nd day, 1 week, 2 weeks, 4 weeks, and 12 months. All the surgeries were done by the same surgeon. Graft success, recurrence rate, operating time, patient comfort, graft retraction or any other complication were studied. The duration of surgery was significantly less (P < 0.001) in group II (mean duration 15 ± 2 min) than group I (mean duration 67 ± 2 min). Postoperative symptoms were fewer for group II than group I. Rate of recurrence was equal in both groups (one patient in each group, 6.25 %). But complications regarding graft failure and graft retraction were more common in group II (two patients, 12.5 %) than group I (one patient, 6.25 %); however, the difference was not statistically significant (Z = 0.61). Thus, autologous in-situ blood coagulum is a useful method for graft fixation in pterygium surgery with shorter operating time and less postoperative discomfort.