Interaction of aristolochic acid with Vipera russelli phospholipase A2: its effect on enzymatic and pathological activities

Aristolochic acid, an alkaloid from the plant Aristolochia species, interacts with the major basic phospholipase A2 from Vipera russelli venom. It is an uncompetitive inhibitor with a Ki of 9.9 X 10(-4)M when phosphatidylcholine is used as substrate. The inhibition of direct and indirect hemolysis is higher compared to the inhibition of phosphatidylcholine hydrolysis. Edema-inducing activity of Vipera russelli phospholipase A2 is inhibited by aristolochic acid when injected either as a mixture or separately. Both i.m. and i.p. administration of aristolochic acid following phospholipase injection are equally effective in inhibiting edema. The alkaloid inhibits the edema-inducing activity as soon as it reaches the site, but does not aid in recovery. Aristolochic acid failed to inhibit other pathological activities of the enzyme.     

双相恶性子宫肿瘤:一例报道及文献复习(英文)

We present a rare case of a 50-year old lady who presented with pain abdomen and bleeding per vaginum of 3 months duration. Per vaginal examination revealed an exophytic growth arising from vault. Histopathological examination of the vault biopsy showed malignant neoplasm with features suggestive of carcinosarcoma of vault with immunohistochemistry showing stromal cells positive for CD10 and negative for SMA. Ki67 index was 40%-50%. She received external beam radiotherapy to pelvis 50.4 Gy/25 fractions but did not respond to the same. The lesion was not surgically resectable and hence referred to the division of medical oncology for chemotherapy. She was started on ifosphamide with cisplatin with growth factor support. It was planned to do a reassessment after 3 cycles of chemotherapy, but patient succumbed to the illness.     

Isolated Pupil-Involving Third Nerve Palsy as the First Presentation of Sarcoidosis

Neurosarcoidosis is seen in 5–15% of patients with systemic sarcoidosis. The most common cranial nerve presentations are optic neuropathy and facial nerve palsy. The authors present a case of sarcoidosis presenting with a pupil-involving third nerve palsy. The patient responded to corticosteroid therapy with resolution of investigations her cranial nerve palsy but progressed to develop cerebellar signs. This is the first documented case of a pupil-involving third nerve palsy occurring as the first presentation of neurosarcoidosis. Although typically a pupil-involving third nerve palsy necessitates urgent neuroimaging to rule out a posterior communicating artery aneurysm, it is important to recognise inflammatory causes in the differential diagnosis.     

Triple Leads Programmed to Perform as Longitudinal Guarded Cathodes in Spinal Cord Stimulation: A Modeling Study

Objective: In spinal cord stimulation, neurosurgeons increasingly tend to implant dual leads. Dual leads (longitudinal bipole/tripole) provide medio‐lateral control over the recruited dorsal column (DC) area by steering the injected cathodal currents. However, the DC recruited area is suboptimal when dual aligned leads straddling the midline programmed as longitudinal guarded cathodes (+−+) are used instead of a single lead placed over the spinal cord midline with the same configuration. As a potential improvement, an additional third lead between the two aligned leads is modeled to maximize the medio‐lateral extent of the DCs at the low‐thoracic vertebral region (T10‐T12). Methods and Materials: The University of Twente Spinal Cord Stimulation software (UT‐SCS) is used in this modeling study. Longitudinal guarded cathodes were modeled on the low‐thoracic vertebral region (T10‐T12) using percutaneous triple lead configurations. The central lead was modeled over the spinal cord midline and the two lateral leads were modeled at several transverse distances to the midline lead. Medio‐lateral field steering was performed with the midline lead and the second lead on each side to achieve constant anodal current ratios and variable anodal current ratios. Results: Reducing the transverse lead separation resulted in increasing the depths and widths of the recruited DC area. The triple lead configuration with the least transverse separation had the largest DC recruited area and usage range. The maximum DC recruited area (in terms of both depth and width) was always found to be larger under variable anodal current ratio than constant anodal current ratio conditions. Conclusions: Triple leads programmed to perform as longitudinal guarded cathodes provide more postoperative flexibility than single and dual leads in covering a larger width of the low‐thoracic DCs. The transverse separation between the leads is a major determinant of the area and distribution of paresthesia.     

Prevalence and predictors of delayed gastric emptying among Indian patients with long-standing type 2 diabetes mellitus

Background and Aims

Upper gastrointestinal symptoms are more prevalent among type 2 diabetes mellitus (T2DM) patients. The prevalence of delayed gastric emptying (GE) and factors predictive of it have not been studied in Indian T2DM patients and the present study aimed to study the same.

Methods

This hospital-based cross-sectional study involved adult (age between 18 and 65 years) outpatients with T2DM of ≥5-year duration. Measurements of GE of a labelled standardized solid rice idli meal by gastric emptying scintigraphy (GES), symptoms of delayed GE (by standardized questionnaire) and autonomic function by cardiovascular autonomic function tests (AFTs) were carried out. Thirty healthy subjects served as controls for GES and AFTs.

Results

One hundred and forty T2DM patients (age range: 32–65 years) were studied. Delayed GE was documented in ≈29 % (40/140) and rapid GE in 2 % (3/140) of T2DM patients. Univariate analysis showed significant positive association between delayed GE and duration of DM, body mass index (BMI), HbA1c, retinopathy, peripheral neuropathy, autonomic dysfunction and coronary artery disease (p < 0.05 for all). However, there was no significant correlation of age, sex, symptoms suggestive of gastroparesis and nephropathy with delayed GE. Hypoglycemic episodes were significantly more frequent in those with delayed GE (p < 0.05). Multiple logistic regression analysis revealed only BMI and HbA1c to be significant independent predictors of delayed GE.

Conclusion

Presence and severity of symptoms of gastroparesis did not predict delayed GE. Delayed GE, irrespective of symptoms, was associated with microvascular and macrovascular diabetic complications and increased risk of hypoglycemic episodes. HbA_1c and BMI were independent predictors of delayed GE.

     

Local thermal injury elicits immediate dynamic behavioural responses by corneal Langerhans cells

Langerhans cells (LCs) represent a special subset of immature dendritic cells (DCs) that reside in epithelial tissues at the environmental interfaces. Although dynamic interactions of mature DCs with T cells have been visualized in lymph nodes, the cellular behaviours linked with the surveillance of tissues for pathogenic signals, an important function of immature DCs, remain unknown. To visualize LCs in situ, bone marrow cells from C57BL/6 mice expressing the enhanced green fluorescent protein (EGFP) transgene were transplanted into syngeneic wild-type recipients. Motile activities of EGFP(+) corneal LCs in intact organ cultures were then recorded by time lapse two-photon microscopy. At baseline, corneal LCs exhibited a unique motion, termed dendrite surveillance extension and retraction cycling habitude (dSEARCH), characterized by rhythmic extension and retraction of their dendritic processes through intercellular spaces between epithelial cells. Upon pinpoint injury produced by infrared laser, LCs showed augmented dSEARCH and amoeba-like lateral movement. Interleukin (IL)-1 receptor antagonist completely abrogated both injury-associated changes, suggesting roles for IL-1. In the absence of injury, exogenous IL-1 caused a transient increase in dSEARCH without provoking lateral migration, whereas tumour necrosis factor-alpha induced both changes. Our results demonstrate rapid cytokine-mediated behavioural responses by LCs to local tissue injury, providing new insights into the biology of LCs.