New approaches for diagnosis of dry eye disease

We reviewed the literature for different diagnostic approaches for dry eye disease (DED) including the most recent advances, contradictions and promising diagnostic tools and technique. We performed a broad literature search for articles discussing different methods for diagnosis of DED including assessment of tear osmolarity, tear film stability, ocular biomarkers and others. Articles indexed in PubMed and google scholar were included. With the growing cosmetic industry, environmental pollution, and booming of digital screens, DED is becoming more prevalent. Its multifactorial etiology renders the diagnosis challenging and invites the emergence of new diagnostic tools and tests. Diagnostic tools can be classified, based on the parameter they measure, into tear film osmolarity, functional visual acuity, tear volume, tear turnover, tear film stability, tear film composition, ocular biomarkers and others. Although numerous methods exist, the most accurate diagnosis can be reached through combining the results of more than one test. Many reported tests have shown potential as diagnostic/screening tools, however, require more research to prove their diagnostic power, alone or in combination. Future research should focus on identifying and measuring parameters that are the most specific to DED diagnosis.     

Effects of body position on transient evoked otoacoustic emissions: the clinical perspective Efectos de la posición del cuerpo en las emisiones otoacústicas evocadas por transitorios: la perspectiva clínica

The present study investigated body position effects on transient evoked otoacoustic emission (TEOAE) recordings of clinical significance. Sixty adults (30 males, 30 females) were assessed using the Otodynamics ILO88 Analyzer in three positions (sitting, supine, and side-lying). Results indicated significant positional effects on the TEOAE parameters of A–B difference, noise, whole wave reproducibility, and response levels. These differences included higher noise levels in supine and side-lying positions in comparison to the upright sitting position. Lower whole wave reproducibility measurements, and higher response amplitudes, in the side-lying position compared with supine and seated positions were also observed. No significant effects were evident for signal-to-noise ratio or band reproducibility. Given the lack of significant body position effects on these latter parameters and the infrequent clinical use of the other parameters in isolation, there was no evidence to suggest the future need for major review of current pass/fail criteria or of the standard test protocol.     

Endotoxin-induced cytokine and chemokine expression in the HIV-1 transgenic rat

Background  

Repeated exposure to a low dose of a bacterial endotoxin such as lipopolysaccharide (LPS) causes immune cells to become refractory to a subsequent endotoxin challenge, a phenomenon known as endotoxin tolerance (ET). During ET, there is an imbalance in pro- and anti-inflammatory cytokine and chemokine production, leading to a dysregulated immune response. HIV-1 viral proteins are known to have an adverse effect on the immune system. However, the effects of HIV-1 viral proteins during ET have not been investigated.     

Acute,sub-acute and general pharmacological evaluation of 5-(3,4-methylenedioxyphenyl)-4-ethyl-2E,4E-pentadienoic acid piperidide (SK-20): A novel drug bioavailability enhancer

An efflux pump inhibitor, SK-20 (5-(3,4-methylenedioxyphenyle)-4 ethyl-2E,4E-pentadienoic acid piperidide), was assessed for its toxicity at three different pharmacological profiles: acute, sub-acute and general pharmacology with pharmacokinetics. In acute study, the SK-20 was found safe up to a dose of 2000 mg/kg (b.wt.); and at sub-acute, dosages of 50 and 100 mg/kg (b.wt.) were found to be safe. However, dosages of 200 mg or above per kg (b.wt.) showed some morphological alterations in cellular architecture of both liver and kidneys in both sexes, viz., mild vascular congestion along with sporadic hemorrhages and infiltration into renal and hepatic parenchyma by mononucleate cell. General pharmacological studies did not result into any alterations in analgesic, convulsions, rectal temperatures and in the rhythm or the rate of the intestinal motility or the secretion of the bile. While the respiratory and the cardiac rate remained normal, the only parameter to show was the blood pressure, which at all the doses tested, showed a tendency toward reduction. Characteristically, the SK-20 at all doses influenced pentobarbital-induced hypnosis positively and negatively to spontaneous motor activity in a dose dependent manner. Pharmacokinetics of SK-20 revealed it to have retention time at 10.2 min and half life 2.47 h.     

Left Main Coronary Artery Thrombosis With Acute Myocardial Infarction: A Management Dilemma

Left main coronary artery (LMCA) thrombosis with acute myocardial infarction is a rare condition with very high mortality. The low incidence of this condition and exclusion of patients with LMCA thrombosis from clinical trials prevent the development of optimal management strategy in these patients. Therefore, there are no clear-cut guidelines describing an evidence-based approach for this condition. We describe a patient with LMCA thrombosis presenting with acute myocardial infarction, who was found to have hypercoagulable state related to homocysteinemia on further work-up. This case highlights the challenges faced during the management of this rare condition due to lack of clear-cut guidelines describing an evidence-based approach.     

A Phase II Study of Biodegradable Stents Plus Palliative Radiotherapy in Oesophageal Cancer

AimsSelf-expanding metal stents provide rapid improvement of dysphagia in oesophageal cancer but are associated with complications. The aim of the present study was to test the effectiveness of an alternative treatment of combining biodegradable stents with radiotherapy.Materials and methodsA Simon two-stage single-arm prospective phase II trial design was used to determine the efficacy of biodegradable stents plus radiotherapy in patients with dysphagia caused by oesophagus cancer who were unsuitable for radical treatment. Fourteen patients were recruited and data from 12 were included in the final analyses.ResultsFive of 12 patients met the primary end point: one stent-related patient death; four further interventions for dysphagia within 16 weeks of stenting (41.7%, 95% confidence interval 15.2–72.3%). The median time to a 10-point deterioration of quality of life was 2.7 weeks. Nine patients died within 52 weeks of registration. The median time to death from any cause was 15.0 weeks (95% confidence interval 9.6–not reached).ConclusionThe high re-intervention observed, which met the pre-defined early stopping criteria, meant that the suggested alternative treatment was not sufficiently effective to be considered for a larger scale trial design. Further work is needed to define the place of biodegradable stents in the management of malignant oesophageal strictures.     

Proteasome inhibition leads to early loss of synaptic proteins in neuronal culture

A dysfunctional ubiquitin proteasome system may be a mediating factor of disease progression in Lewy body dementia (LBD). The effects of proteasome inhibition using lactacystin and epoxomicin in primary neuronal culture were studied to assess the validity of this model to reflect the cortical pathology of LBD. Treatment of primary cortical neurons with 5???M lactacystin for 24?h led to a 38?% reduction in the levels of ??-III-tubulin (p?<?0.05), a 48?% reduction in the levels of synaptophysin (p?<?0.05) and a 74?% reduction in the levels of drebrin (p?<?0.01), when compared to controls. Results for epoxomicin were similar. The loss of neuronal protein occurred prior to any loss of mitochondrial activity or cell death. The results are reflective of the loss of synapses and the synaptic changes observed in LBD, which may be an early event in the neurodegeneration of LBD. The similarities with the pathological changes in LBD highlight the possibility that this model can potentially provide a platform to test novel treatments.