Cerebroprotective Potential of Hesperidin Nanoparticles Against Bilateral Common Carotid Artery Occlusion Reperfusion Injury in Rats and In silico Approaches

Neurotoxicity Research - Cerebral ischemia-reperfusion (C I/R) accelerates neuronal injury through the overproduction of reactive oxygen species due to mitochondrial dysfunction. Hesperidin has...     

Decrease in Antioxidant Status of Plasma and Erythrocytes from Geriatric Population

Background: Ageing is associated with an accumulation of free radical damage, which leads to physiological and clinical modifications. The study aims to find out the status of lipid profile, antioxidant enzymes, malondialdehyde in geriatric population. Patients/methods: The study was conducted on 150 subjects (75 healthy control between the ages of 20–30 years and 75 elderly subjects between ages of 50–70 years as cases). The following parameters were analyzed using the standard reference methods: lipid profile, reduced glutathione, glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase and malondialdehyde. Results: The present study was conducted to estimate the oxidative stress parameters in geriatric population. Highly significant increase in total cholesterol (TC), triglyceride (TG), LDL-cholesterol (LDL-C), VLDL-cholesterol (VLDL-C), malondialdehyde, catalase and decrease in high density lipoprotein cholesterol (HDL-C), reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase was observed in geriatrics when compared with their younger counterparts. Conclusion: This study concluded that there is enhanced oxidative stress and decreased antioxidant defence in geriatrics as compared to younger subjects which could play an important role in ageing. Dyslipidemia has become one of the important risk factors for the increasing prevalence of cardiovascular diseases. There is lack of awareness on the relationship between blood lipids and the risk of cardiovascular diseases in geriatric population. The strategy of early prevention should be adopted against dyslipidemia.     

Stem cell transplantation in rheumatoid arthritis

The therapeutic potential of high dose cytotoxic therapy and stem cell transplantation (SCT) in severe rheumatoid arthritis (RA) was originally supported by animal studies and serendipitous clinical cases where allogeneic and autologous procedures were shown to ameliorate and potentially cure the disease. Phase I and Phase II clinical studies established the feasibility, safety and efficacy of autologous stem cell mobilisation and transplantation. Although it was clear that the effects of high dose chemotherapy and autologous SCT could safely achieve profound responses, sustained control of disease usually required the reintroduction of disease modifying agents. Responses were improved with dose escalation of the conditioning regimen, and also with post-SCT therapy, such as rituximab, but were not observed with graft manipulation. Phase III studies were attempted, but recruitment was compromised by the increasingly widespread use of biological anti-rheumatic agents. Autologous SCT is now only reasonably considered in relatively rare patients whose disease has resisted conventional and biological treatments, and small numbers of cases continue to be registered with the EBMT. Occasional patients treated with allogeneic and syngeneic SCT continue to stimulate academic interest, particularly as some appear to be cured, but significant logistical and toxicity issues mean that routine and widespread application is unrealistic. In summary, SCT continues to have a limited therapeutic potential in rare patients with RA refractory to modern therapy and sufficient fitness for the procedure. From a scientific perspective, ablation of the dysfunctional rheumatoid immune system and its reconstruction with SCT has provided useful insights into the pathophysiology of RA.     

Outcomes and treatments of patients with immunoglobulin light chain amyloidosis who progress or relapse postautologous stem cell transplant

Immunoglobulin light chain (AL) Amyloidosis is a condition whereby misfolded proteins generated by plasma cells deposit in tissues causing organ dysfunction. Chemotherapy and autologous stem cell transplant when eligible are standard treatment options. Several studies report long‐term outcomes of patients post‐transplant. However, there is a paucity of literature describing outcomes of relapsed patients post‐transplant. We performed a retrospective study to assess outcomes and therapies employed upon relapse after transplant. Between 1996 and 2009, 410 patients received transplant at the Mayo Clinic as first‐line therapy. Of those patients, 42 (10%) died within 3 months of transplant, 64 (16%) died without documented relapse, 158 (38%) were alive without documented progression, and 146 (36%) had documented progression. Those 146 patients are the subject of our study, and their median time to hematologic relapse/progression was 23.6 months (95%CI 18.3, 26.3 months). Their median overall survival and 5‐yrs overall survival from post‐transplant relapse/progression was 51.7 months (95%CI 34.1–62.3) and 39%, respectively. The most common first regimen for treatment after relapse was lenalidomide or thalidomide. In conclusion, our study indicates that patients with AL amyloidosis fare well post‐transplant relapse/progression. Additionally, it provides a yardstick to design clinical trials to determine best treatment options.     

Efficacy and safety of tenecteplase in pulmonary embolism

Pulmonary embolism (PE) is a relatively common life-threatening cardiovascular condition associated with significant morbidity and mortality. We present the efficacy and safety data of weight-adjusted tenecteplase in 30 consecutive patients of acute PE. 30 patients (22 male, 8 female) with acute PE were included in the study and divided into three groups: (1) Acute PE complicated by shock stage and/or persistent hypotension (12 patients). (2) RV dilatation and/or dysfunction without hypotension (14 patients). (3) Severe hypoxemia without hypotension and RV dysfunction (4 patients). Predominant symptoms were dyspnoea, cough, chest pain, syncope and haemoptysis, noted in 100 % (30), 40 % (12), 54 % (16), 32 % (9) and 10 % (3) of patients respectively. RV dilatation and dyskinesia were present in 86 %, septal paradoxical movement in 73 % and inferior venacava collapse absent in 53 % of patients respectively. 12 patients presented with acute PE and cardiogenic shock, 14 patients showed RV dilatation and dysfunction with systolic BP >90 mmHg and four patients were having RV dilation without dysfunction but severe hypoxemia. There was significant reduction in right ventricular systolic pressure and improvement in right ventricular dysfunction. Our study shows that tenecteplase is very effective and safe in the treatment of PE with minimal risk of bleeding in high risk group and intermediate risk and even in selective low risk category group of patients. However, in view of small number of patients in study group, a large multicentre randomized study would be required to draw a firm conclusion regarding the thrombolysis in low risk category patient.     

Development of a species-specific colorimetric-PCR assay for detection and species differentiation of Mycobacterium immunogenum and Mycobacterium chelonae and its comparison with quantitative real-time PCR for field metalworking fluids

Mycobacterium immunogenum and Mycobacterium chelonae are closely related species associated with occupational hypersensitivity pneumonitis (HP) and nosocomial infections. There is a need to develop specific and readily adaptable methods for detection and speciation of these agents. Here we report development of a probe-based colorimetric-PCR assay involving heat shock protein (hsp) gene amplification (228bp) and its detection in an ELISA-like reaction. A quantitative format of this assay was developed and validated on metalworking fluids (MWF). The assay showed a minimum detection limit of 10 fg genomic DNA or 1 mycobacterial cell, albeit with variations depending on type and composition of the MWF matrix. When applied to the field MWF samples, the developed assay was found to be comparable to the real-time PCR assay, and allowed direct speciation of MWF mycobacteria without sequencing and/or restriction pattern analysis. In conclusion, the developed colorimetric PCR allows detection and quantification of MWF mycobacteria without culturing and is the first probe-based assay for unambiguous differentiation between the two phylogenetically closely related species, M. immunogenum and M. chelonae. Considering that the assay offers high throughput format involving relatively simpler instrument infrastructure, it has a potential for applications in routine assessment of MWF mycobacteria in diagnostic and industrial laboratories.     

Permanent-temporary pacemakers in the management of patients with conduction abnormalities after transcatheter aortic valve replacement

Background

Damage to the cardiac conduction system requiring permanent pacemaker (PPM) implantation is a known adverse outcome of transcatheter aortic valve replacement (TAVR). A permanent-temporary pacemaker (PTPM) is a device that involves an active-fixation lead attached to an external pulse generator taped to the skin. We reviewed the utility of PTPMs as a temporary bridge measure after TAVR in patients with conduction abnormalities that do not meet conventional criteria for PPM placement.

Methods

Between January 01, 2013 and December 31, 2015, we analyzed 67 patients who received PTPM after TAVR. Baseline demographics, comorbidities, type and size of the valve, pre-TAVR electrocardiograms (ECGs), post-TAVR ECGs at 1 day, 1 month, and 6 months, and pacemaker interrogation results were reviewed for each patient if available.

Results

The mean age of patients was 80.5?±?9.1 years. PTPM were placed for 2.3?±?2.4 days. Among these patients, 44.8% (n?=?30) received a PPM prior to discharge. Male gender (OR 2.84, 95% CI 1.05–7.69, p?=?0.05) and an increase in QRS duration post-TAVR (p?=?0.01) were associated with PPM placement. Pacemaker interrogation data of 11 patients with PPM revealed that 27% (n?=?3) had <?1% V-pacing requirements and <?10% A-pacing requirements.

Conclusions

In post-TAVR patients who develop conduction abnormalities that do not meet conventional PPM implantation indications, PTPM safely provides a time period for further assessment and may prevent unnecessary PPM implantation. Male gender and an increase in QRS duration post-TAVR are associated with PPM implantation. Additionally, some patients may recover from their conduction disturbances and demonstrate low pacemaker utilization.