Laser therapy of muscle injuries

Low-level lasers are used in general therapy and healing process due to their good photo-bio-stimulation effects. In this paper, the effects of diode laser and Nd:YAG laser on the healing process of practically managed skeletal muscle trauma has been successfully studied. Standard impact trauma was induced by using a specially designed mechanical device. The impacted muscle was left for 3 days for complete development of blunt trauma. After that it was irradiated by five laser sessions for 5 days. Two types of lasers were used; 785-nm diode laser and 1.064-nm Nd:YAG laser, both in continuous and pulsed modes. A special electronic circuit was designed and implemented to modulate the diode laser for this purpose. Tissue samples of crushed skeletal muscle have been dissected from the injured irradiated muscle then bio-chemically analyzed for the regeneration of contractile and collagenous proteins using Lowry assay for protein determination and Reddy and Enwemeka assay for hydroxyproline determination. The results showed that both lasers stimulate the regeneration capability of traumatized skeletal muscle. The diode laser in CW and pulsed modes showed better results than the Nd:YAG in accelerating the preservation of the normal tissue content of collagenous and contractile proteins beside controlling the regeneration of non-functional fibrous tissue. This study proved that the healing achieved by the laser treatment was faster than the control group by 15–20 days.     

Biological and clinical relevance of stem cells in pancreatic adenocarcinoma

Cancer stem cells (CSC) have been identified in a growing number of human malignancies. CSC are functionally defined by their ability to self-renew and recapitulate tumors in the ectopic setting, and a growing number of studies have shown that they display other functional characteristics, such as invasion and drug resistance. These unique functional properties implicate a role for CSC in clinical consequences, such as initial tumor formation, relapse following treatment, metastasis, and resistance, suggesting they are a major factor in directing clinical outcomes. Pancreatic adenocarcinoma is a highly-aggressive disease with a propensity for early metastasis and drug resistance. Tumorigenic pancreatic cancer cells have been identified using the cell surface antigens CD44, CD24, and CD133, as well as the high expression of aldehyde dehydrogenase (ALDH). In vitro and in vivo studies have shown that ALDH- and CD133-expressing pancreatic CSC have a greater propensity for metastasis, and ALDH-expressing CSC have been shown to be resistant to conventional chemotherapy. In clinical samples from patients with resected pancreatic adenocarcinoma, the presence of ALDH-expressing CSC was associated with worse overall survival. The development of CSC-targeting therapies might be important in changing the clinical outcomes of patients with this disease, and others and we have begun to identify novel compounds that block CSC function. This review will discuss the biological and clinical relevance of CSC in pancreatic cancer, and will discuss novel therapeutic strategies to target them.     

Delayed left main stem obstruction following successful TAVI with an Edwards SAPIEN XT valve: successful resuscitation and percutaneous coronary intervention using a non-invasive automated chest compression device (AutoPulse)

Acute coronary artery obstruction at the time of device implantation is a recognized, albeit rare, complication of TAVI and is most frequently managed by emergency percutaneous intervention. This complication usually manifests with circulatory collapse due to compromising left ventricular ischemia and is most often observed immediately following valve deployment in the catheter laboratory or in theater. Immediate circulatory support is often necessary. We describe the first report of delayed left main stem obstruction 3.5 hours after successful deployment of a 26 mm Edwards SAPIEN XT valve via transfemoral implantation, with sudden development of circulatory collapse on the ward. Circulatory support was rapidly and effectively instituted with an automated non-invasive cardiac massage device, AutoPulse, that delivers continuous chest compressions. Successful emergency percutaneous intervention was then undertaken to the left main stem to displace a calcified nodule during automated external cardiac massage with the AutoPulse.     

A disintegrin and metalloprotease (ADAM) 33 protein in patients with pulmonary sarcoidosis

Background and objective: A disintegrin and metalloproteinase (ADAM) 33 is a susceptibility gene associated with inflammatory lung and skin diseases. It is selectively expressed in mesenchymal cells, and its metalloprotease activity has been linked to angiogenesis and tissue remodelling. A soluble form of ADAM33 (sADAM33) has been identified in the bronchoalveolar lavage fluid (BALF) of asthmatic patients, and its levels inversely correlate with lung function. Because of its association with inflammatory lung diseases, it was hypothesized that sADAM33 is elevated in BALF of patients with pulmonary sarcoidosis. Methods: After removal of Ig using Protein A/G and enrichment using Concanavalin A beads, sADAM33 was identified in BALF by Western blotting. A fluorescence resonance energy transfer peptide cleavage assay was used to assess ADAM33‐like activity in BALF. Results: sADAM33 protein in BALF was detected as a 25 kDa fragment, and levels were significantly increased in samples from sarcoid patients when compared to healthy controls (P < 0.05). Levels of sADAM33 were inversely correlated with lung function (FVC%) (P < 0.05) and DL_CO % predicted (P < 0.01). No difference in sADAM33 enzymatic activity was observed between healthy and sarcoid BALF samples. Conclusions: Release of sADAM33 is increased in sarcoid and may be associated with abnormal lung function. sADAM33 may be a biomarker of lung tissue inflammation and remodelling in sarcoid.     

Nocturnal Medications Dosing: Does It Really Make a Difference in Blood Pressure Control Among Patients with Chronic Kidney Disease?

Ambulatory blood pressure (BP) monitoring is superior to clinic BP monitoring in predicting long-term consequences of hypertension. This has raised interest in diurnal variation in BP and elevation in nighttime BP as a prognostic and therapeutic target. Several studies have identified prevalence of nocturnal hypertension in patients with accelerated progression of chronic kidney disease and target organ damage. Some studies suggest that nocturnal BP can be lowered by changing administration of antihypertensive medication to bed time; whether that results in retarding kidney disease progression is not very clear. Further research is needed to determine if certain classes of medications or interventions are superior in controlling nocturnal hypertension, and protocols need to be developed to screen patients for monitoring nocturnal BP. Further studies are needed to evaluate long-term renal outcomes of evening dosing in patients with nocturnal hypertension and chronic kidney disease.     

Synthesis,acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities,and molecular docking studies of a novel compound based on combination of flurbiprofen and isoniazide

Synthesis of a compound with balanced bioactivities against a specific target is always a challenging task. In this study, a novel compound (1) has been synthesized by combination of flurbiprofen and isoniazide and shows ∼2.5 times enhanced acetylcholinesterase (AChE) inhibition activity and ∼1.7 times improved butyrylcholinesterase (BuChE) inhibition activity compared to flurbiprofen and a standard drug (i.e. physostigmine). A comparative AutoDock study has been performed, based on the optimized structure, by the DFT/B3LYP method, which confirmed that compound (1) is more active against AChE and BuChE, with calculated binding energies of −12.9 kcal mol⁻¹ and −9.8 kcal mol⁻¹ respectively as compared to flurbiprofen and an eserine (physostigmine) standard for which the binding energy was calculated to be −10.1 kcal mol⁻¹ and −8.9 kcal mol⁻¹, respectively. A mixed mode of inhibition of AChE and BuChE with compound 1 was confirmed by Lineweaver–Burk plots. AChE and BuChE inhibition activity alongside docking results suggests that compound (1) could be used for treatment of Alzheimer''s disease. Moreover, compound (1) also exhibit better α-chymotrypsin activity compared to flurbiprofen. Furthermore, in vitro and in vivo analysis confirmed that compound (1) exhibit more activity and less toxicity than the parent compounds.

A novel compound (1) shows ∼2.5 and ∼1.7 times enhanced AChE inhibition activity and BuChE inhibition activity respectively compared to flurbiprofen and standard drug (i.e. physostigmine). It has also been confirmed by comparative AutoDock studies.     

Large interlayer spacing Nb4C3Tx (MXene) promotes the ultrasensitive electrochemical detection of Pb2+ on glassy carbon electrodes

A Nb₄C₃T_x (MXene)-modified glassy carbon electrode was used for the electrochemical detection of Pb²⁺ ions in aqueous media. The sensing platform was evaluated by anodic stripping analysis after optimizing the influencing factors such as pH, deposition potential, and time. The large interlayer spacing, high c lattice parameter and higher conductivity of Nb₄C₃T_x compared to other MXenes enhance the electrochemical detection of Pb²⁺. The developed sensor can reach a detection limit of 12 nM at a potential ∼−0.6 V. Additionally, the developed sensor showed promising selectivity in the presence of Cu²⁺ and Cd²⁺, and stability for at least 5 cycles of continuous measurements with good repeatability. This work demonstrates the potential applications of Nb₄C₃T_x towards the development of effective electrochemical sensors.

Large interlayer spacing Nb₄C₃T_x (MXene) promotes the ultrasensitive electrochemical detection of Pb²⁺ on glassy carbon electrodes     

Evaluation of Hemodynamic Changes Using Different Intra-Abdominal Pressures for Laparoscopic Cholecystectomy

Biliary diseases known since ages constitute major portion of digestive tract disorders world over. Among these cholelithiasis being the fore runner causing general ill health, thereby requiring surgical intervention for total cure. The study was undertaken in an attempt to compare the hemodynamic changes in patient undergoing laparoscopic cholecystectomy using different intra-abdominal pressures created due to carbon dioxide insufflation. The patients were randomly allocated to one of the three groups in which different levels of intra-abdominal pressures (8–10 mmHg,11–13 mmHg and 14 mmHg and above) were maintained. The base line parameters monitored were heart rate, non invasive blood pressur(systolic and mean)and end tidal carbon dioxide. All the parameters were monitored at various intervals i.e. Immediately during insufflation, 5 min, 10 min, 20 min, 30 min after CO2 insufflation and after every 10 min if surgery exceeds 30 min, at exsufflation,10 min after CO2 exsufflation. Patients were ventilated with Pedius Drager Ventilator keeping tidal volume 8–10 ml/kg and respiratory rate 12–14 breaths/min. During surgery patients were placed in reverse Trendlenburg position (head up) at 15 °. The results obtained were evaluated statistically and analyzed. Baseline characteristics were found to be comparable. Hemodynamic variables were reported as mean and standard deviation. Statistical significance among groups was evaluated using Analysis of Variance and unpaired student t test (two tailed). Inter-group comparisons were made using Bonferroni test. A p-value of <0.05 was considered as statistically significant. In all the three groups the mean heart rate (baseline 84.08 ± 12.50, 87.96 ± 15.73 and 86.92 ± 17.00 respectively) increased during CO2 insufflation and the rise in heart rate continued till exsufflation after which it decreased and at 10 min after exsufflation the heart rates were comparable with the baseline. The inter-group comparison of mean heart rate between I & III was statistically significant at 10, 20, 30 min after CO2 insufflation which continued at exsufflation and 10 min after CO2 exsufflation [p < 0.05]. The inter-group comparison between I & III showed statistically significant difference in systolic blood pressure at 10, 20, 30 min after CO2 insufflation, at exsufflation and 10 min after exsufflation [p = 0.0001] and mean arterial pressure at 5, 10, 20, 30 min after CO2 insufflation, at exsufflation and 10 min after exsufflation [p = 0.0001]. Comparison between Group I and Group III & between Group II and Group III showed highly significant statistical difference in EtCO2 immediately after insufflation and the same trend was seen till the completion of surgery and even 10 min after exsufflation [p = 0.001]. The conclusion drawn from the study was that laparoscopic cholecystectomy induces significant hemodynamic changes intraoperatively, the majority of pathophysiological changes are related to cardiovascular system and are caused by CO2 insufflation .A high intra-abdominal pressure due to CO2 insufflation is associated with more fluctuations in hemodynamic parameters and increased peritoneal absorption of CO2 as compared to low intraabdominal pressure so low pressure pneumoperitoneum is feasible for laparoscopic cholecystectomy and minimizes the adverse hemodynamic effects of CO2 insufflation.

Electronic supplementary material

The online version of this article (doi:10.1007/s12262-012-0484-x) contains supplementary material, which is available to authorized users.     

Treatment outcome of late steroid-resistant nephrotic syndrome: a study by the Midwest Pediatric Nephrology Consortium

Background

Idiopathic nephrotic syndrome (NS) in children is classified as steroid sensitive or steroid resistant. Steroid sensitivity typically portends a low risk of permanent renal failure. However, some initially steroid-sensitive patients later develop steroid resistance. These patients with late steroid resistance (LSR) are often treated with immunosuppressant medications, but the effect of these additional drugs on the long-term prognosis of LSR is still unknown.

Methods

A retrospective chart review was performed on patients diagnosed with idiopathic NS and subsequent LSR during the 8-year study period from 2002 up to and including 2009, with a minimum of 2 years of follow-up. Primary outcome measures were proteinuria and renal function.

Results

A total of 29 patients were classified as having LSRNS. The majority of patients received treatment with calcineurin inhibitors and/or mycophenolate mofetil. Seven patients received three or more non-steroid immunosuppressant medications. Sustained complete or partial remission was achieved in 69 % of patients. Three developed end-stage renal disease, and all others maintained normal renal function. There were 13 episodes of serious adverse events, none of which were fatal or irreversible.

Conclusion

Most patients with LSRNS responded to immunosuppressive therapy by reduction or resolution of proteinuria and preservation of renal function. The results suggest that immunosuppressive treatment is a viable option in NS patients who develop LSR.