Metabolic Profiling Based Quantitative Evaluation of Hepatocellular Metabolism in Presence of Adipocyte Derived Extracellular Matrix

The elucidation of the effect of extracellular matrices on hepatocellular metabolism is critical to understand the mechanism of functional upregulation. We have developed a system using natural extracellular matrices [Adipogel] for enhanced albumin synthesis of rat hepatocyte cultures for a period of 10 days as compared to collagen sandwich cultures. Primary rat hepatocytes isolated from livers of female Lewis rats recover within 4 days of culture from isolation induced injury while function is stabilized at 7 days post-isolation. Thus, the culture period can be classified into three distinct stages viz. recovery stage [day 0–4], pre-stable stage [day 5–7] and the stable stage [day 8–10]. A Metabolic Flux Analysis of primary rat hepatocytes cultured in Adipogel was performed to identify the key metabolic pathways modulated as compared to collagen sandwich cultures. In the recovery stage [day 4], the collagen-soluble Adipogel cultures shows an increase in TriCarboxylic Acid [TCA] cycle fluxes; in the pre-stable stage [day 7], there is an increase in PPP and TCA cycle fluxes while in the stable stage [day 10], there is a significant increase in TCA cycle, urea cycle fluxes and amino acid uptake rates concomitant with increased albumin synthesis rate as compared to collagen sandwich cultures throughout the culture period. Metabolic analysis of the collagen-soluble Adipogel condition reveals significantly higher transamination reaction fluxes, amino acid uptake and albumin synthesis rates for the stable vs. recovery stages of culture. The identification of metabolic pathways modulated for hepatocyte cultures in presence of Adipogel will be a useful step to develop an optimization algorithm to further improve hepatocyte function for Bioartificial Liver Devices. The development of this framework for upregulating hepatocyte function in Bioartificial Liver Devices will facilitate the utilization of an integrated experimental and computational approach for broader applications of Adipogel in tissue e engineering and regenerative medicine

Development of Metabolic Indicators of Burn Injury: Very Low Density Lipoprotein (VLDL) and Acetoacetate Are Highly Correlated to Severity of Burn Injury in Rats

Hypermetabolism is a significant sequela to severe trauma such as burns, as well as critical illnesses such as cancer. It persists in parallel to, or beyond, the original pathology for many months as an often-fatal comorbidity. Currently, diagnosis is based solely on clinical observations of increased energy expenditure, severe muscle wasting and progressive organ dysfunction. In order to identify the minimum number of necessary variables, and to develop a rat model of burn injury-induced hypermetabolism, we utilized data mining approaches to identify the metabolic variables that strongly correlate to the severity of injury. A clustering-based algorithm was introduced into a regression model of the extent of burn injury. As a result, a neural network model which employs VLDL and acetoacetate levels was demonstrated to predict the extent of burn injury with 88% accuracy in the rat model. The physiological importance of the identified variables in the context of hypermetabolism, and necessary steps in extension of this preliminary model to a clinically utilizable index of severity of burn injury are outlined

Management of Duane retraction syndrome: A simplified approach

Duane retraction (or co-contraction) syndrome is a congenital restrictive strabismus which can occur either as an isolated entity or in conjunction with other congenital anomalies and is now listed as a congenital cranial dysinnervation disorder. It is characterized by co-contraction of horizontal recti on attempted adduction causing globe retraction along with variable amounts of upshoots or downshoots. It may have limited abduction or adduction or both and present as esotropic, exotropic, or orthotropic Duane. The diagnosis of this disease is usually clinical. However, recent research has provided a greater insight into the genetic basis of this disease paving a way for a greater role of genetics in the diagnosis and management. This disease can have a varied presentation and hence the treatment plan should be tailor-made for every patient. The indications for surgery are abnormal head posture, deviations in the primary position, retraction and narrowing of palpebral aperture and up- or downshoots during adduction, and sometimes also to improve abduction. The arrival of newer surgical techniques of periosteal fixation (PF) of lateral rectus (LR), partial vertical rectus transposition, or superior or inferior rectus transposition in addition to LR recession with Y-split has vastly improved the management outcomes, providing not only primary position orthophoria but also increased binocular visual fields as well

Non-invasive ventilation for acute exacerbation of COPD with very high PaCO ₂ : A randomized controlled trial

Objective: To assess the role of non-invasive positive pressure ventilation (NIPPV) for management of Indian patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Materials and Methods: Forty patients (mean age 57.6 ± 10.8 years; M:F 31:9) with AECOPD with pH <7.35, admitted to the intensive care unit were included. Patients were randomized to receive NIPPV (N, n = 20) with conventional therapy or conventional therapy (C, n = 20) alone at admission. NIPPV was given through the nasal mask. Incidence of need of endotracheal intubation (ETI) was the primary efficacy variable. Hospital mortality, duration of hospital stay and change in clinical and blood gas parameters were the secondary outcome variables. Results: Mean pH at baseline for N and C groups were similar (7.23 ± 0.07) whereas PaCO 2 was 85.4 ± 14.8 and 81.1 ± 11.6 mm of Hg, respectively. At one hour, patients in N group had greater improvement in pH (P = 0.017) as well as PaCO 2 (P = 0.04) which corroborated with clinical improvement. Whereas need of ETI was reduced in patients who received NIPPV (3/20 vs 12/20, P = 0.003), in-hospital mortality was similar (3/20 and 2/20, P = NS). The mean duration of hospital stay was significantly shorter in N group (9.4 ± 4.3 days) as compared to C group (17.8 ± 2.6 days); P = 0.001. Conclusions: In patients with AECOPD, NIPPV leads to rapid improvement in blood gas parameters and reduces the need for ET