Hepatoprotective Effects of Aureobasidium pullulans Derived ß 1,3-1,6 Glucans in a Murine Model of Non-alcoholic Steatohepatitis.

Background: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are highly prevalent conditions characterized by inflammation and fibrosis of the liver, which can progress to cirrhosis and hepatocellular carcinoma if left untreated. Conventional modalities are mainly symptomatic, with no definite solution. Beta-glucan-based biological response modifiers are a potential strategy in lieu of their beneficial metabolic effects. Aureobasidium pullulans strains AFO-202 and N-163 beta-glucans were evaluated for anti-fibrotic and anti-inflammatory hepatoprotective potentials in a NASH animal model in this study. Methods: In the STAM™ murine model of NASH, five groups were studied for 8 weeks: (1) vehicle (RO water), (2) AFO-202 beta-glucan; (3) N-163 beta-glucan, (4) AFO-202+N-163 beta-glucan, and (5) telmisartan (standard pharmacological intervention). Evaluation of biochemical parameters in plasma and hepatic histology including Sirius red staining and F4/80 immunostaining were performed. Results: AFO-202 beta-glucan significantly decreased inflammation-associated hepatic cell ballooning and steatosis. N-163 beta-glucan decreased fibrosis and inflammation significantly (P value < 0.05). The combination of AFO-202 with N-163 significantly decreased the NAFLD Activity Score (NAS) compared with other groups. Conclusion: This preclinical study supports the potential of N-163 and AFO-202 beta-glucans alone or in combination as potential preventive and therapeutic agent(s), for NASH.

Potential of Combination of Bone Marrow Nucleated and Mesenchymal Stem Cells in Complete Spinal Cord Injury.

BACKGROUND: Cell-based therapies represent one of the definitive treatment approaches to SCI which, to become a routine clinical application, is marred by several known unknowns. The Bone Marrow Mononuclear Cells (BMMNCs) and Mesenchymal Stem Cells (MSCs) represent the most clinically applied cell types for SCI in humans, with safety established, and to an extent, efficacy reported. METHODS: In this review, we have analysed the clinical studies performed using BMMNC and MSC for complete SCI separately, and the potential for applying those cells in combination. We have also analysed those factors whose outcome in animal studies of SCI could be evaluated in depth but the clinical outcome cannot be evaluated intrinsically owing to practical difficulties. CONCLUSION: A combination of these two cell types, BMMNC and MSC, has been proven to be advantageous than applying them separately. Therefore, a thorough evaluation including the rationale and potential implications of applying these two therapies has been presented here, and we hypothesize that such a combination is likely to improvise the outcome of a wholesome approach to spinal cord regeneration after SCI.

The GVK EMRI maternal and neonatal transport system in India: a mega plan for a mammoth problem.

Maternal and infant mortality has been a major concern in India with the Government taking serious efforts to achieve the Millennium Development Goals by 2015. Ganapathy Venkata Krishna Reddy Emergency Management and Research Institute (GVK EMRI) is one such effort and is the country's first emergency service provider working under the public-private partnership model to provide emergency response services and quality pre-hospital care to any sick person, pregnant mothers, and sick neonates. Since the introduction of the emergency medical services, institutional deliveries have increased in all states and union territories where the ambulances have been deployed and the majority of mothers have been provided the required emergency care at the appropriate time. This in turn has helped in considerably reducing the maternal mortality. GVK EMRI has partnered with the government of Tamil Nadu and deployed specialized neonatal ambulances to ensure safe transport of newborns. The safe transport of sick, vulnerable neonates and the improvement in survival of transported neonates over the years advocate scaling up of this program to other states, which would greatly contribute towards reducing infant and neonatal mortality.

Spontaneous CSF Rhinorrhea Our Experience.

To analyse the possible factors contributing to spontaneous cerebrospinal fluid (CSF) rhinorrhea and to assess the outcome of Transnasal endoscopic repair at our centre. Retrospective case series of patients with spontaneous CSF rhinorrhea at our institution from Jan 2006 to May 2010. 7 patients were diagnosed with spontaneous CSF rhinorrhea. 5 of the 7 patients were obese, middle aged females managed with Transnasal endoscopic repair with fascia lata auto graft. Successful repair of CSF rhinorrhea was achieved in all the patients with a single endoscopic procedure; no patient required a revision procedure. Spontaneous CSF rhinorrhea is a rare condition seen mostly in middle aged obese females with the anterior part of the cribriform plate being the most common site of leak. HRCT paranasal sinus (1 mm cuts) was an effective modality of investigation in our study with ancillary investigations been CT Cisternography, CSF analysis and MRI for inactive leaks. In the absence of a large breech of the skull base, endoscopic repair of CSF rhinorrhea carries a high success rate with a high safety margin and very low morbidity rate.

Ingestion dose from 238U, 232Th, 226Ra, 40K and 137Cs in cereals, pulses and drinking water to adult population in a high background radiation area, Odisha, India.

A natural high background radiation area is located in Chhatrapur, Odisha in the eastern part of India. The inhabitants of this area are exposed to external radiation levels higher than the global average background values, due to the presence of uranium, thorium and its decay products in the monazite sands bearing placer deposits in its beaches. The concentrations of (232)Th, (238)U, (226)Ra, (40)K and (137)Cs were determined in cereals (rice and wheat), pulses and drinking water consumed by the population residing around this region and the corresponding annual ingestion dose was calculated. The annual ingestion doses from cereals, pulses and drinking water varied in the range of 109.4-936.8, 10.2-307.5 and 0.5-2.8 µSv y(-1), respectively. The estimated total annual average effective dose due to the ingestion of these radionuclides in cereals, pulses and drinking water was 530 µSv y(-1). The ingestion dose from cereals was the highest mainly due to a high consumption rate. The highest contribution of dose was found to be from (226)Ra for cereals and drinking water and (40)K was the major dose contributor from the intake of pulses. The contribution of man-made radionuclide (137)Cs to the total dose was found to be minimum. (226)Ra was found to be the largest contributor to ingestion dose from all sources.

Spatial distribution of fallout 137Cs in the coastal marine environment of India.

The data on the fallout (137)Cs in the coastal marine environment assume significance in view of massive expansion of nuclear power plants in the Asia-Pacific region and to fulfill the benchmark study required to evaluate the possible impact of the Fukushima radioactive releases in the Asia-Pacific region. Measurements of (137)Cs in sea water, along with salinity and temperature, were carried out at 30 locations covering the coastal area of the Arabian Sea and the Bay of Bengal. For the present study the Indian coastal area is divided in three different regions. The (137)Cs concentration in sea water of the entire Indian coastal region varies from 0.30 to 1.25 Bq m(-3). The data obtained in the present study was compared with the North Indian Ocean data and it was observed that there is a 33% decrease in the Arabian Sea (region I), 50% in the high rainfall coastal area (region II) and 24% in the Bay of Bengal (region III).

Differences in thermal adaptation of infants delivered at primary or tertiary care facilities in India.

OBJECTIVE: To compare the pattern of thermal stabilization seen in infants born at a rural primary health center (PHC) with that of infants born in an modern urban tertiary care hospital (TCH). STUDY DESIGN: Abdominal temperature (Ta) and foot temperature (Tf) of healthy term newborn infants were monitored and electronically recorded continuously from birth in the delivery room (DR) until 12 h of life in the postnatal ward (PNW) at two sites. A total of 71 infants were enrolled in the study: 51 infants at the PHC and 20 infants at the TCH. RESULT: In infants delivered at TCH the maximum mean (±s.d.) Ta of 36.4 ° C ± 0.48 was reached by 12 h, while at PHC maximum mean Ta was 35.4 °C (1.98) by 10.5 h. The mean Tf improved from the lowest value of 29.7 °C ± 1.3 at 4.5 h to 32.9 °C±1.6 by 12 h of life in infants delivered at TCH, whereas in infants delivered at PHC Tf remained low (maximum 30.7 °C) all through 12 h. The mean Td (Ta-Tf) gradually decreased from a maximum of 5.9 °C ± 1.6 at 4.5 h to 3.5 °C ± 1.5 by 12 h of life in infants born at TCH, but the Td remained at >5 °C even after 6 h of life in infants born at PHC, which was statistically significant (P<0.05). The calculated area between the Ta and Tf, a proxy for metabolic stress was greater in babies born at PHC than those born at TCH. CONCLUSION: Our study shows that although both groups of newborn infants experienced significant thermal stress, infants delivered at PHC experienced significantly greater thermal stress than babies born at TCH. This difference could be attributed to the differences in thermal environment of DR and PNW between PHC and TCH.

Studies of meconium-induced lung injury: inflammatory cytokine expression and apoptosis.

To review current literature related to cellular mechanisms of meconium-induced lung injury (MILI). Review of published experimental in vitro and in vivo MAS studies using human and animal lung cells. We found that meconium induces expression of cytokines and angiotensin II (ANG II)-induced apoptotic process in the lung cells. We postulate that inflammatory cytokines induce ANG II expression, which causes apoptotic cell death after binding to its AT1 receptors. We also demonstrated expression of serpins associated with meconium instillation into the lungs. Serpins are proteins that inhibit cellular proteases and elastases. Expression of serpins may be an attempt to recover lung from these injurious effects. In summary our studies show that whereas meconium induces inflammatory cytokines and subsequent cell apoptosis, the lung cells also try to protect themselves by inducing serpins. The balance of these interactions will determine the residual damage. We believe these new findings are very important in understanding of MILI.

Meconium-induced release of nitric oxide in rabbit alveolar cells.

Previous studies have shown meconium-induced lung injury occurs throughout release of inflammatory cytokines. The exact mechanism of cytokine-induced apoptosis is not known. In this study we hypothesized that meconium-induced apoptosis in the lungs is mediated through the production of inducible nitric oxide (NO). We studied two groups of newborn rabbit pups: one group was instilled with meconium and other with normal saline. We measured precursors of NO in lung lavage from both groups of rabbits and NO levels were calculated accordingly. The levels of NO and NO-derivatives increased significantly in both groups. However NO expression in meconium group 2 h after meconium instillation was significantly higher than in saline-instilled group suggesting NO production plays a role in meconium-induced inflammation.

Treatment of MAS with PPHN using combined therapy: SLL, bolus surfactant and iNO.

The objective of the study was to compare the effectiveness of surfactant treatment either by bolus or surfactant lung lavage followed by inhaled nitric oxide (iNO) therapy in infants with meconium aspiration syndrome (MAS) complicated by persistent pulmonary hypertension (PPHN). In this study, thirteen infants with diagnosis of MAS and PPHN were first treated with conventional respiratory support. Then between 2 and 22h of life they were randomized either to bolus surfactant treatment (n=6) or surfactant lung lavage (SLL, n=7) treatment. Then all infants were treated with iNO therapy. The groups were compared with regard to their clinical course: changes in PaO(2), FiO(2), MAP, OI, A-a oxygen gradient, duration of iNO therapy, length of ventilation and hospitalization. Complications and mortality were also compared. The results showed that infants treated with SLL had significant improvements in oxygenation, decreases in MAP and A-a gradients. But there were no significant differences in duration of ventilation, iNO treatment, length of hospitalization or complications. In conclusion these data show no advantage of SLL therapy over bolus surfactant treatment in infants with MAS complicated by PPHN.

Global notes: mysteries of 'the first' and the 'last breath' and the gift of Neonatal Resuscitation Program.

First and last breaths define the life span of a living animal including humans. Humans have been fascinated more with the last breath-the death. Neonatologists are focused on initiating the first breath. Millions of babies around the world do not have a chance of survival beyond a few moments after birth for lack of successful initiation of their first breath. Both neonatologists and other health care providers work hard to separate the last breath from the first breath using resuscitative measures thanks to the NRP developed and propagated two decades ago. This paper is dedicated to the initiators of the program, and all those dedicated health care teams working around the globe to save newborn lives.

Global notes: instinctive resuscitation of a newborn by mother: a lesson to be learned.

The fact is that mother is the best combined pediatrician and neonatologist in the world. She is the most passionate and vested caregiver for the newborn, whether living and delivering in a modern hospital in a developed country or in a village in the remotest part of the globe; whether she is literate or illiterate. Let us focus our efforts on providing mothers the additional skills in caring for the baby in difficult situations immediately after birth.

Global minute: water and health--walking for water and water wars.

Water is a precious commodity and needs to be conserved. Water plays an important role in daily life: in sustenance of life, sanitation and food production. Scarcity of water may lead to water wars among water-stressed nations. Therefore, there is a need for development of democratic principles among nations to assure free access to water to one and all. In view of the fact that lack of access to clean water affects health and infant mortality gap. Great importance is given to improve water resources in the communities (Millennium Development Goal number 7). As professionals entrusted with the health of mother and child, we must strive to improve access to potable clean water to communities in underdeveloped countries.

Global notes: the tale of two giants--China and India.

The two giant nations India and China are the emerging powers of the 21st century. There is a debate as to which of the two will edge ahead. This article compares the gains made by the two nations in economics, technology and human development.

Global notes: counting the world's poor--how do we define poverty?

Health professionals are in constant interaction with parents and infants who are victims of poverty and poor socioeconomic status. But an important question remains: do we know how to define poverty? Defining poverty accurately is important as the definition is the basis of policy development. The definition of poverty has changed during the last quarter century. In addition to economic considerations, it is broadened to include other dimensions of life such as literacy, health and longevity. This article attempts to provide national and international definitions of poverty, the magnitude and effects of poverty.