A PHARMACOGNOSTIC AND PHARMACOLOGICAL REVIEW ON ALSTONIA SCHOLARIS

Alstonia scholaris, commonly known as devil's tree, is an important medicinal plant in the various folk and traditional systems of medicine in Asia, Australia, and Africa. The plant is used in Ayurvedic, Unani, and Siddha types of alternative medicinal systems. The decoction, mostly prepared from the bark, is used to treat a variety of diseases, of which the most important is malaria. In Ayurveda, it is used as a bitter and as an astringent herb for treating skin disorders, malarial fever, urticaria, chronic dysentery, diarrhea, and in snake bite. A. scholaris is also observed to possess antioxidant, immunomodulatory effects, and free radical scavenging, anti-inflammatory, antimutagenic, anticancer, analgesic, hepatoprotective, wound healing, antidiarrheal, and antiplasmodial activities. The current review summarizes the numerous ethnobotanical and traditional uses as well as the phytochemical and pharmacological report on A. scholaris

Sputum versus bronchial washings for diagnosis of pulmonary tuberculosis- a prospective study of 53 patients

Background: Tuberculosis is a major global public health problem. It is caused by mycobacterium tuberculosis and it is a leading cause of death in developing countries like India. WHO recommends the detection of acid fast bacilli in sputum as the initial diagnosis of pulmonary TB. Tuberculosis is spread from person to person through air by droplet nuclei. So, early detection and prompt treatment of tuberculosis is main cornerstone to prevent transmission into community. Bronchial washing is very helpful for early detection of mycobacterium tuberculosis.Methods: This is a prospective study of 53 sputum smear negative patients underwent for bronchoscopy. After a detailed medical history and physical examination, Patients with a negative sputum smear AFB examination and a strong clinco-radiological suspicion of pulmonary tuberculosis were then counseled, consented and subjected to fiber-optic bronchoscopy with bronchial washings and bronchial biopsy in case of endobronchial lesions.Results: Our study showed mean age of patient is about 43.49 year and has predominantly male patients. Most cardinal symptoms were fever (83%) and cough (74%). Most radiological findings were consolidation and cavity lesion accordingly. Sputum culture was positive in 14 (26%) patients out of 53 patients and bronchial washing smear positive for AFB in 30 (57%) patients and bronchial washing culture positive for AFB in 40 (75%) patients out of 53 patients.Conclusions: Bronchial washings analysis for detection of AFB is much more reliable in comparison to direct smear microscopy and direct sputum culture examination

A study of the clinical profile of 50 patients of COPD with correlation between clinical, radiological and spirometric evaluation

Background: Chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable disease that is characterised by persistent respiratory symptoms and airflow limitation that is due to airway and/ or alveolar abnormalities usually caused by significant exposure to noxious particles or gases. Tobacco smoking, occupational exposure to organic and inorganic dusts, chemical agents and fumes and biomass cooking are the risk factors for COPD. Chronic dyspnoea, cough, sputum production, wheezing and chest tightness are the common symptoms of COPD. The present study was undertaken to evaluate the clinical, radiological and spirometric parameters in patients with COPD and to demonstrate a correlation between them.Methods: This was a prospective study of 50 patients of COPD who presented to out- patient department. We included all patients above 40 years of age with a smoking index of 200 or more, or history of exposure to occupational dust, biomass fuel gas or exposure to other obnoxious gases; and who had history of dyspnoea and cough. Spirometry was performed to confirm the diagnosis and to grade the severity of airflow obstruction. History of dyspnoea, cough, sputum production, wheezing, chest tightness, fever, weight loss and the number of exacerbations in the previous year was noted. We then performed a detailed clinical examination. Blood was sent for haemogram and arterial blood gas analysis and all patients underwent an ECG, 2- D Echo and HRCT of the thorax. We then studied the correlation between the clinical, radiological and spirometric profiles in these patients.Results: Out of the 50 patients, majority was between 50-59 years of age, with male to female ratio of 1.94:1.00. History of smoking was present in 74% patients, exposure to biomass fuel in 12% and exposure to occupational dust in 6% patients. Commonest symptom was dyspnoea (in 100% patients) followed by cough (88%), sputum production (68%), wheezing (58%), chest tightness and fever (30%) and weight loss (28%). HRCT was positive in 75% patients, while ECG changes were seen in 42% patients and pulmonary hypertension was present in 54% patients. A significant association was observed between grade 5 dyspnoea on mMRC, hypoxia, hypercarbia, pulmonary hypertension and Gold-5 airflow obstruction.Conclusions: In the present study of 50 cases, COPD was seen predominantly in male patients, with a mean age of presentation between 50- 59 years. Tobacco smoking was the commonest etiological factor. Clinical symptoms most commonly documented were dyspnoea, cough with or without expectoration, wheezing, chest tightness, fever and weight loss. A significant association was observed between grade 5 dyspnoea on mMRC, hypoxia, hypercarbia, pulmonary hypertension and Gold-5 airflow obstruction

Abundant and equipotent founder cells establish and maintain acute lymphoblastic leukaemia

High frequencies of blasts in primary acute lymphoblastic leukaemia (ALL) samples have the potential to induce leukaemia and to engraft mice. However, it is unclear how individual ALL cells each contribute to drive leukaemic development in a bulk transplant and the extent to which these blasts vary functionally. We used cellular barcoding as a fate mapping tool to track primograft ALL blasts in vivo. Our results show that high numbers of ALL founder cells contribute at similar frequencies to leukaemic propagation over serial transplants, without any clear evidence of clonal succession. These founder cells also exhibit equal capacity to home and engraft to different organs, although stochastic processes may alter the composition in restrictive niches. Our findings enhance the stochastic stem cell model of ALL by demonstrating equal functional abilities of singular ALL blasts and show that successful treatment strategies must eradicate the entire leukaemic cell population

Evaluation of anti-asthmatic and anti-cholinergic activity of ethanolic extract of Tectina grandis Linn. bark

Background: Asthma is a chronic disease that affects approximately 300 million people worldwide. Tectona grandis Linn. bark, also known as Teak (English), is traditionally used to treat asthma. However, the scientific data on anti-asthmatic and anti-cholinergic of this plant has got little attention. An attempt has been based on ethanolic extract of bark of Tectona grandis Linn. shown a tremendous effect on asthma when comparative study was done with normal and treated group.Methods: The anti-asthmatic activity of a 95% ethanol and 5% distilled water extract of dried and fresh Tectona grandis Linn. bark, was evaluated against histamine and acetylcholine-induced preconvulsive dyspnea (PCD) in guinea pigs fasted for 24 h were exposed to an atomized fine mist of 2% histamine dihydrochloride and acetylcholine aerosol (dissolved in normal saline) using nebulizer at a pressure of 300 mmHg in the histamine chamber (24×14×24 cm, made of perplex glass. They were divided in groups Mepyramin (8 mg/kg) intraperitonially, atropine aerosol and Tectona grandis bark formulation (2.5, 5, 10 gm/kg) were administered orally 30 min prior to exposure. Animals, which did not develop typical asthma within 6 minutes, were taken as protected.Results: Ethanolic extract of Tectona grandis Linn. bark at 5 and 10 gm/kg significantly reduce bronchoconstriction as compared to control group along with significant mast cell stabilization activity.Conclusions: In conclusion, the present study shows that the ethanolic bark extract of Tectona grandis Linn. has potential antiasthamatic and antichlolinergic action in histamine and acetylcholine broncocontraction in guinea pigs

Probing Plasmodium falciparum sexual commitment at the single-cell level

Background: Malaria parasites go through major transitions during their complex life cycle, yet the underlying differentiation pathways remain obscure. Here we apply single cell transcriptomics to unravel the program inducing sexual differentiation in Plasmodium falciparum. Parasites have to make this essential life-cycle decision in preparation for human-to-mosquito transmission. Methods: By combining transcriptional profiling with quantitative imaging and genetics, we defined a transcriptional signature in sexually committed cells. Results: We found this transcriptional signature to be distinct from general changes in parasite metabolism that can be observed in response to commitment-inducing conditions. Conclusions: This proof-of-concept study provides a template to capture transcriptional diversity in parasite populations containing complex mixtures of different life-cycle stages and developmental programs, with important implications for our understanding of parasite biology and the ongoing malaria elimination campaign

Designer lipid-like peptides

A crucial bottleneck in membrane protein studies, particularly G-protein coupled receptors, is the notorious difficulty of finding an optimal detergent that can solubilize them and maintain their stability and function. Here we report rapid production of 12 unique mammalian olfactory receptors using short designer lipid-like peptides as detergents. The peptides were able to solubilize and stabilize each receptor. Circular dichroism showed that the purified olfactory receptors had alpha-helical secondary structures. Microscale thermophoresis suggested that the receptors were functional and bound their odorants. Blot intensity measurements indicated that milligram quantities of each olfactory receptor could be produced with at least one peptide detergent. The peptide detergents' capability was comparable to that of the detergent Brij-35. The ability of 10 peptide detergents to functionally solubilize 12 olfactory receptors demonstrates their usefulness as a new class of detergents for olfactory receptors, and possibly other G-protein coupled receptors and membrane proteins

Posterior Approach To Kidney Dissection: An Old Surgical Approach For Integrated Medical Curricula

Integrated medical curricular changes are altering the historical regional anatomy approach to abdominal dissection. The renal system is linked physiologically and biochemically to the cardiovascular and respiratory systems, yet anatomist often approach the urinary system as part of the abdomen and pelvic regions. As part of an integrated curriculum, the renal system must be covered relatively quickly after the thorax in the cadaver lab, often without the opportunity to fully appreciate the rest of the abdominal contents. This paper provides dissection instructions that follow the one of the historical surgical approaches for nephrectomy, including preservation of the posterior abdominal wall neurovasclature. Dissection procedures were developed for first year medical students, intending this posterior approach to the kidneys to be their first introduction to the renal system. It has been successfully implemented with first year medical students at the University of New England, College of Osteopathic Medicine. Utilizing this posterior approach to the kidney enabled the study of the anatomy of the kidneys, suprarenal glands and renal vessels, as well as the muscles of the lumbar spine, while maintaining the integrity of the anterior abdominal wall and peritoneal cavity for future gastrointestinal and reproductive system-based dissections

Network based transcription factor analysis of regenerating axolotl limbs

<p>Abstract</p> <p>Background</p> <p>Studies on amphibian limb regeneration began in the early 1700's but we still do not completely understand the cellular and molecular events of this unique process. Understanding a complex biological process such as limb regeneration is more complicated than the knowledge of the individual genes or proteins involved. Here we followed a systems biology approach in an effort to construct the networks and pathways of protein interactions involved in formation of the accumulation blastema in regenerating axolotl limbs.</p> <p>Results</p> <p>We used the human orthologs of proteins previously identified by our research team as bait to identify the transcription factor (TF) pathways and networks that regulate blastema formation in amputated axolotl limbs. The five most connected factors, c-Myc, SP1, HNF4A, ESR1 and p53 regulate ~50% of the proteins in our data. Among these, c-Myc and SP1 regulate 36.2% of the proteins. c-Myc was the most highly connected TF (71 targets). Network analysis showed that TGF-β1 and fibronectin (FN) lead to the activation of these TFs. We found that other TFs known to be involved in epigenetic reprogramming, such as Klf4, Oct4, and Lin28 are also connected to c-Myc and SP1.</p> <p>Conclusions</p> <p>Our study provides a systems biology approach to how different molecular entities inter-connect with each other during the formation of an accumulation blastema in regenerating axolotl limbs. This approach provides an in silico methodology to identify proteins that are not detected by experimental methods such as proteomics but are potentially important to blastema formation. We found that the TFs, c-Myc and SP1 and their target genes could potentially play a central role in limb regeneration. Systems biology has the potential to map out numerous other pathways that are crucial to blastema formation in regeneration-competent limbs, to compare these to the pathways that characterize regeneration-deficient limbs and finally, to identify stem cell markers in regeneration.</p