CLINICAL STUDY TO EVALUATE AND COMPARE THE EFFICACY OF TWO AYURVEDIC TREATMENT REGIMENS INCLUDING CYATHULA PROSTRATA AND ACHYRANTHES ASPERA IN MANAGING BLEEDING PILES

Background: Sri Lankan Ayurveda physicians mostly recommend Rathkaralheba (Cyathula prostrata) decoction as a treatment for Sraviarshas (bleeding piles) while some patients use Gaskaralheba (Achyranthes aspera) as it is available everywhere. This study was planned to evaluate the effectiveness of two Ayurvedic regimens including Rathkaralheba and Gaskaralheba. Methods: 100 patients with bleeding piles randomly allocated into two groups. Patients of Group A and B were given treatment regimen A and B respectively. Treatment regimen A contained Gaskaralheba decoction, Thriphala tablets and sitz bath. Treatment regimen B included Rathkaralheba decoction, Thriphala tablets and sitz bath. Duration of the treatment was two weeks. Eight clinical parameters relating to bleeding piles were monitored. Results: Data collected from 92 cases (46 cases in each group) were analyzed. The study results showed that statistically highly significant reduction (p<.001) of bleeding, pain and constipation in both groups. Size of the mass has significantly reduced (p<.05) in both groups. In group A, itching was reduced significantly (p<.05) and reduction of prolapse was not significant. In group B, prolapse was reduced significantly (p<.05) but itching was not reduced significantly. Conclusion: Both treatment regimens A and B were found to be equally effective in the treatment of Sraviarshas specially reducing the symptoms of bleeding, pain and constipatio

Development of a distributed international patient data registry for hairy cell leukemia

Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder, comprising only 2% of all leukemias. The Hairy Cell Leukemia Foundation (HCLF) has developed a patient data registry to enable investigators to better study the clinical features, treatment outcomes, and complications of patients with HCL. This system utilizes a centralized registry architecture. Patients are enrolled at HCL Centers of Excellence (COE) or via a web-based portal. All data are de-identified, which reduces regulatory burden and increases opportunities for data access and re-use. To date, 579 patients have been enrolled in the registry. Efforts are underway to engage additional COE’s to expand access to patients across the globe. This international PDR will enable researchers to study outcomes in HCL in ways not previously possible due to the rarity of the disease and will serve as a platform for future prospective research

Epochal changes in the association between malaria epidemics and El Niño in Sri Lanka

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

A Plasma Survey Using 38 PfEMP1 Domains Reveals Frequent Recognition of the Plasmodium falciparum Antigen VAR2CSA among Young Tanzanian Children

PfEMP1 proteins comprise a family of variant antigens that appear on the surface of P. falciparum-infected erythrocytes and bind to multiple host receptors. Using a mammalian expression system and BioPlex technology, we developed an array of 24 protein constructs representing 38 PfEMP1 domains for high throughput analyses of receptor binding as well as total and functional antibody responses. We analyzed the reactivity of 561 plasma samples from 378 young Tanzanian children followed up to maximum 192 weeks of life in a longitudinal birth cohort. Surprisingly, reactivity to the DBL5 domain of VAR2CSA, a pregnancy malaria vaccine candidate, was most common, and the prevalence of reactivity was stable throughout early childhood. Reactivity to all other PfEMP1 constructs increased with age. Antibodies to the DBL2βC2PF11_0521 domain, measured as plasma reactivity or plasma inhibition of ICAM1 binding, predicted reduced risk of hospitalization for severe or moderately severe malaria. These data suggest a role for VAR2CSA in childhood malaria and implicate DBL2βC2PF11_0521 in protective immunity

Investigating the Host Binding Signature on the Plasmodium falciparum PfEMP1 Protein Family

The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family plays a central role in antigenic variation and cytoadhesion of P. falciparum infected erythrocytes. PfEMP1 proteins/var genes are classified into three main subfamilies (UpsA, UpsB, and UpsC) that are hypothesized to have different roles in binding and disease. To investigate whether these subfamilies have diverged in binding specificity and test if binding could be predicted by adhesion domain classification, we generated a panel of 19 parasite lines that primarily expressed a single dominant var transcript and assayed binding against 12 known host receptors. By limited dilution cloning, only UpsB and UpsC var genes were isolated, indicating that UpsA var gene expression is rare under in vitro culture conditions. Consequently, three UpsA variants were obtained by rosette purification and selection with specific monoclonal antibodies to create a more representative panel. Binding assays showed that CD36 was the most common adhesion partner of the parasite panel, followed by ICAM-1 and TSP-1, and that CD36 and ICAM-1 binding variants were highly predicted by adhesion domain sequence classification. Binding to other host receptors, including CSA, VCAM-1, HABP1, CD31/PECAM, E-selectin, Endoglin, CHO receptor “X”, and Fractalkine, was rare or absent. Our findings identify a category of larger PfEMP1 proteins that are under dual selection for ICAM-1 and CD36 binding. They also support that the UpsA group, in contrast to UpsB and UpsC var genes, has diverged from binding to the major microvasculature receptor CD36 and likely uses other mechanisms to sequester in the microvasculature. These results demonstrate that CD36 and ICAM-1 have left strong signatures of selection on the PfEMP1 family that can be detected by adhesion domain sequence classification and have implications for how this family of proteins is specializing to exploit hosts with varying levels of anti-malaria immunity

Current immunological and molecular tools for leptospirosis: Diagnostics, vaccine design, and biomarkers for predicting severity

Leptospirosis is a zoonotic spirochaetal illness that is endemic in many tropical countries. The research base on leptospirosis is not as strong as other tropical infections such as malaria. However, it is a lethal infection that can attack many vital organs in its severe form, leading to multi-organ dysfunction syndrome and death. There are many gaps in knowledge regarding the pathophysiology of leptospirosis and the role of host immunity in causing symptoms. This hinders essential steps in combating disease, such as developing a potential vaccine. Another major problem with leptospirosis is the lack of an easy to perform, accurate diagnostic tests. Many clinicians in resource limited settings resort to clinical judgment in diagnosing leptospirosis. This is unfortunate, as many other diseases such as dengue, hanta virus, rickettsial infections, and even severe bacterial sepsis, can mimic leptospirosis. Another interesting problem is the prediction of disease severity at the onset of the illness. The majority of patients recover from leptospirosis with only a mild febrile illness, while a few others have severe illness with multi-organ failure. Clinical features are poor predictors of potential severity of infection, and therefore the search is on for potential biomarkers that can serve as early warnings for severe disease. This review concentrates on these three important aspects of this neglected tropical disease: diagnostics, developing a vaccine, and potential biomarkers to predict disease severity

Genetics of common variable immunodeficiency: role of transmembrane activator and calcium modulator and cyclophilin ligand interactor

Common variable immunodeficiency (CVID) is the most common clinically manifested primary immunodeficiency, which represents a heterogeneous group of hypogammaglobulinemias of largely unknown molecular defects. The hallmark of the disease is the elevated susceptibility to recurrent infections of respiratory and gastrointestinal tract, mainly due to encapsulated bacteria while a significant proportion of patients with CVID develop autoimmune and lymphoproliferative complications. The primary cause of CVID is still not known. However, a number of distinct genetic defects including in inducible co-stimulator (ICOS), B-cell-activating factor receptor (BAFFR) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) have been identified in a minority of patients with CVID. Mutations in tumour necrosis factor receptor superfamily (TNFRSF) member, TACI, are more frequently found to be associated to the disease in about 10% of patients with CVID, but may require additional immunologic defects for complete expression of the phenotype, as unaffected heterozygotes have also been described. Clinically, patients with TACI mutations could present with the complete spectrum of complications seen in CVID. Recent animal studies have provided substantial information on TACI signalling, yet it still offers an outstanding opportunity for further exploration of the aetiology, as a large part of it remains poorly understood. In this review, we aim at giving an insight into the genetics underlying the CVID and particularly at outlining the role of TACI and its relative contribution to the development of CVID-like phenotypes in human

Antiinflammatory activity of hot water infusion of Nyctanthes arbo-tristis flowers

In Sri Lankan ethnomedicate it is claimed the flowers of Nyctanthes arbo-tristis is effective in the treatment of inflammatory conditions but this has not been scientifically validated. This experiment was carried to investigate the antinflammatory potential of hot water infusion of Nyctanthes arbo-tristis flowers. Oral antiinflammatory activity of hot water infusion of Nyctanthes arbo-tristis flowers (concentrations: 3.75, 7.5, 12.5 and 18.75 mg/kg) was assessed in rats using both acute (carrageenan-induced paw oedema assay) and chronic (formaldehyde induced-paw oedema and cotton pellet-granuloma tests) inflammatory models. In an attempt to investigate its mode of action, antihistamine activity (by wheal test), inhibition of prostaglandin synthesis (by enteropooling test), inhibition of Tumor necrosis factorαsecretion (using human mononuclear cells), and suppression of vascular permeability (acetic acid-induced vascular permeability test) and cytotoxicity (Evans blue test) were assessed. In the carrageenan-induced paw oedema test, hot water infusion simultaneously suppressed both initial and late stages of inflammation in an inversely dose related manner. Hot water infusion also inhibited paw oedema in formalin and cotton pellet granuloma tests. In addition, this infusion exhibited marked anti histamine activity, prostaglandin synthesis inhibition and suppression of vascular permeability. These findings scientifically support the traditional use of Nyctanthes arbo-tristis flowers in treatment of inflammatory conditions

Low serum total nitrite and nitrate levels in severe leptospirosis

Background: The relationship between inducible nitric oxide synthatase activity and disease severity in leptospirosis is unclear. Nitric oxide is converted to nitrites and nitrates, thus nitrite and nitrate levels (NOx) in serum are considered surrogate markers for nitric oxide. NOx are excreted through the kidneys, and elimination is diminished in renal impairment. We assessed the correlation of NOx with disease severity in patients with leptospirosis, compared with healthy controls and non-leptospirosis fever patients.Methods: All patients admitted over a two-month period to the National Hospital, Colombo, Sri Lanka with a clinical picture suggestive of leptospirosis were included. Leptospirosis was confirmed by the microscopic agglutination test (titre≥400). Severe leptospirosis was defined by the presence of two or more of the following criteria: jaundice (bilirubin> 51.3 μmol/l), oliguria (urine output 133 μmol/l or blood urea > 25.5 mmol/l, or the presence of organ dysfunction. Non-leptospirosis fever patients and healthy volunteers were used as control groups. NOx levels were measured using a modified Griess reaction.Results: Forty patients were confirmed as having leptospirosis and 26 of them had severe disease. NOx levels were significantly higher in confirmed leptospirosis patients compared to healthy controls, MAT equivocal patients and non-leptospirosis fever patients (p<0.001). NOx concentrations were also significantly higher in patients with severe compared to mild leptospirosis (p<0.001). Once NOx levels were corrected for renal function, by using the ratio NOx/creatinine, NOx levels were actually significantly lower in patients with severe disease compared to other patients, and values were similar to those of healthy controls.Conclusions: We postulate that high NOx levels may be protective against severe leptospirosis, and that finding low NOx levels (when corrected for renal function) in patients with leptospirosis may predict the development of severe disease and organ dysfunction. © 2013 Kalugalage et al.; licensee BioMed Central Ltd