An orally effective dihydropyrimidone (DHPM) analogue induces apoptosis-like cell death in clinical isolates of Leishmania donovani overexpressing pteridine reductase 1

The protozoan parasite Leishmania donovani is the causative agent of visceral leishmaniasis. The enzyme pteridine reductase 1 (PTR1) of L. donovani acts as a metabolic bypass for drugs targeting dihydrofolate reductase (DHFR); therefore, for successful antifolate chemotherapy to be developed against Leishmania, it must target both enzyme activities. Leishmania cells overexpressing PTR1 tagged at the N-terminal with green fluorescent protein were established to screen for proprietary dihydropyrimidone (DHPM) derivatives of DHFR specificity synthesised in our laboratory. A cell-permeable molecule with impressive antileishmanial in vitro and in vivo oral activity was identified. Structure activity relationship based on homology model drawn on our recombinant enzyme established the highly selective inhibition of the enzyme by this analogue. It was seen that the leishmanicidal effect of this analogue is triggered by programmed cell death mediated by the loss of plasma membrane integrity as detected by binding of annexin V and propidium iodide (PI), loss of mitochondrial membrane potential culminating in cell cycle arrest at the sub-G0/G1 phase and oligonucleosomal DNA fragmentation. Hence, this DHPM analogue [(4-fluoro-phenyl)-6-methyl-2-thioxo-1, 2, 3, 4-tetrahydropyrimidine-5-carboxylic acid ethyl ester] is a potent antileishmanial agent that merits further pharmacological investigation.     

Proposed new anthropometric indices of childhood undernutrition

The three conventional anthropometric indicators of childhood undernutrition are stunting (low height-for-age), underweight (low weight-for-age) and wasting (low weight-for-height). Recently a new composite index, namely the Composite Index of Anthropometric Failure (CIAF) has been proposed and utilised to study childhood undernutrition. In this paper, we have attempted to construct three new indices of undernutrition, relative to the CIAF. These three indices are: Stunting Index (SI) = Stunting / CIAF, Underweight Index (UI) = Underweight / CIAF and Wasting Index (WI) = Wasting / CIAF. Furthermore, we have calculated and compared these indices using our dataset as well as other existing datasets. Using our dataset, the sex-combined values of SI, UI and WI were 0.364, 0.866 and 0.684, respectively. The corresponding values among boys were 0.364, 0.866 and 0.729. Among girls, they were 0.380, 0.866 and 0.641, respectively. When applied to the all India dataset, the values of SI, UI and WI were 0.756, 0.788 and 0.266, respectively. Similar values (SI = 0.723, UI = 0.681, WI = 0.294) were observed when they were computed on data available from Coimbatore, South India. In conclusion, we suggest that these three new indices provide additional information on the prevalence of different forms of undernutrition relative to the total level of undernutrition in a particular population.     

Dissipation Study of Thiophanate Methyl Residue in/on Grapes (Vitis vinifera L.) in India

A multi-location field trial was conducted in India during 2006–2008 to evaluate the dissipation pattern of thiophanate methyl (75% WP) in/on grapes at two application rates (500 and 1,000 g a.i. ha^?1). The quantitative analysis of the fungicide residues as carbendazim was performed using a UV/VIS spectrophotometer at the maximum absorption band of 281 nm. The average recovery was found 87% and the relative standard deviations (RSD) were below 3.8%. Following the first order kinetics the fungicide dissipates in grapes with a half-life (t _½) value of 4.74–6.52 days irrespective of locations and doses.     

Younger patients with primary Sjögren’s syndrome are more likely to have salivary IgG anti-muscarinic acetylcholine receptor type 3 antibodies

Acetylcholine type 3 receptor (M3R) is recognized as an autoantigen in primary Sjögren’s syndrome (pSS). Assay of anti-M3R antibody levels in serum is fraught with low sensitivity for diagnosis of pSS. Salivary assay is more likely to improve the diagnostic accuracy. Patients with pSS classified either by the American European Consensus Group (AECG) or American college of Rheumatology (ACR) criteria, attending rheumatology clinic between October 2014 and July 2015 were included. Hospital staff and lupus patients constituted healthy and disease controls, respectively. Evaluation of pSS included clinical evaluation, laboratory tests, ESSDAI and ESSPRI scoring. Unstimulated saliva was collected by the spitting method. Salivary IgG antibody against M3R (anti-M3R) was quantified by indirect ELISA. In this study, 43 patients with pSS, 34 with lupus and 42 healthy controls were recruited. The frequency of anti-M3R antibody levels was 55.81, 17.64 and 7 % for pSS, lupus and healthy controls, respectively. Area under the Receiver Operator Characteristic was 0.7791 (95 % CI,, 0.67–0.87). Sensitivity and specificity of the assay for diagnosis of pSS were 44.19 and 88.16 %, respectively. Salivary anti-M3R IgG antibody positivity was associated with lower age, shorter disease duration and higher globulin levels in our cohort. Salivary anti-M3R IgG antibody assay has high specificity in pSS; younger patients and those with hyperglobulinemia more frequently tested positive for this antibody.     

Evaluation of ELISA and dot blots for the serodiagnosis of neurocysticercosis, in children found to have single or multiple enhancing lesions in computerized tomographic scans of the brain

Although human neurocysticercosis (NCC) is being increasingly recognized in children, diagnosis of the disease can be difficult, and the 'gold standard' criteria that indicate an unambiguous case have still to be established. In the present study, the performances of an ELISA and dot-blot assay, for the detection of antibodies against antigens from larval Taenia solium, were investigated and compared, using sera, from children aged 5-12 years, that were diluted to at least 1:400. Eighty of the subjects (20 aged 5-<8 years and 60 older children) each had the signs and symptoms of NCC, including one brain lesion (N=69) or multiple brain lesions (N=11) that were visible by computed tomography. Another 100 sera, from children who had tubercular meningitis (N=20) or a parasitic disease other than taeniasis/cysticercosis (N=20) or, apart from a minor respiratory-tract infection, appeared healthy (N=60), were also investigated. Most (86%) of the cases of NCC had presented with focal seizures.Analysis of antibody response indicated that the optimum threshold titres for seropositivity were 1:800 for the ELISA and 1:6400 for the dot-blot assays. When used with these thresholds, the ELISA gave a sensitivity, specificity, positive and negative predictive values and diagnostic efficacy of 89%, 81%, 79%, 90%, 85%, respectively. The corresponding values for the dot-blot assay were similar, at 89%, 73%, 72.5%, 89%, 82%, respectively. Both assays were more sensitive, in the detection of the specific antibody response, when used among the paediatric cases of NCC who had multiple brain lesions (100%) than when used among the single-lesion cases (87%). As the ELISA gave higher specificity and diagnostic efficacy than the dot-blot assay, it should be considered the better method for the serological confirmation of NCC in children.     

Case report of two sisters suffering from Weill-Marchesani syndrome with pulmonary stenosis

We report two sisters having a rare congenital anomaly-Weill-Marchesani syndrome having disproportionate short height, restriction of joint movements, brachydactyly, dislocation of lens, bilateral glaucomatous optic atrophy, and pulmonary stenosis.     

Clinico-pathological profile of 12 cases of chorangiosis

Chorangiosis is one of the vascular lesions that involvs terminal chorionic villi. It is commonly associated with various feto-maternal conditions like pre-eclampsia, diabetes etc. However, the clinical significance of this pathological finding has not been studied extensively. The aim of this study was to identify the various conditions associated with chorangiosis and to determine its clinical significance. A retrospective study to identify the cases of placentas diagnosed with chorangiosis was carried out and the clinical and morphological details of these cases were reviewed. Immunostaining for CD34 and muscle-specific actin was also performed to confirm chorangiosis and to exclude chorangiomatosis. A total of 12 cases of chorangiosis were retrieved, most of them were of term gestation. Five of these 12 cases were associated with various maternal conditions including syphilis (2 cases) and single cases of pre-eclampsia, diabetes and jaundice. One case in each had abruptio placenta and non-immune hydrops. Of these 12 cases, seven were stillborn. Microscopically, all 12 cases showed extensive chorangiosis involving terminal villi. In addition, two cases showed focal infarction and one had extensive calcification. Immunostaining for CD34 confirmed increased number of capillaries while muscle-specific actin was negative, excluding chorangiomatosis. The clinico-pathological profile presented in this study suggests that chorangiosis has characteristic pathological features for its recognition and needs to be differentiated from similar conditions like chorangioma and chorangiomatosis. Also, chorangiosis has potential clinical significance and should be mentioned in the pathology report and the patient should be investigated for associated conditions like syphilis, pre-eclampsia, diabetes etc.