Acute and sub-acute toxicity study of anti-obesity herbal granules in Sprague Dawley rats.

Toxicological studies are essential for developing novel medications in pharmaceutical industries including ayurvedic preparation. Hence, the present study is aimed to evaluate acute and 28-days repeated dose oral toxicity of anti-obesity polyherbal granules (PHG) in Sprague Dawley rats by OECD guidelines No 425 and 407, respectively. In an acute oral toxicity study, a single dose of 2 g/kg PHG was administered to rats and mortality, body weight, and clinical observations were noted for fourteen days. However, in the subacute oral toxicity study, the PHG was administered orally at doses of 0.3, 0.5 and 1 g/kg daily for 28 days to rats. Food intake and body weight were recorded weekly. On the 29th day, rats were sacrificed and subjected to haematological, biochemical, urine, necropsy, and histopathological analysis. In an acute oral toxicity study, no treatment-related, mortality, behavioral changes, and toxicity were found throughout fourteen days. Likewise, in the sub-acute toxicity study, no mortality and toxic effects were found in haematology, biochemical, urine, necropsy and histopathological analysis in rats for 28 days of treatment with PHG. Based on these results, the LD50 of PHG was found to be greater than 2 g/kg and the no-observed-adverse-effect level (NOAEL) of PHG for rats was found to be 0.5 g/kg/day. Thus, anti-obesity polyherbal granules showed a good safety profile in animal studies and can be considered an important agent for the clinical management of obesity.

Haemorrhagic transformation following ischaemic stroke: A retrospective study.

The aim of this study was to identify the prevalence of haemorrhagic transformation (HT) in patients with ischaemic stroke, and evaluate its association with medical comorbidities, stroke subtypes, premorbid medication, and long-term survival. To achieve this, we performed a retrospective analysis of 527 consecutive stroke rehabilitation patients. Of these, 102 (19.4%) developed HT. Older patients, and those with large artery strokes, had a higher risk of HT. Forty-one patients received alteplase (rtPA), of which 15 (36.6%) developed HT. A total of 129 (24.5%) patients were taking aspirin prior to their stroke and, of these, 39 (30.2%) developed HT. Twenty-three (4.36%) patients were taking vitamin k antagonists, prior to stroke, of which 14 (60.9%) developed HT. There were 102 patients (19.35%) with underlying atrial fibrillation, of whom 55 (53.9%) developed HT. Patients with known ischaemic heart disease had an increased risk of HT, and patients with HT had significantly lower total cholesterol levels (4.96 vs. 5.34) and lower LDL cholesterol levels (3.20 vs. 3.5). In conclusion, older age, atrial fibrillation, treatment with oral anticoagulants and antiplatelet medications prior to stroke, low total and LDL cholesterol, and rtPA use, are all associated with HT. Survival was not affected by the presence of HT.

Primary Ewing sarcoma of the coronoid process of mandible.

Ewing sarcoma (ES) is a rare, primary malignancy of the bone that occurs mainly in childhood and early adolescence. ES usually occurs in long bones of the axial skeleton. Although uncommon in the jaws, ES at this site is most likely to occur in the posterior mandible. The outcome for patients with localised disease has improved over the decades, due to better combination chemotherapies and better methods of local control. We present the clinicopathologic features and management of a case of ES that developed in the left coronoid process of the mandible of a 31-year-old male. Chemotherapy and, later, a segmental mandibulectomy were used to achieve local control. A fibula-free flap repair was performed with good aesthetic results. This case elucidates the importance of the interdisciplinary approach required for the evaluation and treatment of this aggressive neoplasm.

Spinal metastasis of breast cancer presenting after 25 years: An extremely rare presentation.

Breast cancer is the most frequently diagnosed cancer in females of the developed world and is gradually becoming the leading cause in the developing world as well. The innate biology of breast cancer is marked by varied presentations, characteristics, response, recurrence and metastatic phenomenon. Even an early stage breast cancer has the potential to recur and/or metastasize after extremely long duration and this possibility should be borne in the clinician's mind.

Influence of protein tyrosine phosphatase gene (PTPN22) polymorphisms on rheumatic heart disease susceptibility in North Indian population.

This study was aimed to assess the association of Protein tyrosine phosphatase non-receptor22 (PTPN22) gene single nucleotide polymorphisms (SNPs) with rheumatic heart disease (RHD) susceptibility in 400 RHD patients and 300 controls. The PTPN22 polymorphisms (rs2476601, rs1217406 and rs3789609) were genotyped using Taqman probes (Applied Biosystems, Foster City, CA). Statistical analysis was performed by spss and haplotype analysis by snpstat. The frequencies of variant alleles were not different between controls and cases (rs2476601: 2.00% & 1.05%; rs1217406: 36.33% & 34.75%; and rs3789609: 38.17% & 40.00%, respectively]. However, G rs2476601 A rs1217406 T rs3789609 haplotype turned out to be a low risk factor for RHD (P = 0.0042) predisposition in females and adult patients. This study suggests PTPN22 haplotype may modulate the risk to RHD in North Indians.

Association of a distinct strain of hollyhock yellow vein mosaic virus and Ludwigia leaf distortion betasatellite with yellow vein mosaic disease of hollyhock (Alcea rosea) in India.

A distinct strain of hollyhock yellow vein mosaic virus (HoYVMV) and Ludwigia leaf distortion betasatellite (LuLDB) were associated with yellow vein mosaic of hollyhock. The viral DNA genome (JQ911766) and betasatellite (JQ408216) shared highest nucleotide sequence identity (89.2 %) with HoYVMV (the only available sequence in GenBank) and 92 % identity with LuLDB. Agroinfiltration of HoYVMV and LuLDB induced yellow vein mosaic symptoms on hollyhock, thereby demonstrating causality of the disease.

First Report of Fusarium acuminatum on Pigeonpea in India.

Pigeonpea (Cajanus cajan (L.) Millsp.) is the most important protein rich grain legume crop being cultivated worldwide. During surveys (2010 through 2012) conducted in major pigeonpea growing states in southern and central India (Andhra Pradesh, Karnataka, and Maharashtra), rapid mortality of pigeonpea plants was observed. This occurred in all of the surveyed areas with disease incidence of 20 to 60% irrespective of cultivar and crop growth stage. Symptoms included chlorosis, drooping and rolling of the leaves followed by rapid mortality of whole plant. Pinkish growth on infected stems and branches was observed and the inner layer of the infected stem had brown discoloration. Xylem vessels of the infected plants were healthy and did not show any blackening. Isolations from infected stem tissues consistently yielded cultures of Fusarium sp. on potato dextrose agar (PDA) medium. Monoconidial isolation from three separate isolates was used to establish pure cultures. The morphological characters of the fungus were consistent with descriptions in Fusarium keys (1) for Fusarium acuminatum (Ellis & Everhart). The mean colony growth was 86 mm after 7 days, with white aerial mycelium developing brownish pigmentation in the center on PDA. The dorsal side of the colony had rose to burgundy pigmentation. Macroconidia were broadly falcate with 3 to 5 septa, and were 3 to 8 × 39 to 64 µm. Microconidia were absent and chlamydospores formed in chains of 20 to 50 µm. Koch's postulates were established on seedlings of pigeonpea (cv. ICP 7119) using root dip inoculation of 10-day-old seedlings. The roots were immersed in a conidial suspension (6 × 106 conidia/ml) for 2 to 3 min; the control plants' roots were immersed in sterilized distilled water in a beaker. Inoculated seedlings were transplanted into pre-irrigated pots (12 cm) containing sterilized vertisol and sand (3:1). Five seedlings were used for each of three replications. Inoculated plants were kept in the greenhouse at 28 ± 2°C and irrigated with sterilized water. Inoculated plants developed symptoms identical to those observed in the field and disease incidence reached 100% within 96 h after inoculation. The experiment was conducted twice with two independent sets of plants. No symptoms were observed in water-inoculated control plants. The rDNA internal transcribed spacer (ITS sequence) was amplified with ITS1 and ITS4 primers (4). The amplicons of both forward and reverse (438 bp) were sequenced and submitted to GenBank (Accession No. JX177431). A BLASTn search revealed 100% sequence similarity to the nucleotide sequence of F. acuminatum (Ellis & Everhart) (GenBank Accession No. HQ443205). To our knowledge, this is the first report with confirmed molecular identification of F. acuminatum on pigeonpea. Occurrence of F. acuminatum on various plant species have been reported by Summerell et al. (3). Presence of F. acuminatum from soils of pigeonpea fields have been reported; however, no information on location, symptoms, plant mortality, and identification of pathogen has been provided (2). References: (1) J. F. Leslie and B. A. Summerell. Pages 122-123 in: The Fusarium Laboratory Manual. Blackwell Publishing Professional, Hoboken, NJ, 2006. (2) A. P. Singh and S. N. Bhargava. Phytopathol. Z. 100:300, 1981. (3) B. A. Summerell et al. Fungal Diversity 46:1, 2011. (4) T. J. White et al. Pages 315-322 in: PCR protocols: Guide to Methods and Applications, San Diego, Academic Press, 1990.

Hydrogeochemistry of boron in borewell water of Durgapur coal mine area, District Chandrapur, Maharashtra, India.

Two formations, Barakar and Talchir belonging to Lower Gondwana sequence form aquifer in Durgapur area. Groundwater of these formations sampled for boron investigation in two seasons, Post-monsoon and Pre-monsoon. The water quality differed from aquifer to aquifer, mainly with respect to conductivity and B contents. Talchir groundwater shows greater conductivity and greater B content than Barakar groundwater. The maximum concentration of B was found in Talchir pre-monsoon groundwater. Greater B in Talchir groundwater is attributed to glacio-marine environment of sediment deposition. The correlation of B with major ions also varies. It shows positive correlation with conductivity, Na, HCO3 and SO4 in Barakar groundwater and with SO4 in Talchir groundwater. Seasonal variation in concentration of B exists but not appreciable.

Antihypercholesterolaemic influence of dietary tender cluster beans (Cyamopsis tetragonoloba) in cholesterol fed rats.

BACKGROUND & OBJECTIVES: Cluster beans (Cyamopsis tetragonoloba) are rich source of soluble fibre content and are known for their cholesterol lowering effect. The beneficial anti-hypercholesterolaemic effect of whole dietary cluster beans as a source of dietary fibre was evaluated in high cholesterol diet induced hypercholesterolaemia in experimental rats. METHODS: Male Wistar rats (90-95 g) divided in six groups of 10 rats each were used. Freeze dried tender cluster beans were included at 12.5 and 25 per cent levels in the diet of animals maintained for 8 wk either on high (0.5%) cholesterol diet or basal control diet. RESULTS: Significant anti-hypercholesterolaemic effect was seen in cluster bean fed animals, the decrease in serum cholesterol being particularly in the LDL associated fraction. There was also a beneficial increase in HDL associated cholesterol fraction. Hepatic lipid profile showed a significant decrease in both cholesterol and triglycerides as a result of feeding tender cluster beans along with high cholesterol diet. INTERPRETATION & CONCLUSIONS: The present experimental results showed the beneficial hypocholesterolaemic and hypolipidimic influences dietary tender cluster beans in atherogenic situation. Studies in human need to be done to confirm the results.

Keller's arthroplasty in adults with hallux valgus and hallux rigidus.

BACKGROUND: The role of Keller's resection arthroplasty in the management of adult hallux valgus with hallux rigidus is debatable. There are no studies addressing this particular problem. METHODS: This study is a retrospective review of 32 patients (49 feet), conducted by an independent assessor. Subjective and objective criteria were used to assess the results of surgery. There were 30 women and 2 men with an average age at surgery of 62.5years. RESULTS: The results of surgery in terms of relief of pain, cosmesis and use of regular footwear were satisfactory. Excellent and good subjective results were obtained in 39% and 37% of cases respectively. Radiological analysis revealed decrease in the intermetatarsal and first metatarsophalangeal angle in a significant number of cases. Final results assessed by Vallier's modification of Bonney and MacNab criteria, revealed excellent to good results in 87% of feet. A significant number of complications were noted but there was no association between the occurrence of complications and the final result or the subjective functional grade. There was no association between the amount of resection of proximal phalanx and occurrence of metatarsalgia or the final outcome. CONCLUSION: The results of this study suggest that Keller's arthroplasty has a role in patients with adult hallux valgus associated with degenerative changes in the first metatarsophalangeal joint.

Alternaria tenuissima Causing Alternaria Blight on Pigeonpea in India.

Pigeonpea (Cajanus cajan (L.) Millsp.) is a major grain legume of the tropics and subtropics worldwide. In India, pigeonpea is the third most important food legume after chickpea and field pea. Blight symptoms on pigeonpea were observed in alarming proportion during the 2009 through 2011 crop seasons in Andhra Pradesh state in India. Disease incidence ranged from 20 to 80% irrespective of cultivars sown. Infected plants in the field showed symptoms on all aerial parts of the plant (leaves, stems, buds, and pods) irrespective of age of the plant and leaves. Symptoms on leaves were small, circular, necrotic spots that developed quickly forming typical concentric rings (1). Later, these spots coalesced and caused blighting of leaves. Spots were initially light brown and later turned dark brown. On stems, spots were sunken with concentric rings. In severe infection, defoliation and drying of infected leaves, branches, and flower buds was observed. The fungus was successfully isolated from all the infected plant parts (leaves, stem, buds, and pods) on potato dextrose agar (PDA) medium. After 4 to 5 days of incubation at 28 ± 1°C with a 12-h photoperiod, the fungus produced colonies that were regular and flat. The periphery of the colony was olive green with a black center. Monoconidial isolations were used to establish a pure culture of the fungus. Conidiophores were short, arising singly, and were 8.86 mm long and 2.97 mm thick. Conidia varied from 15.78 to 28.70 mm long and 8.03 to 13.47 mm wide. Very small beak (1.6 to 3.2 mm) or no beak was observed. Horizontal and vertical septations of conidia varied from four to six and two to four, respectively. The pathogenicity test was conducted on 8- to 10-day-old pigeonpea plants of cultivar ICPL 87119 by spraying with a conidial suspension (5 × 105 conidia/ml). Inoculated plants were covered with polythene bags and kept in a greenhouse at 28 ± 1°C with a 12-h photoperiod. After 48 h, the polythene bags were removed. Ten days after inoculation, symptoms were similar to those observed in fields. This experiment was conducted twice with two independent sets of plants. No symptoms were observed in water-inoculated control plants. The fungus was reisolated from the inoculated plants. On the basis of the morphological characteristics, the pathogen was tentatively identified as Alternaria tenuissima. The identification was further confirmed by the rDNA and internal transcribed spacer (ITS) primer. The ITS region of rDNA was amplified with ITS 1 and ITS 4 primers. Both orientation sequenced amplicons (481 bp) were submitted to GenBank (Accession No. JQ074094). A BLASTn search revealed 99% similarity to A. tenuissima (Accession No. HQ343444). To our knowledge, this is the first report of molecular identification of A. tenuissima causing Alternaria blight in pigeonpea in India. Reference: (1) Kannaiyan, J. and Nene, Y. L. 1977. Trop. Grain Legume Bull. 9:34.

Low bone mineral density in Indian patients with fragility fractures.

OBJECTIVE: Low bone mineral density (BMD) is a major risk factor for fragility fractures in osteoporosis. In recent studies, its use with clinical risk factors has been shown to enhance prediction of fragility fractures. The present study was done to assess BMD in Indian patients with fragility fractures using digital X-ray radiogrammetry (DXR-BMD). METHODS: A total of 228 patients (64 male and 164 female) admitted to an Orthopedic Hospital for management of fragility fracture were recruited. For each patient, DXR-BMD was obtained from an anteroposterior radiograph of the non-dominant hand. RESULTS: The number of subjects with hip fracture was 104 (40 male, 64 female). Vertebral fractures were seen in 67 patients (11 male, 56 female) and distal radial fracture in 57 patients (13 male, 44 female). The DXR-BMD (g/cm(2)) was significantly lower in subjects with any fragility fracture (0.51 vs. 0.58 in men and 0.41 vs. 0.54 in women). When compared to the age-matched normative reference data by decade, all subjects with fragility fracture had significantly lower DXR-BMD except male subjects in the age decade of 40-49 years. CONCLUSION: This study confirms lower DXR-BMD in Indian subjects with fragility fractures. This may have a potential role in fracture prediction when used with clinical risk factors in the Indian population.

The impact of VKORC1-1639 G>A polymorphism on the maintenance dose of oral anticoagulants for thromboembolic prophylaxis in North India: A pilot study.

BACKGROUND: The dose requirements for oral anticoagulants in thromboembolic events are influenced by promoter polymorphism in the VKORC1 gene. However, limited data are available on the influence of the polymorphism in various Indian populations. The present study aimed at determining the relationship between the VKORC1-1639 G>A genotypes and maintenance doses of oral anticoagulants for therapeutically stable INR values in patients taking Acitrom after valve replacement surgery. MATERIALS AND METHODS: Fifty patients from the northern Indian region were genotyped for VKORC1-1639 G>A by polymerase chain reaction and restriction fragment length polymorphism. Means of the weight-normalized daily Acitrom dose were calculated for every patient. RESULTS AND DISCUSSION: The VKORC1 1639G>A minor allele frequency in the study population (n = 50) was found to be 22%. The patients with a wild type genotype required the maximum drug dose as suggested for full functionality of the enzyme. Heterozygous patients were found to have an intermediate drug dose and the patients with a variant homozygous genotype had the minimum maintenance drug dose requirement. These findings are in concurrence with the effect of the promoter polymorphism on vitamin K epoxide reductase activity.1639G>A minor allele frequency in the study population (n = 50) was found to be 22%. The patients with a wild type genotype required the maximum drug dose as suggested for full functionality of the enzyme. Heterozygous patients were found to have an intermediate drug dose and the patients with a variant homozygous genotype had the minimum maintenance drug dose requirement. These findings are in concurrence with the effect of the promoter polymorphism on vitamin K epoxide reductase activity. CONCLUSION: The VKORC1-1639 G>A status can be indicative of establishing the therapeutic dose of oral anticoagulants in Indian patients.

Unusual cause of acquired brain injury.

A 37-year-old male was admitted with history of syncope and fall leading to right temporal bone fracture with extradural haemorrhage. He underwent craniotomy and clot evacuation. Postoperatively during inpatient rehabilitation, he was progressing well with his physical and cognitive rehabilitation, when he had resting tachycardia of between 90 and 100 per minute. Investigations to rule out cardio-pulmonary and endocrine causes of tachycardia were normal. He was further investigated for suspected postural orthostatic tachycardia syndrome (POTS). A tilt table test was done which revealed rise in baseline heart rate from 90/min to 130/min on 70 with no postural drop in blood pressure. Subsequently plasma norepinephrine level in erect posture was analysed which was 721 pg/ml. A working diagnosis of POTS was made. Initially, after an increase in water intake by 1.5-2 l/day, his baseline and postural tachycardia reverted back to 76/min. He is being followed up.

An ARF/CtBP2 complex regulates BH3-only gene expression and p53-independent apoptosis.

The alternative reading frame (ARF) tumor suppressor exerts both p53-dependent and p53-independent functions. The corepressor C-terminal binding protein (CtBP) interacts with ARF, resulting in proteasome-mediated degradation of CtBP. ARF can induce apoptosis in p53-null colon cancer cells, in a manner dependent on ARF interaction with CtBP. Bik was uniquely identified in an apoptotic gene array as coordinately upregulated in colon cancer cells after either CtBP2 knockdown or ARF overexpression. Validating the array findings, ARF induced Bik mRNA and protein expression, and this activity required an intact CtBP binding domain. Apoptosis induced by CtBP deficiency was substantially impaired when Bik expression was simultaneously silenced. An analysis of the Bik promoter revealed binding sites for the CtBP-interacting basic Kruppel-like factor (BKLF). A Bik promoter luciferase reporter was repressed by BKLF and CtBP2, and ARF reversed CtBP-associated repression. Chromatin immunoprecipitation analyses showed that CtBP was recruited to the Bik promoter largely by BKLF. Expression profiling of BH3-only gene expression in ARF-expressing or CtBP-deficient cells revealed that Bik was uniquely regulated by ARF/CtBP in colon cancer cells, whereas additional BH3-only proteins (Bim, Bmf) showed CtBP-dependent repression in osteosarcoma cells. ARF antagonism of CtBP repression of Bik and other BH3-only genes may have a critical role in ARF-induced p53-independent apoptosis and tumor suppression.

Keratotic vascular papules over the feet: a case of Waldenström's macroglobulinaemia-associated cutaneous macroglobulinosis.

Waldenström's macroglobulinaemia (WM) is a plasma-cell dyscrasia characterized by the monoclonal proliferation of lymphoplasmacytes. A 48-year-old man presented with a 4-year history of multiple painful, hyperkeratotic deep-seated papules over the pressure areas of both soles. He had a 1-year history of Raynaud's phenomenon, intermittent epistaxis, recurrent vomiting, tingling and numbness, and visual disturbances. Histological examination of a skin biopsy found amyloid-like deposits in the upper and mid dermis involving dermal blood vessels, but apart from periodic-acid-Schiff, various stains gave negative results for amyloid. Direct immunofluorescence was positive for IgM antibody. Hence, a diagnosis of WM with cutaneous macroglobulinosis was made. Immunoelectrophoresis found monoclonal IgM kappa antibody, and bone-marrow examination revealed a lymphoplasmacytoid malignancy. The patient's systemic systems were attributed to hyperviscosity syndrome associated with WM and the cutaneous papules were identified as deposits of excess IgM antibodies. The patient received five cycles of chemotherapy, resulting in nearly complete resolution of the skin lesions and systemic symptoms.

Essential thrombocythemia in a young man treated for myocardial infarction.

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm which can cause thrombohaemorrhagic complications usually involving microvasculature. Medium-sized arterial thrombosis has been reported, but coronary occlusion usually occurs with additional risk factors, for example, smoking, hyperlipidaemia and so on. We present a case of acute myocardial infarction (AMI) in a young man (29 years) with ET but without any coronary artery associated risk factors. He was successfully treated for his AMI and ET with cytoreductive treatment and has recovered well. Due to automated platelet counting, ET is being increasingly identified; early detection can prevent long-term complications, and patients can have normal life span.

Performance studies of ECORITE PAC-2010 as a coagulant in water treatment.

This paper describes the performance evaluation studies of ECORITE PAC-2010 of M/s Shriram Consolidated Limited (DSCL) as a coagulant. It was observed that ECORITE PAC-2010 acts as a good coagulant over a wide range of turbidity and produces larger and more rapidly settleable flocs than the alum. The residual aluminium is less in ECORITE PAC-2010 treated water than that in alum treated water. The sludge volume generated by ECORITE PAC-2010 is less than that generated by alum for attaining the same quality of settled water from turbid raw water.