Prevalence of unsuspected glucose intolerance in coronary artery disease (CAD) patients: Importance of HbA1c.

BACKGROUND: The mortality and morbidity rates are two to fourfold higher among Coronary Artery Disease (CAD) patients with type 2 diabetes mellitus (DM). American Diabetes Association (ADA) and World Health Organization (WHO) define different criteria for the diagnosis of glucose intolerance. This study compares the available diagnostic criteria for DM in Indian men and their importance in CAD patients. METHODS: This cross-sectional study was done on 794 male volunteers; 483 individuals from general population and 311 patients undergoing angiography for evaluation of CAD. Individuals with previous clinical history of diabetes mellitus were excluded. RESULTS: More than 90% of diabetics by ADA criteria could be diagnosed by Fasting plasma glucose (FPG) and HbA1c criteria while FPG and pg2h plasma glucose (WHO criteria) could detect only 74%. Impaired Fasting Glucose (IFG) or Impaired Glucose Tolerance (IGT) was present in 36.7% of individuals diagnosed to be diabetic based on HbA1c; more in CAD +ve group (53.8%) than in general population (23.6%). ROC analysis suggests >121 mg/dl of FPG or >6.2% of HbA1c as optimum cut-off for the diagnosis of DM. FPG and HbA1c criteria have higher Relative Risk for presence of coronary artery occlusion and HOMA-IR. CONCLUSION: Inclusion of HbA1c in the criteria for diagnosis of DM (ADA criteria) can detect large number of cases with persistent hyperglycemia in the non-diagnostic range of DM (IFG or IGT) among general population and CAD patients. This has special relevance to epidemiological studies as the diagnosis of DM can be made on single fasting blood sample.

Successful co-administration of a human rotavirus and oral poliovirus vaccines in Bangladeshi infants in a 2-dose schedule at 12 and 16 weeks of age.

Co-administration of oral live-attenuated human rotavirus vaccine RIX4414 (Rotarix) and oral polio vaccine (OPV) was assessed. Healthy infants were randomised to receive 2-doses of either: RIX4414 or placebo co-administered with OPV (12 and 16 weeks of age); or RIX4414 or placebo given 15 days after OPV. After vaccination, 56.5-66.7% of RIX4414 and 18.6% of placebo recipients had seroconverted for rotavirus IgA. No significant differences between RIX4414 groups with or without OPV co-administration were observed. No statistically significant differences were observed between groups for polio seroprotection rates. RIX4414 vaccine was immunogenic when co-administered with OPV and did not interfere with OPV seroprotection rates.

Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a).

Coccidioides posadasii spherules stimulate macrophages to make cytokines via TLR-2 and Dectin-1. We used formalin-killed spherules and 1,3-beta-glucan purified from spherules to stimulate elicited peritoneal macrophages and myeloid dendritic cells (mDCs) from susceptible (C57BL/6) and resistant (DBA/2) mouse strains. DBA/2 macrophages produced more TNF-alpha and IL-6 than macrophages from C57BL/6 mice, and the amount of TNF-alpha made was dependent on both TLR2 and Dectin-1. DCs from C57BL/6 mice made more IL-10 and less IL-23p19 and IL-12p70 than did DBA/2 DC. These responses were inhibited by a monoclonal antibody to Dectin-1. DBA/2 mice expressed full-length Dectin-1, whereas C57BL/6 mice spliced out exon 3, which encodes most of the stalk. RAW cells transduced to express the full-length Dectin-1 responded better to FKS than cells expressing truncated Dectin-1. We compared the isoform of Dectin-1 expressed by 34 C57BL/6 X DBA/2 recombinant inbred (BXD RI) lines with their susceptibility to Coccidioides immitis. In 25 of 34 RI lines susceptibility or resistance corresponded to short or full-length isoforms, respectively. These results suggest that alternative splicing of the Dectin-1 gene contributes to susceptibility of C57BL/6 mice to coccidioidomycosis, and affects the cytokine responses of macrophages and mDCs to spherules.

Vaccination greatly reduces disease, disability, death and inequity worldwide.

In low-income countries, infectious diseases still account for a large proportion of deaths, highlighting health inequities largely caused by economic differences. Vaccination can cut health-care costs and reduce these inequities. Disease control, elimination or eradication can save billions of US dollars for communities and countries. Vaccines have lowered the incidence of hepatocellular carcinoma and will control cervical cancer. Travellers can be protected against "exotic" diseases by appropriate vaccination. Vaccines are considered indispensable against bioterrorism. They can combat resistance to antibiotics in some pathogens. Noncommunicable diseases, such as ischaemic heart disease, could also be reduced by influenza vaccination. Immunization programmes have improved the primary care infrastructure in developing countries, lowered mortality in childhood and empowered women to better plan their families, with consequent health, social and economic benefits. Vaccination helps economic growth everywhere, because of lower morbidity and mortality. The annual return on investment in vaccination has been calculated to be between 12% and 18%. Vaccination leads to increased life expectancy. Long healthy lives are now recognized as a prerequisite for wealth, and wealth promotes health. Vaccines are thus efficient tools to reduce disparities in wealth and inequities in health.

Immunogenicity and safety of combined diphtheria tetanus whole cell pertussis hepatitis B/ Haemophilus influenzae type b vaccine in Indian infants.

OBJECTIVE: To evaluate the immunogenicity of the Hepatitis B and Haemophilus influenzae type b components and the overall safety and reactogenicity of the DTPw-HBV/Hib vaccine when given as primary vaccination to Indian infants. DESIGN AND METHODS: At 3 centers in India, 225 healthy infants (who had received HBV at birth) received three doses of DTPw-HBV/Hib vaccine at 6, 10 and 14 weeks of age. Serum anti-HBs and anti-PRP antibody levels were measured prior to vaccination and one month post dose 3. Solicited local and general symptoms reported during the 4-day follow-up period and unsolicited adverse event reported during the 30-day follow-up period after each dose were recorded. Serious adverse events were recorded throughout the study. RESULTS: A total of 219 subjects completed the study. 2.7% and 11.5% of all administered doses led to redness and swelling >20 mm, respectively; only 3.6% of doses were followed by severe pain (cried when limb was moved, spontaneously painful) within 4 days after vaccination. Fever exceeding 39.5C was recorded following only one dose in one subject. The percentage of doses followed by severe solicited general symptoms (symptoms that prevented normal activity) did not exceed 0.8%. Two SAEs were reported, neither of which were considered as related to vaccination. One month post-dose 3, all subjects had seroprotective antiPRP antibody concentrations (> or =0.15 microgram/mL) and 98.6% had concentrations > or =1 microgram/mL; 99% were seropositive for antiHBs (concentrations > or = 3 mIU/mL) and 99% were seroprotected (concentrations > or = 10 mIU/mL). CONCLUSION: The combination DTPw-HBV/Hib vaccine is immunogenic (for the antigens tested), safe and well tolerated in Indian infants.

Safety and reactogenicity of a low dose diphtheria tetanus acellular pertussis vaccine (Boostrix) in pre-school Indian children.

OBJECTIVE: To evaluate the safety and reactogenicity of a reduced-antigen-content combined Diphtheria Tetanus Acellular Pertussis (dTpa) vaccine in Indian preschool children. METHODS: GlaxoSmithKline Biologicals combination dTpa vaccine was administered as a single booster dose to 347 children aged 46 years in seven centers across India. All children were subsequently followed up for two weeks for safety and reactogenicity assessment. RESULTS: A total of 345 subjects completed the study and two subjects were lost to follow-up. One serious adverse event (head injury) unrelated to vaccination was reported. Otherwise, all subjects were in good health throughout the study period. Three subjects (0.9%) reported transient general symptoms (such as irritability and drowsiness), which prevented normal activity. Pain at injection site, swelling and redness was reported in 31.1%, 18.2% and 8.9% subjects respectively. Five subjects (1.4%) reported severe pain preventing normal movement. This resolved within 48 hours in all cases. There were no other severe local reactions including large injection site reactions. CONCLUSION: The reduced antigen content combined dTpa vaccine is safe and well tolerated in Indian pre-school children.

Development of NaCl-tolerant strain in Chrysanthemum morifolium Ramat. through in vitro mutagenesis.

One NaCl-tolerant chrysanthemum (Chrysanthemum morifolium Ramat.) variant (E2) has been developed in a stable form through IN VITRO mutagenesis using ethylmethane sulfonate (EMS) as the chemical mutagen. Salt tolerance was evaluated by the capacity of the plant to maintain both flower quality and yield under stress conditions. Enhanced tolerance of the E2 variant has been attributed to the increased activity of superoxide dismutase (SOD), ascorbate peroxidase (APX), and dehydroascorbate reductase (DHAR), and, to a lesser extent of membrane damage than NaCl-treated control plants. Isoform analysis revealed that an increase in total SOD activity in the E2 variant was solely due to significant activation of the Cu/Zn isoform. Elevated levels of carotenoids and ascorbate in E2 leaves have been reflected in their higher free radical scavenging capacity (RSC) expressed in terms of DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging ability. Data reflect that a proper balance between enzymatic and non-enzymatic defence systems is required for combating salinity stress in chrysanthemum. Better performance of the E2 progeny under same salinity stress condition, even in the second year, confirms the genetic stability of the salt-tolerance character. On the whole, the E2 variant, developed through 0.025 % EMS treatment, might be considered as a NaCl-tolerant strain showing positive characters towards NaCl stress.

Molecular characterization of marker-free transgenic lines of indica rice that accumulate carotenoids in seed endosperm.

A single Agrobacterium strain harbouring two binary plasmids was successfully used for the first time to develop a marker-free transgenic rice of improved nutritional value. Sixty-eight T0 co-transformants were obtained in three indica rice cultivars--two popular high-yielding Bangladeshi varieties (BR28 and BR29), and one high-iron rice cultivar (IR68144). Marker-free lines were obtained from 14 out of 24 selected co-transformants screened in the T1 generation. The accumulation of total carotenoids in polished T2 rice seeds of the primary transgenic VPBR29-17-37 reached levels of up to 3.0 microg/g, with the level of beta-carotene reaching 1.8 microg/g. In the cultivars BR28 and IR68144, total carotenoid levels in the transformants reached 2.0 microg/g of polished rice seeds. The levels of lutein and other carotenoids in the seeds were also significantly enhanced. T1 plants obtained from primary transgenics with simple gene-integration patterns tended to have a lower carotenoid content than the original parental lines. This study describes the development of marker-free transgenic rice lines containing high levels of carotenoids, and addresses the relationship between the rearrangement of transgenes and the presence of metabolic end products in transgenic rice.

Analgesic, antiinflammatory and CNS depressant activities of sesquiterpenes and a flavonoid glycoside from Polygonum viscosum.

Analgesic, antiinflammatory and CNS depressant activities of four sesquiterpenes, viscosumic acid, viscozulenic acid, viscoazucine and viscoazulone, and a flavonoid glycoside, quercetin-3-O-(6''-feruloyl)-beta-D-galactopyranoside isolated form the aerial parts of Polygonum viscosum (Polygonaceae) have been assessed. All test compounds exhibited CNS depressant activity in open field test, all but viscoazulone showed analgesic activity in Eddy's hot plate test, all sesquiterpenes inhibited acetic acid induced abdominal writhing in mice, and all but viscoazucine and the flavonoid glycoside exhibited mild to moderate antiinflammatory effect on carrageenan induced rat paw edema.

In vitro activity of cefazolin and ampicillin.

An in vitro antimicrobial sensitivity of Cefazolin and Ampicillin towards 85 strains of Staphylococcus aureus and 52 strains of Esch. Coli was carried out by Kirby-Baurer's Technique at Microbiology Dept. Nepalgunj Medical College, Nepal. 47% Staphylococcus aureus and 25% Esch. coli. were found sensitive to Cefazolin where as sensitivity pattern of Ampicillin was 19% and 7.74% respectively.

Amplatzer Device closure of Atrial Septal Defects and Patent Ductus Arteriosus: Initial Experience.

Surgical closure of Atrial Septal Defects (ASD) and Patent Ductus Arteriosus (PDA) can be performed successfully with low mortality. However, the morbidity associated with general anaesthesia, thoracotomy, cardiopulmonary bypass, postoperative monitoring in the intensive care unit, several days of hospital stay and the requirement of blood products is considerable. The expense associated with this morbidity, operative scar and the psychologic trauma to the patient and parents are additional disadvantages of surgery. Hence, the closure of these defects by transcatheter methods with various devices has been evaluated worldwide. We report the initial experience at our centre with closure of secundum ASDs and large PDAs with the Amplatzer Septal Occluder and Amplatzer Duct Occluder.

Elastic guided waves in a layered plate with rectangular cross section.

Guided waves in a layered elastic plate of rectangular cross section (finite width and thickness) has been studied in this paper. A semianalytical finite element method in which the deformation of the cross section is modeled by two-dimensional finite elements and analytical representation of propagating waves along the length of the plate has been used. The method is applicable to arbitrary number of layers and general anisotropic material properties of each layer, and is similar to the stiffness method used earlier to study guided waves in a laminated composite plate of infinite width. Numerical results showing the effect of varying the width of the plate on the dispersion of guided waves are presented and are compared with those for an infinite plate. In addition, effect of thin anisotropic coating or interface layers on the guided waves is investigated.

Dominant NZB contributions to lupus in the (SWR x NZB)F1 model.

(SWR x NZB)F1 (or SNF1) mice succumb to lupus nephritis. Analysis of NZB x SNF1 backcross mice has recently revealed the existence of four dominant SWR loci (H2 on Chr 17, Swrl-1 on Chr 1, Swrl-2 on Chr 14 and Swrl-3 on Chr 18), and two NZB loci (Nba1 and Lbw2/Sbw2, both on Chr 4) conferring lupus susceptibility. The present study focusing on a panel of 88 SWR x SNF1 backcross mice reveals the existence of five suggestive loci for antinuclear antibody formation, consisting of three dominant NZB contributions (Nba4 on Chr 5, Lbw4 on Chr 6, and Nba5 on Chr 7), and two recessive SWR contributions (Swrl-1 on Chr 1, and Swrl-4 on Chr 10). In addition, this study reveals a dominant NZB locus for GN (Nba3 on Chr 7, peak at 31 cM), and a dominant NZB locus linked to early mortality, on Chr 10 (peak at 4 cM). Collectively, these studies suggest that lupus in the SNF1 strain is the epistatic end-product of four dominant SWR loci and four dominant NZB loci. The immunological functions and molecular identities of these loci await elucidation.

Angioplasty for chronic total coronary occlusions: safety and efficacy.

OBJECTIVE: To determine the short term results and safety of angioplasty in chronic coronary occlusions. METHODS: Eighty consecutive patients undergoing percutaneous transluminal coronary angioplasty (PTCA) for chronic coronary occlusions were prospectively analyzed for acute success rate and safety of the procedure. RESULTS: The mean age was 46.7 years (range 30-78 years). There were 72 males and eight females. Clinical presentation was recent myocardial infarction (MI) in four cases (5%), unstable angina in 20 (25%), chronic stable angina in 24 (30%) and past history of MI in 32 (40%) cases. Vessel distribution was left anterior descending artery (LAD) in 40 (50%), left circumflex artery (LCx) in 12 (15%) and right coronary artery (RCA) in 28 (35%) cases. Lesion length varied from 8 mm to 37 mm with a mean of 16.7 mm. Acute success rate was 70% (56/80). Twenty four cases (30%) had unsuccessful result due to failure to cross with wire (18 cases) or inability to cross with the balloon (six cases). One major complication in the form of type III coronary perforation was encountered which was successfully managed surgically. CONCLUSION: Percutaneous transluminal coronary angioplasty (PTCA) in chronic total occlusion has a reasonable success rate and very low complication rate.

Pyramiding transgenes for multiple resistance in rice against bacterial blight, yellow stem borer and sheath blight.

Here we describe the development of transgene-pyramided stable elite rice lines resistant to disease and insect pests by conventional crossing of two transgenic parental lines transformed independently with different genes. The Xa21 gene (resistance to bacterial blight), the Bt fusion gene (for insect resistance) and the chitinase gene (for tolerance of sheath blight) were combined in a single rice line by reciprocal crossing of two transgenic homozygous IR72 lines. F4 plant lines carrying all the genes of interest stably were identified using molecular methods. The identified lines, when exposed to infection caused by Xanthomonas oryzae pv oryzae, showed resistance to bacterial blight. Neonate larval mortality rates of yellow stem borer ( Scirpophaga incertulas) in an insect bioassay of the same identified lines were 100%. The identified line pyramided with different genes to protect against yield loss showed high tolerance of sheath blight disease caused by Rhizoctonia solani.

Genetic contributions of nonautoimmune SWR mice toward lupus nephritis.

(SWR x New Zealand Black (NZB))F(1) (or SNF(1)) mice succumb to lupus nephritis. Although several NZB lupus susceptibility loci have been identified in other crosses, the potential genetic contributions of SWR to lupus remain unknown. To ascertain this, a panel of 86 NZB x F(1) backcross mice was immunophenotyped and genome scanned. Linkage analysis revealed four dominant SWR susceptibility loci (H2, Swrl-1, Swrl-2, and Swrl-3) and a recessive NZB locus, Nba1. Early mortality was most strongly linked to the H2 locus on chromosome (Chr) 17 (log likelihood of the odds (LOD) = 4.59 - 5.38). Susceptibility to glomerulonephritis was linked to H2 (Chr 17, LOD = 2.37 - 2.70), Swrl-2 (Chr 14, 36 cM, LOD = 2.48 - 2.71), and Nba1 (Chr 4, 75 cM, LOD = 2.15 - 2.23). IgG antinuclear autoantibody development was linked to H2 (Chr 17, LOD = 4.92 - 5.48), Swrl-1 (Chr 1, 86 cM, colocalizing with Sle1 and Nba2, LOD = 2.89 - 2.91), and Swrl-3 (Chr 18, 14 cM, LOD = 2.07 - 2.13). For each phenotype, epistatic interaction of two to three susceptibility loci was required to attain the high penetrance levels seen in the SNF(1) strain. Although the SWR contributions H2, Swrl-1, and Swrl-2 map to loci previously mapped in other strains, often linked to very similar phenotypes, Swrl-3 appears to be a novel locus. In conclusion, lupus in the SNF(1) strain is truly polygenic, with at least four dominant contributions from the SWR strain. The immunological functions and molecular identities of these loci await elucidation.

Isolation and structure elucidation of viscoazucine, a novel sesquiterpene from Polygonum viscosum.

A new sesquiterpene, 1,4-dimethoxycarbonyl-7-(1-methylethyl)- 3,3a,6,7,8,8a-hexahydroazulene (viscoazucine) (1), and a known flavone, 3',5,7-trihydoxy-3,4',5'-trimethoxyflavone (4), have been isolated from Polygonum viscosum. The structures of these compounds were elucidated by spectroscopic analyses, notably UV, MS and NMR.

Immunostimulatory DNA-based vaccines elicit multifaceted immune responses against HIV at systemic and mucosal sites.

Immunostimulatory DNA sequences (ISS, also known as CpG motifs) are pathogen-associated molecular patterns that are potent stimulators of innate immunity. We tested the ability of ISS to act as an immunostimulatory pathogen-associated molecular pattern in a model HIV vaccine using gp120 envelope protein as the Ag. Mice immunized with gp120 and ISS, or a gp120:ISS conjugate, developed gp120-specific immune responses which included: 1) Ab production; 2) a Th1-biased cytokine response; 3) the secretion of beta-chemokines, which are known to inhibit the use of the CCR5 coreceptor by HIV; 4) CTL activity; 5) mucosal immune responses; and 6) CD8 T cell responses that were independent of CD4 T cell help. Based on these results, ISS-based immunization holds promise for the development of an effective preventive and therapeutic HIV vaccine.