Rapidly enlarging mycotic coronary artery aneurysm caused by bacterial seeding involving methicillin-sensitive Staphylococcus aureus and Klebsiella pneumoniae.

Coronary artery aneurysms are uncommon. A rare subcategory caused by infectious etiologies are called mycotic coronary artery aneurysms (MCAA), which have an exceedingly high mortality rate. In this report, we present a rare case of a rapidly expanding MCAA involving Staphylococcus aureus and Klebsiella pneumoniae affecting the left circumflex artery. Per our literature review, MCAA involving K. pneumoniae co-infection or superinfection have rarely, if ever, been documented. The aneurysm was discovered when the patient underwent coronary angiography for non-ST-elevation myocardial infarction. She was treated for bacteremia and upon reevaluation the aneurysm had grown approximately three times the original size. The patient had an aneurysmectomy with coronary artery bypass grafting due to the enlargement and size of the aneurysm. By highlighting this life-threatening disease, we hope to shed light on rare causes of MCAA and the importance of appropriate treatment. .

Evaluation of DNA segments in 2'-modified RNA sequences in designing efficient splice switching antisense oligonucleotides.

Synthetic antisense oligonucleotides (ASOs) have emerged as one of the most promising therapeutic approaches. So far, nine ASO drugs have received approval for clinical use, and four of them are based on splice-switching principles demonstrating the impact of ASO-mediated splice modulation. Notably, three among them (Exondys 51, Vyondys 53 and Viltepso) are based on phosphorodiamidate morpholino (PMO) chemistry whereas Spinraza is based on 2'-O-methoxyethyl phosphorothioate (2'-MOE PS) chemistry. Although systemic delivery of PMOs has displayed a good safety profile even at high doses, the 2'-O-methyl phosphorothioate modified (2'-OMe PS) ASO drug candidate (drisapersen) failed due to safety issues. The potency of 2'-modified RNA for splice-switching needs to be further improved by novel design strategies for broad applicability. Towards this goal, in this study, we evaluated the potential of incorporating DNA segments at appropriate sites in 2'-OMe PS and 2'-MOE PS ASOs to induce exon skipping. For this purpose, a four-nucleotide DNA segment was systematically incorporated into a 20-mer 2'-OMe PS and 2'-MOE PS ASO designed to skip exon 23 in mdx mouse myotubes in vitro. Our results demonstrated that 2'-modified RNA PS ASOs containing four or less PS DNA nucleotides at the 3'-end yielded improved exon 23 skipping efficacy in line with fully modified ASO controls. Based on these results, we firmly believe that the present study opens new avenues towards designing splice modulating ASOs with limited chemical modifications for enhanced safety and therapeutic efficacy.

A simple purification procedure of buffalo lung cathepsin H, its properties and influence of buffer constituents on the enzyme activity.

BACKGROUND: Cathepsin H (E.C.3.4.22.16) belongs to a family of lysosomal cysteine protease which regulates diverse normal biological processes mainly in intracellular proteolysis. METHODS: Purification of cathepsin H from an unstudied system i.e. buffalo lung has been achieved by a simple process developed after incorporating appropriate alteration in the available methods for isolation of the enzyme from other sources. The use of DEAE-Cellulose and SP-Sephadex C-50 helped in better and simultaneous separation of cathepsin B and H up to homogeneity. RESULTS: The SDS-PAGE result showed buffalo cathepsin H to be a single-chain molecule having MW, NH2- and COOH- terminal residues of 25.4 kDa, Lys and Val respectively. The enzyme was a glycoprotein with pI of 6.2; it hydrolyzed Leu-NA (Vmax/Km = 301.6) as the most efficient substrate followed by Arg-NA, Arg-Arg-NA and BANA. Buffalo enzyme showed maximum activity at 36 °C, pH 6.75 and at a buffer concentration of 2 × 10-3 M. CONCLUSION: Catheptic activity was found to be quite stable at least for 20-30 min between pH 4.5-7.0, buffer concentration of 1 × 10-2 to 4 × 10-2 M and the temperature resistance up to 36 °C. The effects of various substances present in the buffers routinely used for the assay of catheptic activity revealed that the activity of buffalo lung cathepsin H depends not only qualitatively but also quantitatively on the constituents of assay buffer. GENERAL SIGNIFICANCE: This study seems to provide valuable information regarding the biochemistry of cathepsin H in general as well as influence of buffer constituents on enzyme activity and physiological role in particular.

Role of apoplastic calcium during germination and initial stages of seedling establishment in Vigna radiata seeds.

Calcium (Ca2+) is implicated in the initial phase of seed germination and seedling establishment. It is stored complexed with phytic acid during seed development and released by phytase action during germination. We observed phytase activity 18 h post-imbibition (PI) in Vigna seeds, while radicle protrusion occurred approximately 12 h PI. Cotyledon protein extracts prepared 4, 8, 16 and 24 h PI, subjected to Ca2+ immobilized metal affinity chromatography (Ca2+ IMAC), revealed the presence of Ca2+ binding proteins (CaBPs), while Ca2+-dependent amylase activity peaked 18 h PI, implying Ca2+ presence before its release from Ca-phytate, indicating an alternative source of Ca2+. Vigna cotyledon cell-wall preparations 4 h and 24 h PI, titrated against alkali, revealed high cation-binding capacity, and seeds 4 h PI demonstrated high rates of H+ extrusion. Ca2+-binding capacity as well as cell-wall bound Ca2+, measured in cotyledon cell-wall preparations from unimbibed seeds as well as seeds 24 h PI, using a novel competitive chelation technique, showed a marked decline in Ca2+ binding capacity, as well as cell-wall bound Ca2+. Imbibition in the presence of chelators, Ca2+-channel blockers, and H+-pump inhibitors, interfered with germination and radical extension. Further, EDTA-treated cotyledon protein extracts separated on Ca2+IMAC showed a larger CaBP peak than control cotyledon extracts. Pooled fractions clearly showed Ca2+-induced extrinsic fluorescence with anilino -napthalene sulfonate. The results strongly implicate the apoplast may be a major source of Ca2+ in the initial phase of germination and seedling establishment in Vigna seeds.

Feasibility and acceptance of oral human papillomavirus detection in the dental office: Results from The National Dental Practice-Based Research Network.

BACKGROUND: Oral human papillomavirus (HPV) infection is the principal underlying cause of a dramatic increase in oropharyngeal cancer. Dentistry can play an important role in developing clinical algorithms for secondary prevention. METHODS: The authors conducted this cross-sectional pilot study with practices of The National Dental Practice-Based Research Network. The authors evaluated the feasibility and acceptability of screening and testing procedures as judged by practitioners and patients. The authors used tablet devices for patient screening, obtaining consent, and administering a confidential oral HPV risk factor survey. RESULTS: Most patients (85%) were comfortable being asked about their cigarette use and their sexual behavior (69%) and were interested in participating again (79%). More than 90% of practitioners were comfortable with study procedures except the extra time required for patient participation (75% comfortable). There were no problems with oral rinse collection as reported by patients or practitioners. CONCLUSIONS: It is feasible in community dental offices to collect oral rinses for HPV detection and to ask patients explicit questions about sexual history when using a tablet device for confidentiality. PRACTICAL IMPLICATIONS: Discussing high-risk types of HPV and appropriately assessing that risk are a challenge for oral health care professionals. These results are positive from a research perspective but do not address the advisability of routine HPV screening in dentistry.

Inhibition of Heat Shock proteins HSP90 and HSP70 induce oxidative stress, suppressing cotton fiber development.

Cotton fiber is a specialized unicellular structure useful for the study of cellular differentiation and development. Heat shock proteins (HSPs) have been shown to be involved in various developmental processes. Microarray data analysis of five Gossypium hirsutum genotypes revealed high transcript levels of GhHSP90 and GhHSP70 genes at different stages of fiber development, indicating their importance in the process. Further, we identified 26 and 55 members of HSP90 and HSP70 gene families in G. hirsutum. The treatment of specific inhibitors novobiocin (Nov; HSP90) and pifithrin/2-phenylethynesulfonamide (Pif; HSP70) in in-vitro cultured ovules resulted in a fewer number of fiber initials and retardation in fiber elongation. The molecular chaperone assay using bacterially expressed recombinant GhHSP90-7 and GhHSP70-8 proteins further confirmed the specificity of inhibitors. HSP inhibition disturbs the H2O2 balance that leads to the generation of oxidative stress, which consequently results in autophagy in the epidermal layer of the cotton ovule. Transmission electron microscopy (TEM) of inhibitor-treated ovule also corroborates autophagosome formation along with disrupted mitochondrial cristae. The perturbations in transcript profile of HSP inhibited ovules show differential regulation of different stress and fiber development-related genes and pathways. Altogether, our results indicate that HSP90 and HSP70 families play a crucial role in cotton fiber differentiation and development by maintaining cellular homeostasis.

Dietary supplementation of n-3 polyunsaturated fatty acid alters endometrial expression of genes involved in prostaglandin biosynthetic pathway in breeding sows (Sus scrofa).

The present investigation was designed to study the effect of dietary supplementation of omega-3 (n-3) PUFA on endometrial expression of fertility-related genes in breeding sows. Sixteen crossbred sows were randomized to receive diets containing 4% (wt/wt) flaxseed oil as n-3 PUFA source (TRT group) or iso-nitrogenous, iso-caloric standard control diet (CON group), starting from the first day of estrus up to 40 days and were artificially bred on the second estrus. Endometrial samples were collected during days 10-11 and 15-16 post-mating for studying relative expression profile of candidate genes viz. Prostaglandin F Synthase (PGFS), microsomal Prostaglandin E Synthase-1 (mPGES-1) and Carbonyl Reductase-1 (CBR-1) using quantitative Real-Time PCR. Expression level of mPGES-1 gene transcript was 2.1-fold higher (P < 0.05) during 10-11 days of pregnancy and 1.4-fold higher (P > 0.05) during 15-16 days of pregnancy in TRT group as compared to CON group. Relative expression of PGFS gene transcript was significantly lower (P < 0.05) during 10-11 days of pregnancy in TRT group while there was no significant effect (P > 0.05) of dietary supplementation during 15-16 days of pregnancy. Endometrial mRNA level of CBR1 was significantly lower (P < 0.05) with 3.93-fold decrease in TRT group during 10-11 days of pregnancy whereas 2.82-fold reduction in expression (P > 0.05) was observed subsequently during 15-16 days of pregnancy as compared to CON group. Collectively, these results indicate that dietary n-3 PUFA supplementation can modulate gene expression of key enzymes in prostaglandin biosynthetic pathway during early gestation, which in turn might have beneficial impact on overall reproductive response in breeding sows. These findings partly support strategic dietary supplementation of plant-based source of n-3 PUFA with an aim to improve overall reproductive performance in sows.

Uttar Pradesh Association of Physicians of India Position Statement: Betel Quid (Paan) and Diabetes.

Betel quid (paan) chewing is common in India, especially in Uttar Pradesh. Betel quid has multifaceted relationship with health, including metabolic and psychosocial health. The current recommendations have been released keeping in view the public health and clinical importance of this addictive behavior. The objective of this document is to offer clinical guidance for screening, diagnosis and management of co-occurring betel quid chewing among persons with Diabetes Mellitus (DM). The document aims to provide education and guidance to clinicians engaged in care and management of persons with DM, and improve access to treatment for co-occurring betel quid chewing among persons with DM. The current recommendation grades are based on published evidence, and categorized as strong, intermediate, weak and no evidence. The strength of these recommendations is based on the level of evidence.

Uttar Pradesh Association of Physicians of India Position Statement: Tobacco Use and Metabolic Syndrome.

Tobacco use is one of the main preventable causes of mortality and morbidity worldwide. The global disease burden due to tobacco use is huge with projected mortality of eight million lives per year by 2030. Metabolic syndrome (MS) is defined as a constellation of cardiovascular and endocrine risk factors such as insulin resistance, obesity, raised blood pressure, and abnormal lipid profile. The relationship between tobacco use and MS has been well established. Also, the causal association between tobacco use and development of individual components of MS is well established. The Uttar Pradesh Association of Physicians of India (UP API) has drafted this position statement on managing tobacco use among persons with or at risk of developing Metabolic Syndrome (MS). This position statement presents evidence-based recommendations as described below. Scope and purpose The objective of this position statement is to offer clinical recommendations for screening, diagnosis and management of tobacco use among persons with or at risk of developing Metabolic Syndrome (MS). The purpose of this document is to aid in identification and treatment of maladaptive patterns of tobacco use i.e. tobacco use disorder (tobacco dependence, harmful use, abuse) in person with or at risk of developing MS. Intended Audience The position statement is targeted at the clinicians engaged in care and management of person with or at risk of developing Metabolic Syndrome (MS). This might also be of relevance to the policy makers considering the public health burden of both MS and tobacco use disorders.

Development of parthenote following in vivo transfer of embryos in Capra hircus.

The aim of this study is to generate parthenogenetic embryos from chemically activated in vitro matured caprine oocytes and to study the in vivo developmental potency of such embryos. The parthenogenetic embryos (2-8 and 16 cells to morula stage) were surgically transferred in 26 recipients. Pregnancy in recipients following embryo transfer was monitored by ultrasonography. The recipient aborted a foetus on day 34 post transfer. Sexing of parthenogenetic foetus showed a single band of amelogenin gene indicating female cell DNA. Microsatellite analysis revealed that the recipient has not contributed genetically to the parthenogenetic foetus confirming the identity of aborted foetus of parthenogenetic origin. The authors believe that this is the first authentic report on in vivo development of parthenogenetic foetus in Capra hircus.

Impact of norgestomet supplementation during early luteal phase on subsequent luteal profiles and conception rate in buffalo: a preliminary study.

The current study was aimed to establish the impact of progesterone supplementation (norgestomet progestagen) between days 4 to 10 post-ovulation on subsequent luteal profile and conception rate in buffaloes. The 28 Murrah buffaloes of second to fourth parity, having normal reproductive organs, were estrus synchronized by double PGF(2α) protocol at 11 days apart. The buffaloes were inseminated during mid- to late estrus and thereafter repeated at 24 h interval. The buffaloes were randomly assigned into two groups: (1) control (no treatment, n = 14) and (2) treatment group (CRESTAR ear implant, n = 14). The CRESTAR ear implant (3 mg, norgestomet progestagen) was inserted subcutaneous between days 4 to 10 post-ovulation. The ovaries were scanned at estrus and thereafter on days 4, 10, 16, 21, and 40 post-ovulation to examine the preovulatory follicle (POF) and corpus luteum (CL) diameter. Each ultasonography was followed by blood sample collection for analysis of plasma progesterone concentrations following ovulation. The conception rate was similar (p > 0.05) between treated and control buffaloes. The pregnant buffalo of the control group had larger (p < 0.05) POF diameter than nonpregnant counterparts. The CL diameter was similar (p > 0.05) in both treated and untreated control as well as in their pregnant and nonpregnant buffaloes of the respective groups. The plasma progesterone concentrations were higher (p < 0.05) in the treatment group on the day 10 post-ovulation as compared to the control buffaloes. It is concluded that norgestomet supplementation had no impact on conception rate and CL diameter but enhances the plasma progesterone concentrations following treatment in buffaloes.

Groundwater contaminated with hexavalent chromium [Cr (VI)]: a health survey and clinical examination of community inhabitants (Kanpur, India).

BACKGROUND: We assessed the health effects of hexavalent chromium groundwater contamination (from tanneries and chrome sulfate manufacturing) in Kanpur, India. METHODS: The health status of residents living in areas with high Cr (VI) groundwater contamination (N = 186) were compared to residents with similar social and demographic features living in communities having no elevated Cr (VI) levels (N = 230). Subjects were recruited at health camps in both the areas. Health status was evaluated with health questionnaires, spirometry and blood hematology measures. Cr (VI) was measured in groundwater samples by diphenylcarbazide reagent method. RESULTS: Residents from communities with known Cr (VI) contamination had more self-reports of digestive and dermatological disorders and hematological abnormalities. GI distress was reported in 39.2% vs. 17.2% males (AOR = 3.1) and 39.3% vs. 21% females (AOR = 2.44); skin abnormalities in 24.5% vs. 9.2% males (AOR = 3.48) and 25% vs. 4.9% females (AOR = 6.57). Residents from affected communities had greater RBCs (among 30.7% males and 46.1% females), lower MCVs (among 62.8% males) and less platelets (among 68% males and 72% females) than matched controls. There were no differences in leucocytes count and spirometry parameters. CONCLUSIONS: Living in communities with Cr (VI) groundwater is associated with gastrointestinal and dermatological complaints and abnormal hematological function. Limitations of this study include small sample size and the lack of long term follow-up.

Genetic predisposition for dermal problems in hexavalent chromium exposed population.

We studied the effect of genetic susceptibility on hexavalent chromium induced dermal adversities. The health status of population was examined from the areas of Kanpur (India) having the elevated hexavalent chromium levels in groundwater. Blood samples were collected for DNA isolation to conduct polymorphic determination of genes, namely: NQO1 (C609T), hOGG1 (C1245G), GSTT1, and GSTM1 (deletion). Symptomatic exposed subjects (n = 38) were compared with asymptomatic exposed subjects (n = 108) along with asymptomatic controls (n = 148) from a non contaminated reference community. Exposed symptomatic group consisted of 36.8% subjects who were GSTM1 null genotyped as compared to asymptomatic where only 19.4% subjects were null. The exposed subjects with GSTM1 null genotype were more susceptible to dermal adversities in comparison with wild genotyped subjects (OR = 2.42; 95% CI = 1.071-5.451). Age, smoking, gender or duration of residence were not found to have any confounding effect towards this association. Association with other genes was not statistically significant, nonetheless, possible contribution by these genes cannot be ruled out. In conclusion, variation in the polymorphic status of GSTM1 gene may influence dermal outcomes among residents from Cr(VI) contaminated areas. Further studies are therefore, needed to examine these observations among different population groups.

Interferon stimulated gene 15 (ISG15): molecular characterization and expression profile in endometrium of buffalo (Bubalus bubalis).

Interferon stimulated gene 15 (ISG15), one of the several proteins induced by conceptus derived Type I and/or a Type II interferon (IFN), is implicated as an important factor in determining the uterine receptivity and conceptus development. However, presence as well as specific role of the ISG15 in buffalo (Bubalus bubalis) reproduction is yet to be elucidated. In the present study, both genomic and cDNA sequences of bubaline (bu) ISG15 were cloned and investigated for its expression in different tissues of female reproductive tract of buffalo. Sequence analysis revealed 100% identity among the genomic sequences (1014 bp) of buISG15 from three different breeds of buffalo (viz., Murrah: Acc. No. DQ118137, Mehsana: Acc. No. DQ118138, and Nagpuri: Acc. No. DQ118136) and cDNAs (Acc. Nos. HM543268-HM543270). As in cattle, the buISG15 was comprised of two exons of 57 bp and 520 bp encoding a peptide of 154 amino acids. Moreover, the buISG15 cDNA sequence exhibited 98.3% and 98.5% identity with that of taurine and indicine cattle, respectively. Subsequent reverse transcription PCR analysis revealed expression of the buISG15 in the uterine endometrium, corpus luteum (CL), corpus hemorrhagicum and oviduct. Quantitative Real Time PCR (RTqPCR) analysis also confirmed the constitutive expression of the buISG15 in the uterine endometrium during different stages (i.e. estrus, diestrus and proestrus) of estrous cycle and also during early (∼d 30-40) pregnancy. Western blot analysis of the endometrial extract from both estrous cyclic as well as pregnant buffalo demonstrated the presence of only conjugated ISG15 which was >40 kDa. ISG15 mRNA and immune-reactive proteins were localized in the stromal as well as glandular epithelial cells of the uterine endometrium of estrous cyclic as well as pregnant buffalo. However, there was no significant difference in amount of ISG15 mRNA across the different reproductive phases. To conclude, this study will be helpful for the further understanding of the roles of the ISG15 in pregnancy of buffalo cows.

Molecular characterization and expression profile of uterine serpin (SERPINA14) during different reproductive phases in water buffalo (Bubalus bubalis).

Uterine serpins (SERPINA14) play important roles during pregnancy in the farm animals. In this study, we have cloned and characterized cDNA sequence encoding the bubaline SERPINA14. We also studied its spatio-temporal expression in the uterine endometrium. The bubaline SERPINA14 has an open reading frame of 1299bp. Itshares ∼90% identity with the SERPINA14 of other ruminant livestock species. Phylogenetically, bubaline SERPINA14 has been placed in the same clade that contained other mammalian homologues with a maximum identity to bovine SERPINA14. Using an anti-ovine monoclonal antibody, Western blot analysis of the uterine fluid of buffalo during the early stage of pregnancy confirmed the presence of SERPINA14 of about 48,000Da. The results of quantitative real time PCR (RT-qPCR) as well as in situ hybridization demonstrated a stage and tissue specific expression of bubaline SERPINA14. The level of SERPINA14 mRNA was low during stage I (Days 3-5), which increased (P<0.05) during stage II (Days 6-15) and then subsequently declined during stage III (Days 16-21) of the estrus cycle. During early pregnancy (Days ∼30 of gestation) the level of SERPINA14 mRNA was as high as that during stage II of the estrus cycle. The SERPINA14 mRNA was localized in the glandular epithelium. The differential spatio-temporal expression of SERPINA14 in the uterine endometrium of buffalo suggests its plausible important roles in reproduction.

GSTM1, GSTT1, and GSTP1 polymorphism in north Indian population and its influence on the hydroquinone-induced in vitro genotoxicity.

Glutathione S transferase (GST) gene polymorphism examined among north Indians and correlated with hydroquinone (HQ) genotoxicity to help in clinical prediction of susceptibility of HQ toxicity. Lymphocytes of individuals with/without GSTM1, GSTT1, and GSTP1 (ile/ile or val/val) were exposed to HQ (20, 40, or 80 microM) and examined chromosomal aberrations (CA) or cytokinesis-block micronucleus assays. Among north Indians the frequencies of GSTM1 (null), GSTT1 (null), and both null were found to be 41.1, 21.9, and 12.7%, whereas frequencies of GSTP1 with (ile/ile) or (ile/val), or (val/val) were 52, 42.1, or 5.9%, respectively. Individuals with null GSTM1, GSTT1, and GSTP1 (val/val) showed inhibition of mitotic index (MI) and significant (p < 0.01) induction of CA as compared to individuals with GSTM1, GSTT1, and GSTP1 (ile/ile). Micronucleus formation was found to be significant (p < 0.05 or 0.01) in both the genotypes. Results indicate that GSTM1, GSTT1 (null), and GSTP1 (val/val) are sensitive to HQ genotoxicity.

Study of genetic polymorphism in solvent exposed population and its correlation to in vitro effect of trichloroethylene on lymphocytes.

Trichloroethylene (TCE) is major industrial pollutant that contaminate environment. Its exposure may lead to hepato-renal toxicity along with the cancer progression. Although extensive research is done on its toxicity still not much is known about its genotoxic potential on humans in relation to genetic polymorphism. Cytochrome P450 (CYP P-450) and glutathione-S-transferases (GSTs) are important in cellular detoxification of TCE. Variations in gene sequences result in population specific regional genetic variations (polymorphism). Genotyping of CYP1A1, GSTM1, GSTT1 and GSTP1 polymorphism was performed in 220 normal and 97 solvent-exposed individuals from northern part of India using real time PCR, PCR and restriction digestion techniques. The parameters examined to study genotoxicity were chromosomal aberration (CA) and cytokinesis block micronucleus assay (CBMN) in lymphocyte culture in vitro. The observed average frequencies for GSTM1 (null) and GSTT1 (null) were 41, 22 and 12.7%, respectively in normal subjects whereas frequencies of CYP1A1/GSTP1 with (ile/ile) or (ile/val) or(val/val) were found to be 76.2/52, 21.4/42.1 and 2.4/5.9% respectively. It was further observed that the frequencies of above genes were found to be similar in solvent exposed groups. The distribution frequencies of GST genes, when compared with other reports from various regions of India show variations. In vitro TCE exposure (2, 4 and or 6 mM) did not show any significant genotoxic effect. TCE maybe toxic due to its metabolite.

Lung cancer risk in north Indian population: role of genetic polymorphisms and smoking.

Lung cancer (LC) is the leading cause of cancer-related mortality in developing as well as developed countries. Life style choices, particularly tobacco smoking, have been implicated as the main cause in the development of the LC. Despite the fact that majority cases of the LC occur among smokers, only 1-15% of smokers develop LC. In the present study, we have explored the role of genetic polymorphism, smoking habit and their association to LC in a cohort of north Indian population. The polymorphic genes explored were CYP1A1, GSTM1, GSTP1 and GSTT1 using techniques of Polymerase chain reaction (PCR), Restriction Fragment Length Polymorphism (RFLP), Real Time PCR (RT PCR), and gene sequencing. Genetic polymorphism was analysed in 253 normal participants (control) and 93 LC patients originating from Lucknow, India. Data were compared using odds ratio and Fisher Exact Test. We found that smoking increases the susceptibility to LC threefold (OR = 2.9; 95% CI: 0.9-2.8). The most significant risk for LC (OR = 3.2; 95% CI: 0.7-3.8) was found in the association of the homozygous variant of CYP1A1 gene at A2455G base change at Exon 7 (Val/Val) genotype. There was a marginally significant association between LC and GSTT1 null genotype (OR = 1.3; 95% CI: 1.0-1.7) while no significant risk association was found between GSTP1 polymorphism and LC. The present study demonstrates that the presence of null genotype of GSTM1/GSTT1 taken together with CYP1A1 (Val/Val) genotype increases the susceptibility to LC eightfold in comparison to CYP1A1 (Ile/Ile) and GSTM1/ GSTT1 genotype.

High nasopharyngeal carriage of beta-lactamase-negative ampicillin-resistant Haemophilus influenzae in north Indian school-going children.

Development of ampicillin resistance in Haemophilus influenzae is a cause of serious concern. Ampicillin resistance in H influenzae is beta-lactamase mediated except in some isolates. Two important issues related to beta-lactamase-negative ampicillin-resistant (BLNAR) strains while choosing therapy for infections caused by H. influenzae are (i) whether BLNAR H. influenzae isolates are sufficiently pathogenic to cause respiratory tract infection, and (ii) variability in the magnitude of ampicillin minimum inhibitory concentrations obtained for the isolates. The aim of the present study was to determine the carriage of BLNAR H. influenzae in the nasopharynx of normal healthy children, to test the level of ampicillin resistance and the correlation of ampicillin resistance with resistance to other antimicrobials and to evaluate the frequency of serotype b and biotypes I, II, and III among BLNAR H. influenzae. Of 1001 H. influenzae isolates, 229 (22.9%) strains were ampicillin resistant. A total of 33/229 isolates were BLNAR. beta-Lactamase-positive strains show higher level of resistance to ampicillin as well as to chloramphenicol, erythromycin, and co-trimoxazole. Of the 196 beta-lactamase-producing H. influenzae isolates, 112 (57%) were H. influenzae type b, while of the 33 BLNAR isolates, 27 (81.8%) were H. influenzae type b. One hundred and eighty-four of 196 (93.9%) beta-lactamase-producing H. influenzae isolates and 30/33 (91.0%) BLNAR strains belonged to biotypes I, II, and III. BLNAR H. influenzae are no less pathogenic than beta-lactamase-positive H. influenzae. Higher level of drug resistance was found in beta-lactamase-producing H. influenzae in comparison to BLNAR isolates.