GST is a family of enzymes that are important in protection of the body against oxidative stress.
Investigate the association between GSTT1 and GSTM1 polymorphism and hypertension.
Materials and Methods
GSTT1 and GSTM1 genotypes were detected by PCR. The fragments were then analyzed by agarose gel electrophoresis.
There is no significant association between GSTT1 & GSTM1 polymorphism and hypertension (OR = 2.4, P > 0.05 and OR = 1.6, P > 0.05)
GSTT1 & GSTM1 polymorphism can be considered a risk factor for hypertension.
Hypertension; Glutathione S-Transferase T1; Polymorphism, Genetic
Oral squamous cell carcinoma (OSCC) is the sixth most common cancer globally. Tobacco consumption and HPV infection, both are the major risk factor for the development of oral cancer and causes mitochondrial dysfunction. Genetic polymorphisms in xenobiotic-metabolizing enzymes modify the effect of environmental exposures, thereby playing a significant role in gene–environment interactions and hence contributing to the individual susceptibility to cancer. Here, we have investigated the association of tobacco - betel quid chewing, HPV infection, GSTM1-GSTT1 null genotypes, and tumour stages with mitochondrial DNA (mtDNA) content variation in oral cancer patients.
The study comprised of 124 cases of OSCC and 140 control subjects to PCR based detection was done for high-risk HPV using a consensus primer and multiplex PCR was done for detection of GSTM1-GSTT1 polymorphism. A comparative ΔCt method was used for determination of mtDNA content. The risk of OSCC increased with the ceased mtDNA copy number (Ptrend = 0.003). The association between mtDNA copy number and OSCC risk was evident among tobacco – betel quid chewers rather than tobacco – betel quid non chewers; the interaction between mtDNA copy number and tobacco – betel quid was significant (P = 0.0005). Significant difference was observed between GSTM1 - GSTT1 null genotypes (P = 0.04, P = 0.001 respectively) and HPV infection (P<0.001) with mtDNA content variation in cases and controls. Positive correlation was found with decrease in mtDNA content with the increase in tumour stages (P<0.001). We are reporting for the first time the association of HPV infection and GSTM1-GSTT1 null genotypes with mtDNA content in OSCC.
Our results indicate that the mtDNA content in tumour tissues changes with tumour stage and tobacco-betel quid chewing habits while low levels of mtDNA content suggests invasive thereby serving as a biomarker in detection of OSCC.
To study the immunomodulatory effect of ethanolic and aqueous extract of the rhizomes of Picrorrhiza kurroa (Scrophulariaceae) in normal and immunosuppressed mice models.
Materials and Methods:
The rhizomes extract of Picrorrhiza kurroa was administered orally according to their body weight in mice. The study was carried out by various hematological and serological tests. The assessment of immunomodulatory activity on specific and non-specific immunity was studied by administration of test extract. The method of cyclophasphamide-induced immunosuppression was employed with slight modification to study the immunomodulatory potential of the extract. Plant extracts were administered by oral feeding canula to the test groups (groups III–VI), group I (control animals) and group II (model control animals) received same volume of normal saline (0.2 ml). Humoral antibody response to SRBC measurement of antibody titer by hemagglutination reaction was done. The mice belonging to the all groups were antigenically challenged with SRBC (0.5×109 cells/ml/100 g) on 10th day intraparitoneally. Cellular immune response (Foot pad reaction test) the edema was induced by injecting SRBC (0.025×109 cells) in left paw, and 0.025 ml of saline was injected in right paw.
The plant extract showed protective effects on humoral immunity. The change in percentage deduction in footpad volume was also found significant (P<0.001). Administration of extract remarkably ameliorated both cellular and humoral antibody response.
It is concluded that the test extracts possessed promising immunostimulant properties. But, the alcoholic extract is more potent than aqueous extract in producing delayed type hypersensitivity response.
Hematological and serological tests; immunomodulatory activity; Picrorrhiza kurroa; rhizomes
Vinylation of aryl N-(2-pyridylsulfonyl) aldimines with versatile 1-alkenyl-1,1-borozinc heterobimetallic reagents is disclosed. In situ hydroboration of air-stable B(pin)-alkynes followed by chemoselective transmetallation with dimethylzinc and addition to aldimines provides B(pin)-substituted allylic amines in 60–93% yield in a one-pot procedure. The addition step can be followed by either B–C bond oxidation to provide α-amino ketones (71–98% yield) or Suzuki cross-coupling to furnish trisubstituted 2-arylated (E)-allylic amines (51–73% yield).
In the title compound, C16H15N3O3S, the dihedral angle between the aromatic rings is 8.18 (11)° and the C=N—N=C torsion angle is 178.59 (14)°. The conformation of the thiazine ring is an envelope, with the S atom displaced by 0.8157 (18) Å from the mean plane of the other five atoms (r.m.s. deviation = 0.045 Å). An intramolecular O—H⋯N hydrogen bond closes an S(6) ring. In the crystal, weak C—H⋯O interactions link the molecules, with all three O atoms acting as acceptors.
Auscultation of the heart is accompanied by both electrical activity and sound. Heart auscultation provides clues to diagnose many cardiac abnormalities. Unfortunately, detection of relevant symptoms and diagnosis based on heart sound through a stethoscope is difficult. The reason GPs find this difficult is that the heart sounds are of short duration and separated from one another by less than 30 ms. In addition, the cost of false positives constitutes wasted time and emotional anxiety for both patient and GP. Many heart diseases cause changes in heart sound, waveform, and additional murmurs before other signs and symptoms appear. Heart-sound auscultation is the primary test conducted by GPs. These sounds are generated primarily by turbulent flow of blood in the heart. Analysis of heart sounds requires a quiet environment with minimum ambient noise. In order to address such issues, the technique of denoising and estimating the biomedical heart signal is proposed in this investigation. Normally, the performance of the filter naturally depends on prior information related to the statistical properties of the signal and the background noise. This paper proposes Kalman filtering for denoising statistical heart sound. The cycles of heart sounds are certain to follow first-order Gauss–Markov process. These cycles are observed with additional noise for the given measurement. The model is formulated into state-space form to enable use of a Kalman filter to estimate the clean cycles of heart sounds. The estimates obtained by Kalman filtering are optimal in mean squared sense.
heart sound; murmurs; ECG; Kalman filters; acoustic cardiac signals
Actinomycosis is an infectious disease caused by anaerobic gram-positive, non-spore forming bacteria of the genus Actinomyces that affects the oropharynx, digestive tract, and genitalia. Thoracic actinomycosis may affect the respiratory tract and the pleura, even extending to the chest wall. Pulmonary actinomycosis occurs in immunocompetent persons during the fourth and fifth decades of life, with greater prevalence in men, and is generally due to Actinomyces israelii or A meyeri. It is frequently misdiagnosed as primary or metastatic lung cancer or conventional lung infections (eg, tuberculosis). The accepted predisposing factors for bronchopulmonary actinomycosis are poor dental hygiene, alcoholism and various chronic debilitating diseases, hiatus hernia, and gastro-oesophageal reflux. We report an interesting case of pulmonary actinomycosis presenting with haemoptysis, associated with achlasia cardia, and treated as tuberculosis.
Vaccines are the most effective public health intervention. Expanded Program on Immunization (EPI) provides routine vaccination in developing countries. However, vaccines that cannot be given in EPI schedule such as typhoid fever vaccine need alternative venues. In areas where school enrolment is high, schools provide a cost effective opportunity for vaccination. Prior to start of a school-based typhoid vaccination program, interviews were conducted with staff of educational institutions in two townships of Karachi, Pakistan to collect baseline information about the school system and to plan a typhoid vaccination program. Data collection teams administered a structured questionnaire to all schools in the two townships. The administrative staff was requested information on school fee, class enrolment, past history of involvement and willingness of parents to participate in a vaccination campaign.
A total of 304,836 students were enrolled in 1,096 public, private, and religious schools (Madrasahs) of the two towns. Five percent of schools refused to participate in the school census. Twenty-five percent of schools had a total enrolment of less than 100 students whereas 3% had more than 1,000 students. Health education programs were available in less than 8% of public schools, 17% of private schools, and 14% of Madrasahs. One-quarter of public schools, 41% of private schools, and 43% of Madrasahs had previously participated in a school-based vaccination campaign. The most common vaccination campaign in which schools participated was Polio eradication program. Cost of the vaccine, side effects, and parents' lack of information were highlighted as important limiting factors by school administration for school-based immunization programs. Permission from parents, appropriateness of vaccine-related information, and involvement of teachers were considered as important factors to improve participation.
Health education programs are not part of the regular school curriculum in developing countries including Pakistan. Many schools in the targeted townships participated in immunization activities but they were not carried out regularly. In the wake of low immunization coverage in Pakistan, schools can be used as a potential venue not only for non-EPI vaccines, but for a catch up vaccination of routine vaccines.
Vaccine; typhoid fever; developing country; infectious disease; health education
In this study honeycomb-like NiO nanostructures were grown on nickel foam by a simple hydrothermal growth method. The NiO nanostructures were characterized by field emission electron microscopy (FESEM), high resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD) techniques. The characterized NiO nanostructures were uniform, dense and polycrystalline in the crystal phase. In addition to this, the NiO nanostructures were used in the development of a zinc ion sensor electrode by functionalization with the highly selective zinc ion ionophore 12-crown-4. The developed zinc ion sensor electrode has shown a good linear potentiometric response for a wide range of zinc ion concentrations, ranging from 0.001 mM to 100 mM, with sensitivity of 36 mV/decade. The detection limit of the present zinc ion sensor was found to be 0.0005 mM and it also displays a fast response time of less than 10 s. The proposed zinc ion sensor electrode has also shown good reproducibility, repeatability, storage stability and selectivity. The zinc ion sensor based on the functionalized NiO nanostructures was also used as indicator electrode in potentiometric titrations and it has demonstrated an acceptable stoichiometric relationship for the determination of zinc ion in unknown samples. The NiO nanostructures-based zinc ion sensor has potential for analysing zinc ion in various industrial, clinical and other real samples.
honeycomb NiO nanostructures; potentiometric response; ion selective electrode; selectivity; selective ionophore
This study aims to train students on public health survey; correlate risk factors of osteoarthritis and to identify modifiable risk factors.
Osteoarthritis survey was carried out among 420 Bahraini women, above 40 years of age, diagnosed of osteoarthritis, attending ministry of health facilities.
Most cases in the study were from the age group of 50-59 years with a mean age of 57. Osteoarthritis: of major joints alone was 74%; of generalized was 21% and of small joints of hands and feet alone was 5%. Within major osteoarthritis: 48% were knees alone; 51% were knee and hip and 2% were hip alone. Combinations of co-morbidities were found among 43%. History of diagnosed: diabetes in 10%, hypertension among 13% and hypercholesterolemia in 5% of cases. Half of the cases in the study were obese and 30% were overweight. Osteoarthritis of the Knee and the combination of the osteoarthritis of knee and hip was highest among obese followed by overweight cases. Menopause was found among 68%of patients. Patients on medication accounted for 85% and 75% were on Physiotherapy. Half of the sample had family history of osteoarthritis. While over 90% were less educated with odds ratio for being housewives at 3.085. The multivariate analysis of ordinal regression returned pseudo R2 of 30% for the model with the following significant variables: age, BMI, menopause status, exercise, chronic morbidities and family history of osteoarthritis.
Overall, the proportion of major osteoarthritis of the weight bearing joints is very high. The modifiable risk factors identified from this study are sedentary lifestyle, obesity and overweight, as well as chronic morbidities.
Osteoarthritis; Risk factors; Public health audit; Ordinal regression
The incidence of difficulty in tracheal intubation has been reported to range from 0.5 to 18% in patients undergoing surgery. We aimed to elucidate the role of upper lip bite test (ULBT) with other prevailing tests, hyomental/thyrosternal distances (HMD/TSD), and the mandible length (ML) and their possible correlation in predicting difficulty in intubation. After institutional approval and informed consent were obtained, 300 consecutive patients aged 20–60 years of ASA physical status I and II, scheduled for elective surgical procedures requiring tracheal intubation and meeting the inclusion criteria, were enrolled in this study. Each patient was evaluated regarding ULBT, HMD, TSD and ML. Laryngoscopy was assessed by an attending anaesthesiologist blinded to the measurements. The laryngoscopic result was graded according to Cormack and Lehane’s Grading system. The negative predictive value (NPV) and positive predictive value (PPV) of ULBT were found to be 94 and 100%, respectively. These corresponding figures for TSD were 88.5 and 0%, respectively. Specificities for ULBT, HMD, ML and TSD were 100, 98.9, 98.9 and 98.1%, respectively. ULBT class and laryngoscopic grading showed the greatest agreement (kappa = 0.61, P < 0.001). An agreement between laryngoscopic grading and HMD and ML also existed (0.003 and <0.001, respectively), but was comparatively weaker. The high specificity, NPV, PPV and accuracy of ULBT as revealed in this study could be a good rationale for its application in the prediction of difficulty or easiness in intubation. ML > 9 cm and HMD > 3.5 cm were good predictors of negative difficult intubation.
Difficult intubation; difficult laryngoscopy; endotracheal intubation; predictive airway tests
Corrigendum to Acta Cryst. (2010), E66, o1881.
The name of one of the authors in the paper by Hussain et al. [Acta Cryst. (2010), E66, o1881] is corrected.
1-Alkenyl-1,1-heterobimetallics are potentially very useful in stereoselective organic synthesis, but are relatively unexplored. Introduced herein is a practical application of 1-alkenyl-1,1-heterobimetallic intermediates in the synthesis of versatile cyclopropyl alcohol boronate esters, which are valuable building blocks. Thus, hydroboration of 1-alkynyl-1-boronate esters with dicyclohexylborane generates 1-alkenyl-1,1-diboro species. In situ transmetalation with dialkylzinc reagents furnishes 1-alkenyl-1,1-borozinc heterobimetallic intermediates. Addition of the more reactive Zn–C bond to aldehydes generates the key B(pin) substituted allylic alkoxide intermediates. An in situ alkoxide directed cyclopropanation proceeds with the formation of two more C–C bonds, affording cyclopropyl alcohol boronate esters with three new stereocenters in 58–89% isolated yields and excellent diastereoselectivities (>15:1 dr). Oxidation of the B–C bond provides trisubstituted α-hydroxycyclopropyl carbinols as single diastereomers in excellent yields (75–93%). Facile pinacol-type rearrangement of the α-hydroxycyclopropyl carbinols provides access to both cis- and trans-2,3-disubstituted cyclobutanones with high stereoselectivity (>17:1 dr in most cases) from a common starting material. This methodology has been applied in the synthesis of quercus lactones A and B.
Chronic hepatitis C (CHC) is one of the commonest infectious diseases of the liver and may lead to cirrhosis or hepatocellular carcinoma. Combination therapy with pegylated interferon (PEG-IFN) and Ribavirin is the treatment of choice for CHC. Combination therapy is thought to act by means of antiviral mechanisms and immunomodulation. Thyroid dysfunction is the most common autoimmune adverse effect associated with combination therapy; hypothyroidism is more common than hyperthyroidism. Antithyroid antibodies and female sex have a predictive value in the development of interferon induced thyroid disease (IITD). Patients with CHC should be informed of the possibility of side effects on the thyroid gland. Screening for antithyroid antibodies and thyroid function tests should be performed in patients with CHC before the commencement of antiviral treatment, and during and after it. This article reviews different aspects of IITD, including its pathogenesis, clinical manifestations, association with treatment regimens and treatment response and the outcome of thyroid dysfunction.
Chronic Hepatitis C; Interferon; Ribavirin; Thyroid Disease
Sister Mary Joseph nodule or Sister Mary Joseph Sign refers to a palpable nodule bulging into the umbilicus as a result of metastasis of a malignant cancer in the pelvis or abdomen. A rare case of Sister Mary Joseph nodule, manifesting as ascites, cachexia and bleeding per rectum, is presented without any primary tumor despite extensive search for the same.
Umbilical Nodule; Metastasis; FNAC
This is a case report of acute L3/4 vertebral osteomyelitis due to Salmonella paratyphi A confirmed by culture from vertebral needle biopsy. From a review of the literature this is the first reported case with bacteriological confirmation. The rarity of Salmonella paratyphi spondylitis and the options for treatment are discussed.
Spondylitis; Salmonella Paratyphi
Molecules of the title compound, C14H10FN3O, are essentially planar and in the crystal structure they form dimers via hydrogen bonds, involving pyrimidinyl N atoms and amino H atoms, about inversion centers. The centroids of the furyl and pyrimidinyl rings are separated by 3.489 (2)Å, indicating π–π stacking interactions.
Recurrence and reflux are 2 most important remote complications of lap-paraesophageal hernia (PEH) repair. However, the extent of recurrence remains unknown. We sought to determine the true incidence of recurrence after lap-PEH repair.
A meta-analysis was carried out. PubMed, EMBASE, Cochrane Library, hand search, and personal communication were used to access and appraise studies. The inclusion criteria were full-text papers published from 1991 to date that describe lap-PEH repair in >25 patients, have at least a 6-month follow-up, and address the issue of recurrence. “Wrap migration” papers were excluded. Papers were appraised and the data were isolated on summary sheets. MS Office Excel 2003 was used to plot the results and represent it in graphs.
Thirteen studies were eligible (all retrospective case series). A total of 965 patients with 99 recurrences were noted. The overall recurrence rate (in all patients) was 10.2% and was 14% if only the followed up patients (n=658/965) were considered. However, when patients with objective evidence (follow-up Ba esophagogram) were used (301/965), the “true” recurrence rate was 25.5% (ie, 1 in 4 recurred). The learning curve did not appear to be an issue (P=0.27). The studies revealed broad 95 CI and touched the line-of-no-effect, thereby increasing the “chance factor.” When an alternate model was applied, esophageal lengthening (by Collis-Nissen gastroplasty) revealed a significant protective influence (P<0.0001).
The true incidence of lap-PEH recurrence is 25.5%. The learning curve is not an adequate explanation. Mandatory (protocol) follow-up esophagograms at 1 year are essential. Two emphasis points in the repair have emerged: hiatoplasty and (superadded) esophageal lengthening.
Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates processes including mRNA translation, proliferation, and survival. By assembling with different cofactors, mTOR forms two complexes with distinct biological functions. Raptor-bound mTOR (mTORC1) governs cap-dependent mRNA translation, whereas mTOR, rictor, and mSin1 (mTORC2) activate the survival and proliferative kinase Akt. How the balance between the competing needs for mTORC1 and -2 is controlled in normal cells and deregulated in disease is poorly understood. Here, we show that the ubiquitin hydrolase UCH-L1 regulates the balance of mTOR signaling by disrupting mTORC1. We find that UCH-L1 impairs mTORC1 activity toward S6 kinase and 4EBP1 while increasing mTORC2 activity toward Akt. These effects are directly attributable to a dramatic rearrangement in mTOR complex assembly. UCH-L1 disrupts a complex between the DDB1-CUL4 ubiquitin ligase complex and raptor and counteracts DDB1-CUL4-mediated raptor ubiquitination. These events lead to mTORC1 dissolution and a secondary increase in mTORC2. Experiments in Uchl1-deficient and transgenic mice suggest that the balance between these pathways is important for preventing neurodegeneration and the development of malignancy. These data establish UCH-L1 as a key regulator of the dichotomy between mTORC1 and mTORC2 signaling.
IL-17A induces the release of pro-inflammatory cytokines and of reactive oxygen species which could lead to neutrophilic inflammation. We determined the role of IL-17 receptor (IL-17R) signalling in oxidant-induced lung emphysema and airway hyperresponsiveness. IL-17R−/− and wild-type C57/BL6 mice were exposed to ozone (3 ppm; 3 hours) for 12 times over 6 weeks. Bronchial responsiveness to acetylcholine was measured, and lungs were retrieved. Mean linear intercept (Lm) and isometric contractile responses of intrapulmonary airways to acetylcholine were determined. In wild-type mice but not in IL-17R−/−, chronic ozone exposure caused airway hyperresponsiveness. The increase in Lm after chronic ozone exposure of wild-type mice was also observed in IL-17R−/− mice. The increased maximal contractile response to acetylcholine seen in airways of wild-type mice exposed to ozone was abolished in IL-17R−/− mice. p38-mitogen-activated protein kinase (MAPK) and dexamethasone-dependent increase in contractile response was reduced in airways from IL-17R−/− ozone-exposed mice. Lung inflammation scores were not altered in IL-17R−/− mice exposed to ozone compared to wild-type mice. The increased release of IL-17 and IL-1β, and the activation of p38 MAPK in the lungs of ozone-exposed mice was reduced in IL-17R−/− mice. IL-17R signalling underlies the increase in airway hyperresponsiveness seen after ozone exposure, mediated by the increased contractility of airway smooth muscle. The emphysema and lung inflammation induced by ozone is not dependent on IL-17.
The authors report a sudden painless blindness in a 42-year-old male with membranous nephropathy of idiopathic origin. He was admitted with a history of decreased urine output and painful abdomen of a 3-day duration in the Department of Nephrology, Sheri Kashmir Institute of Medical Sciences, Srinagar, Kashmir – a tertiary care centre in the state of Jammu and Kashmir, India. On evaluation, he was found to have renal vein thrombosis. On day 3 of admission, he suddenly developed progressive painless blindness. Indirect ophthalmoscopic examination showed retinal vein thrombosis. Patient's clinical condition deteriorated due to his underlying condition and he succumbed to his illness. Renal vein thrombosis as a complication of nephrotic syndrome is well known. To the best of our knowledge, this is the first case of retinal vein thrombosis in the course of nephrotic syndrome.
Although renal impairment has been described in COPD, there is opportunity to evaluate further to determine nature and consider optimal management. Increased aortic stiffness, as seen in COPD, leads to reduced buffering of pulsatile flow. We hypothesised that urinary albumin creatinine ratio (UACR) would reflect glomerular damage related to aortic stiffness.
Patients with COPD and controls underwent spirometry, blood pressure, arterial stiffness - aortic pulse wave velocity (PWV) and provided a spot urine sample for UACR, with other renal biomarkers measured.
The UACR was increased in patients (n = 52): 0.80 mg/mmol compared to controls (n = 34): 0.46 mg/mmol, p < 0.05. Aortic PWV was related to log10 UACR in all subjects (r = 0.426, p < 0.001) and COPD patients alone. Aortic PWV was a significant variable for UACR with oxygen saturations, after accounting for potential confounders. Eight subjects (7 patients) reached a defined clinical microalbuminuria threshold, with aortic PWV greater in these patients compared to those patients without, although albuminuria is a continuum. Proximal tubular damage biomarkers, unlike the glomerular marker, were not different between patients and controls.
There is glomerular damage in patients with COPD evidenced by increased UACR, related to increased aortic stiffness. Besides the macrovascular prognostic implications of increased aortic stiffness, the microvascular state in COPD management should be considered.
Arterial stiffness; Biomarkers; Haemodynamics; Kidney; Renal; Microvascular
In addition to its genetic function, DNA is one of the most distinct and smart self-assembling nanomaterials. DNA nanotechnology exploits the predictable self-assembly of DNA oligonucleotides to design and assemble innovative and highly discrete nanostructures. Highly ordered DNA motifs are capable of providing an ultra-fine framework for the next generation of nanofabrications. The majority of these applications are based upon the complementarity of DNA base pairing: adenine with thymine, and guanine with cytosine. DNA provides an intelligent route for the creation of nanoarchitectures with programmable and predictable patterns. DNA strands twist along one helix for a number of bases before switching to the other helix by passing through a crossover junction. The association of two crossovers keeps the helices parallel and holds them tightly together, allowing the assembly of bigger structures. Because of the DNA molecule's unique and novel characteristics, it can easily be applied in a vast variety of multidisciplinary research areas like biomedicine, computer science, nano/optoelectronics, and bionanotechnology.
DNA; Nanotechnology; Biomedicine; Nanoelectronics; Nanosensors; DNA computation