Role of Glut-1 in Tumor Progression and Prognosis in Oral Squamous Cell Carcinoma: A Systematic Review

Introduction: Oral cancer, one of the most common cancers worldwide constitutes a major public health problem and is one of the leading cancer sites among men and women in India. Increased uptake of glucose in cancer cells are mediated by glucose transporters. Among 14 isoforms of glucose transporters, Glucose transporter 1 (GLUT-1) isoform expression predominate Oral squamous cell carcinoma (OSCC). Aim: To emphasize the expression of GLUT-1 in OSCC and to assess its role in tumor progression and prognosis. Materials and Methods: Hand searching and electronic databases such as PubMed/Medline, Google scholar and Science- Direct were done for mesh terms such as OSCC, GLUT-1, prognosis, tumor markers, prognostic marker and risk predictor. Studies were pooled and relevant articles were evaluated. Results: Final analysis identified thirteen articles after considering the inclusion and exclusion criteria. These studies evalu- ated 926 OSCC cases and 70 healthy controls for GLUT-1 immunoexpression. The data was extracted and evaluated manu- ally. GLUT-1 expression was found to be elevated in OPMDs and OSCC than in healthy controls. The pattern of expression of GLUT-1, its correlation with clinico-pathological features, role in tumour progression and prognosis, expression in tumor invasive front, correlation with other markers and role in therapeutics are also discussed in detail

A study to assess knowledge of primary health workers on malaria epidemiology, diagnosis, and treatment in Patiala district, India

Background: India accounts for (4%) of all malaria cases worldwide. The World malaria report 2017 showed that, by 2016, global progress against malaria had stalled and was off track to meet the Global Technical Strategy milestones for 2020. Aims and Objectives: The aim of the study is to assess knowledge of rural medical officers (RMO) and health workers on malaria epidemiology, diagnosis, and treatment as per National Vector Borne Disease Control Program of India guidelines. Materials and methods: A descriptive, observational, and cross-sectional study was done among government health personnel’s using a semi-structured questionnaire. Results: In the present study, 258 health personnel’s participated comprising multipurpose health workers female (MPHW-F), multipurpose health worker male (MPHW-M), and RMO. The standardized score on knowledge of vector biology and epidemiology was 72% and 54% for RMO and (MPHW-M), respectively. On malaria diagnosis, MPHW-M has got median score (53%) as compared to RMO (46%). On national malaria drug policy, there is a marginal difference between median score of RMO (42%) and MPHW-M (40%). Overall, there is incomplete and poor knowledge of treatment of malaria among all health personnel’s with lack of concept about presumptive treatment. Training showed some positive impact on the knowledge of MPHW-F but no impact on MPHW-M. Graduates and experienced workers have got better knowledge than undergraduates and MPHW-M have more knowledge than MPHW-F. There is poor knowledge of reporting formats, and usage of rapid diagnostic kits among all the health personnels. There was no significant impact of education qualification, in service training and work experience on the knowledge of Male health workers. Conclusion: Training needs to be suitably tailored as there is a lot of scope of improvement in the knowledge regarding malaria diagnosis and treatment among health workers.

A study to assess the association between early childhood caries and relationship of Streptococcus mutans in saliva of mother, child and sibling pairs

Background: Early childhood caries (ECC) is a specific form of rampant caries that initially affects the primary maxillary anterior teeth of infants and children.' According to American Academy of Pediatric Dentistry (AAPD) 2011, early childhood caries is defined as the presence of one or more decayed (non-cavitated or cavitated lesions), missing (due to caries) or filled tooth surfaces in any primary tooth in a child under the age of six. The objective of this study was to assess the association between early childhood caries and relationship of Streptococcus mutans in saliva of mother, child and sibling pairs.Methods: Group 1 consists of fifty children with early childhood caries along with their mothers and siblings with the child age between 15 months to 5 years and sibling's age between 4 years to 10 years, whereas group 2 consists of fifty caries free children along with their mothers and siblings. For both groups, saliva samples were taken from the child, mother and sibling pairs to estimate the Streptococcus mutans count and to determine pH of saliva in these children. DMFT scores, debris scores checked for child, mother and sibling pairs.Results: Streptococcus mutans count was significantly high in group 1 than that of the group 2. Mothers were more co related to the children in the acquisition of Streptococcus mutans than the siblings. Increased no of meals of the child, pacifier use, low socio-economic status and low maternal education showed significant high correlation with caries prevalence. Low pH score was also significantly correlated with the increase in caries rate.Conclusions: Maternal factors such as high DMFT scores, low education levels, prolonged bottle-feeding with sweetened milk, pacifier use are strong risk indicators for identifying high caries-susceptible children.

Effect of vitamin E supplementation with standard treatment on oxidant-antioxidant status in chronic obstructive pulmonary disease.

BACKGROUND & OBJECTIVES: Chronic oxidant burden and depletion of endogenous antioxidants have been proposed to play a key role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Exogenous antioxidants have potential therapeutic implications and their role has not been explored in COPD. The objective of this study was to investigate the effect of supplementation of standard treatment (inhaled long-acting beta(2) agonists, anticholinergics and corticosteroids) with vitamin E on oxidant-antioxidant balance in patients with COPD. METHODS: The study was carried out in the outpatient setting. Patients were divided into two groups: group A- placebo group (n=14), receiving only standard therapy, and group B- vitamin E-supplemented group (n=10), receiving 400 IU of vitamin E capsules twice daily in addition to standard therapy. Spirometry and clinical assessment were carried out at the start and completion of 8 wk treatment along with measurements of several biochemical parameters of oxidant-antioxidant status in plasma, leukocytes and red cells separated from venous blood. RESULTS: Leukocyte superoxide generation was decreased in both the groups. Vitamin E-supplemented group had significantly increased levels of plasma sulphydryls and red cell catalase while the placebo group had decreased levels of plasma nitrates and nitrites. No significant differences were observed in red cell superoxide dismutase and glutathione peroxidase activities, total blood glutathione, and plasma total antioxidant capacity, lipid peroxides and glutathione peroxidase activity in either group. There was a similar degree of lung function and clinical improvement in both the groups. INTERPRETATION & CONCLUSION: Our findings showed that an 8 wk supplementation of standard treatment with 400 IU twice daily of vitamin E did not provide any additional clinical benefit although it augmented certain endogenous antioxidants in patients with COPD.

Targeting protein acetylation for improving cancer therapy.

Acetylation is one of the most important post-translational modification of proteins determining the structure, function and intracellular localization that plays an important role in the signal transduction pathways related to diverse cell functions, both during unstimulated and stress conditions. Protein acetylation in cells is regulated by a co-ordinated action of histone acetyl transferases (HAT) and histone deacetylases(HDAC) that ensures the maintenance of homeostasis and execution of activities related to damage response viz. DNA repair, cell cycle delay, apoptosis and senescence. Since inhibition of histone deacetylation, stalls the progress of many nuclear events including proliferation and damage response events on the one hand and the levels of deacetylases are elevated in many tumours on the other. Histone deacetylase has been among the targets for the development of anticancer drugs and adjuvant. The recent observation showing acetylation of proteins by calreticulin (an endoplasmic reticulum resident protein) with a high efficiency when polyphenolic acetates are the acetyl group donating molecules and acetyl CoA as weak substrate extends the realm of protein acetylation beyond HAT/HDAC combination. Elucidation of the relative roles of HAT/HDAC mediated acetylation viz. a calreticulin mediated acetylation in cell function under a variety of stress conditions would hold key to the design of drugs targeting protein acetylation system.

Effect of sensitization on membrane ion fluxes & intracellular calcium in guineapigs.

BACKGROUND & OBJECTIVES: The biochemical mechanisms underlying the development of sensitization-induced airway hyperresponsiveness (AHR) in asthma are poorly defined. Alterations in the regulation of intracellular calcium may play an important role in its pathogenesis. We carried out this study to see the effect of sensitization with ovalbumin on membrane ion fluxes and intracellular calcium in a guinea pig model. METHODS: Airway reactivity to inhaled histamine was measured initially and after sensitization with ovalbumin in 28 guineapigs. Intracellular calcium [Ca(2+)]i was measured in tracheal smooth muscle cells and peripheral leukocytes using fluorescent dye FURA 2AM. Calcium and sodium ion influx across the cell membrane was measured in leukocytes. Ouabain-sensitive Rubidium ((86)Rb) influx was measured in tracheal smooth muscles cells. The activities of Na(+), K(+) ATPase and Ca(2+) ATPase were measured in tracheal smooth muscle cells. Lipid peroxides were measured in plasma. RESULTS: Airway responsiveness was significantly (P<0.001) increased after sensitization along with an increase in [Ca2+]i levels in leukocytes and tracheal smooth muscle cells, higher rates of (45)Ca and (22)Na influx in leukocytes and higher (86)Rb influx rates in tracheal smooth muscle cells, and increased levels of lipid peroxides in plasma. INTERPRETATION & CONCLUSION: In guineapig model of asthma sensitization to allergen increased the membrane permeability to calcium and sodium, and intracellular calcium levels. These alterations may play a role in the pathogenesis of airway hyper-responsiveness following sensitization.

Suicidal oxidative stress induced by certain antioxidants.

Well known antioxidants-coumarins (7,8-dihydroxy-4-methyl coumarin-DHMC and 7,8-diacetoxy-4-methyl coumarin-DAMC) and flavonoids (quercetin-Q and quercetin penta-acetate-QPA) were investigated for their pro-oxidant effects in two human tumor cell lines. The breast carcinoma cell line (MDA-MB-468) was found to be more sensitive to treatment by the drugs-DAMC, Q and QPA at 10 microM than the glioma cell line (U-87MG), while DHMC was non toxic in both cell lines at this concentration. In MDA-MB-468 distinct growth inhibition was observed by 48 hr post treatment. Paradoxically, an increase in the formazan production was revealed by MTT assay at this time indicating an increase in the production of free radicals. An increase in the levels of reactive oxygen species (ROS) was also confirmed by DCFH-DA assay. In cells treated with DAMC, Q and QPA an increase in the percentage of cells with the hypodiploid DNA content was suggestive of apoptotic cell death. Taken together, these results suggest that an increase in oxidative stress caused by the pro-oxidant action of these drugs is responsible for cell death.

Buffalo plasma fibronectin: a physico-chemical study.

Plasma fibronectin (FN) of buffalo (Babulis babulis) was purified to apparent homogeneity, using gelatin-Sepharose and heparin-Sepharose affinity columns. It was found to have two subunits of molecular mass 246 kDa and 228 kDa, on SDS-gel. Its immunological cross-reactivity with anti-human plasma FN was confirmed by Western blotting. The amino acid composition was found to be similar to that of human and bovine plasma FNs. Buffalo plasma FN contained 2.23% neutral hexoses and 1.18% sialic acids. No titrable sulfhydryl group could be detected in the absence of denaturant. Reaction with DTNB indicated 3.4 sulfhydryl groups in the molecule, whereas BDC-OH titration gave a value of 3.8 -SH groups in buffalo plasma FN. Stoke's radius, intrinsic viscosity, diffusion coefficient and frictional ratio indicated that buffalo plasma FN did not have a compact globular conformation at physiological pH and ionic strength. Molecular dimensions (average length, 120 nm; molar mass to length ratio, 3950 nm(-1) and mean diameter, 2.4 nm) as revealed by rotary shadowing electron microscopy further supported the extended conformation of buffalo plasma FN. These results show that buffalo plasma FN has similar properties as that of human plasma FN.

Long-term stability of bronchial reactivity in guinea pigs.

Measurement of lung function and bronchial reactivity are widely used as outcome parameters to assess the efficacy of therapeutic interventions. In order to interpret the results correctly, it is necessary that the outcome parameters are themselves stable over time so that any significant changes measured may be attributed to the interventions. Specific airway conductance (SGaw) and airway reactivity to histamine are two commonly used parameters in animal models such as guinea pigs. Although short-term variability of these parameters has been investigated, there has been no study of long-term stability. In the present paper, SGaw and bronchial reactivity to histamine were measured in 111 conscious guinea pigs using a non-invasive, whole body plethysmograph. Baseline values of SGaw and ED35 histamine were measured and followed for eight weeks at weekly intervals. At baseline, mean SGaw in guinea pigs was 0.17 +/- 0.055 sec-1 cm H2O-1 and ED35 histamine ranged from 0.064 to more than 10 mg/ml. The distribution of ED35 histamine values was gaussian. We observed that the changes in SGaw and ED35 histamine recorded using this technique are highly reproducible over eight weeks. The reactivity varied by less than a doubling dose of histamine over any two consecutive weeks. Thus, the technique described in this paper is quick, easily learned, reproducible, independent of temperature-humidity artifact and highly suitable for studies of repeated measurements as in the study of dietary interventions and evaluation of effect of drugs.

Evaluation of risk factors for hearing impairment in at risk neonates by brainstem evoked response audiometry (BERA).

Thirteen (19.2%) of 68 at risk neonates in an intensive care nursery with one or more adverse perinatal clinical factors viz; prematurity (less than 37 wks), low birth weight (less than 2000 gm), hyperbilirubinemia requiring active intervention, birth anoxia, neonatal seizures, infections, aminoglycoside administration, and craniofacial malformations; were diagnosed to have hearing impairment (elevated auditory threshold) by BERA testing performed within the first six weeks of life at a mean conceptional (gestational age + age after birth) age of 40.2 +/- 0.6 wks. As against this, 20 healthy term neonates who were examined at a mean conceptional age of 40.4 +/- 0.8 weeks had a normal hearing threshold of 30 db nHL. Elevated auditory threshold was found more frequently in neonates with multiple clinical adverse factors than in those having single risk factor (6/13 Vs 7/55, p less than 0.001). On multiple logistic regression analysis, however, only 2 factors viz; hyperbilirubinemia at level exceeding indication for exchange transfusion and birth weight less than 1500 gm, were found to be significantly correlated with the hearing impairment in the affected neonates and in that order of importance. Prematurity, birth asphyxia, neonatal seizures, infections and aminoglycoside administration had no significant correlation with hearing impairment. Since most of the neonates admitted to the neonatal ICU have one or more identified adverse risk factors, their hearing screening by BERA at the time of discharge seems justified.

Hearing assessment by brainstem auditory evoked responses (BAER) in neonates at risk.

In the present study, brainstorm auditory evoked responses (BAER) were recorded in 68 at risk neonates discharged from the neonatal ICU of Safdarjung Hospital. The high risk group of 35 neonates included 13 neonates with multiple (3-4) risk factors and 22 neonates with single risk factors, viz., prematurity (less than 32 weeks) low birth weight (LBW) (less than 1500 g), hyperbilirubinemia requiring exchange transfusion, severe birth asphyxia, craniofacial malformations and sepsis with meningitis treated with amikacin for 3 weeks. The remaining 33 neonates were grouped in the low risk category who had only one of the following factors: prematurity (33-36 weeks)/LBW (1500-2000 g), hyperbilirubinemia requiring phototherapy, mild/moderate birth asphyxia, or sepsis treated with amikacin for 2 weeks. The test was performed at the mean conceptional age of 40.2 weeks (range 34-44 weeks) and involved determination of threshold of hearing as per presence of wave V. A normal response had wave V at 30 dB hearing level click stimulus at 50/sec from both ears or to 30 dB hearing level from one ear and 45 dB hearing level from the other ear. Thirteen neonates of the high risk group failed to produce a normal response (5 failed at 30 dB, 6 failed at 45 dB, and 2 failed at 75 dB hearing level). Forty six per cent of them had multiple high risk factors. All the low risk group neonates had normal threshold of 30 dB hearing level in the initial screening.(ABSTRACT TRUNCATED AT 250 WORDS)

Auditory brainstem response in neonates with hypoxic-ischemic-encephalopathy following perinatal asphyxia.

The technique of auditory brainstem evoked responses testing (ABR) was applied to twenty four new born infants with asphyxia complicated by hypoxic-ischemic-encephalopathy (HIE) in an attempt to study potential influence of HIE on hearing impairment. Twenty normal term neonates with no apparent neurological disorder, were also examined for comparison. Twenty two per cent (n = 5) of the patients with HIE showed some abnormality in the ABR pattern, the major one being a transient elevation in threshold of wave V (n = 4; 16.6%). ABR abnormalities, however, were found with greater frequency in neonates with Stage II HIE (75% vs 10%, p less than 0.001). Further ABR abnormalities were found in Stage II HIE only when duration of neurological abnormalities was greater than 5 days. There was no difference, however, between the ABR latencies of the asphyxiated and non-asphyxiated newborn infants (p greater than 0.05). One neonate (4%) with severe HIE, however, had persistent ABR abnormality in the form of bilateral absence of all waves in the later part of the ABR with preservation of wave I. This implied only cochlear functions and absence of any brainstem conduction. These results indicate that birth asphyxia complicated by HIE is a significant high risk factor for hearing impairment in the affected neonates. This justifies ABR testing of neonates with HIE (particularly Stage III), at the time of their discharge, as a screening procedure for early detection of permanent hearing loss.

Auditory brainstem responses (ABR) in neonates with hyperbilirubinemia.

The technique of ABR testing was applied to 25 infants with neonatal hyperbilirubinemia at levels exceeding that for exchange transfusion, in an attempt to study potential influence of bilirubin toxicity on the auditory brainstem pathway. The test was performed at a mean conceptional age of 40.4 +/- 0.6 weeks just after discharge. Twenty normal term neonates of comparable birth weights and conceptional ages, who had no hyperbilirubinemia, were also examined for comparison. Fifty six percent (n = 14) of the hyperbilirubinemic neonates had some abnormality in the ABR pattern, the major one being a transient increase in the threshold of wave V (7, fail-30; 5, fail-45). Wave V, however, was consistently present at 30 dBnHL click stimulus in all the normal neonates (pass-30; normal threshold). Further, mean ABR latencies (wave III, V) and 1-V interpeak latency (brainstem conduction time) were significantly prolonged in jaundiced neonates as compared with controls (P less than 0.01). ABR changes were strongly correlated with the serum bilirubin levels (P less than 0.001). On follow up retesting at 3 months, however, all infants were found to have normal ABR latencies and threshold. Neonatal jaundice was associated with significant transient aberrations of ABR, suggestive of a transient toxic brainstem encephalopathy.