Early radiological outcomes of a fully porous bridging collar in lower-limb endoprosthetic reconstructions: a case-matched retrospective series to assess osseointegration.

BACKGROUND: Limb-salvage surgery involving the utilization of endoprosthetic replacements is commonly employed following segmental bone resection for primary and secondary bone tumors. This study aimed to evaluate whether a fully porous bridging collar promotes early osseous integration in endoprosthetic replacements. METHODS: We undertook a retrospective review of all lower-limb endoprostheses utilizing a fully porous endosteal bridging collar design. We matched this cohort with a conventional extra-osteal non-porous fully hydroxyapatite-coated grooved collar cohort according to surgical indication, implant type, resection length, age, and follow-up time. At 6, 12, and 24 months post-implantation, radiographs were assessed for the number of cortices with or without osseointegration on orthogonal radiographs. Each radiograph was scored on a scale of -4 to + 4 for the number of cortices bridging the ongrowth between the bone and the collar of the prosthesis. Implant survival was estimated using the Kaplan-Meier method, and the mean number of osseointegrated cortices at each time point between the collar designs was compared using a paired t-test. RESULTS: Ninety patients were retrospectively identified and analyzed. After exclusion, 40 patients with porous bridging collars matched with 40 patients with conventional extra-osteal non-porous collars were included in the study (n = 80). The mean age was 63.4 years (range 16-91 years); there were 37 males and 43 females. The groups showed no difference in implant survival (P = 0.54). The mean number of cortices with radiographic ongrowth for the porous bridging collar and non-porous collar groups was 2.1 and 0.3, respectively, at 6-month (P < 0.0001), 2.4 and 0.5, respectively, at 12-month (P = 0.044), and 3.2 and -0.2, respectively, at 24-month (P = 0.18) radiological follow-up. CONCLUSION: These findings indicate that fully porous bridging collars increased the number of cortices, with evidence of bone ongrowth between 6 and 24 months post-implantation. By contrast, extra-osteal collars exhibited reduced evidence of ongrowth between 6 and 24 months post-implantation. In the medium term, the use of a fully porous bridging collar may translate to a reduced incidence of aseptic loosening.

The importance of low-dose CT screening to identify emphysema in asymptomatic participants with and without a prior diagnosis of COPD.

PURPOSE: Chronic Obstructive Pulmonary Disease (COPD) includes chronic bronchitis, small airways disease, and emphysema. Diagnosis of COPD requires spirometric evidence and may be normal even when small airways disease or emphysema is present. Emphysema increases the risk of exacerbations, and is associated with all-cause mortality and increased risk of lung cancer. We evaluated the prevalence of emphysema in participants with and without a prior history of COPD. METHODS: We reviewed a prospective cohort of 52,726 subjects who underwent baseline low dose CT screening for lung cancer from 2003 to 2016 in the International Early Lung Cancer Action Program. RESULTS: Of 52,726 participants, 23.8%(12,542) had CT evidence of emphysema. Of these 12,542 participants with emphysema, 76.5%(9595/12,542) had no prior COPD diagnosis even though 23.6% (2258/9595) had moderate or severe emphysema. Among 12,542 participants, significant predictors of no prior COPD diagnosis were: male (OR = 1.47, p < 0.0001), younger age (ORage10 = 0.72, p < 0.0001), lower pack-years of smoking (OR10pack-years = 0.90, p < 0.0001), completed college or higher (OR = 1.54, p < 0.0001), no family history of lung cancer (OR = 1.12, p = 0.04), no self-reported cardiac disease (OR = 0.76, p = 0.0003) or hypertension (OR = 0.74, p < 0.0001). The severity of emphysema was significantly lower among the 9595 participants with no prior COPD diagnosis, the OR for moderate emphysema was ORmoderate = 0.58(p = 0.0007) and for severe emphysema, it was ORsevere = 0.23(p < 0.0001). CONCLUSION: Emphysema was identified in 23.8% participants undergoing LDCT and was unsuspected in 76.5%. LDCT provides an opportunity to identify emphysema, and recommend smoking cessation.

Synthesis, biological evaluation and molecular dynamic simulations of novel Benzofuran-tetrazole derivatives as potential agents against Alzheimer's disease.

A series of novel Benzofuran-tetrazole derivatives were successfully synthesised by integrating multicomponent Ugi-azide reaction with the molecular hybridization approach. Interestingly, a number of synthesized derivatives (5c, 5d, 5i, 5l, 5q and 5s) exhibited significant reduction of aggregation of "human" amyloid beta peptide, expressing on transgenic Caenorhabditis elegans (C. elegans) strain CL4176. Further, in silico docking results have evidenced the exquisite interaction of active compounds with the help of TcAChE-E2020 complex. These findings underscore the potential of these hybrids as lead molecules against Alzheimers's disease.

Association of core needle biopsy tract resection with local recurrence in extremity soft tissue sarcoma.

OBJECTIVE: Due to minimal tissue violation in percutaneous core needle biopsy (CNB), in contrast to open biopsy, the risk of tumor seeding and subsequent local recurrence (LR) along the biopsy tract remains unclear in extremity soft tissue sarcoma (STS). This study sought to examine the association of CNB tract resection on LR in a large STS institutional database. MATERIALS AND METHODS: After a retrospective review of the 116 patients who underwent CNB prior to surgery for previously untreated non-metastatic extremity STS, 36 patients who did not have CNB tracts resected (CNB-NR) were matched with 36 who had CNB tracts resected (CNB-R) for the factors that are known to affect LR. RESULTS: Two patients (6%) developed LR in the CNB-R group, whereas three patients (8%) developed LR in the CNB-NR group (P = 0.643). On Kaplan-Meier analysis, there was no significant difference in LR-free survival between the two groups (94.3% ± 3.9 for the CNB-R group vs. 93.8% ± 4.3 for the CNB-NR group, P = 0.747). CONCLUSION: Our data suggest any influence of a CNB tract resection on LR, within the limitations of this study, is likely to be of minor clinical importance in extremity STS. Although it would be prudent to resect the CNB tract in most cases, not resecting the CNB tract is a feasible option if identification or removal of the CNB tract proves difficult.

Cross reactive molecules of human lymphatic filaria Brugia malayi inhibit Leishmania donovani infection in hamsters.

Coinfections are common in natural populations and the outcome of their interactions depends on the immune responses of the host elicited by the parasites. Earlier we showed that immunization with BmAFII (Sephadex G-200 eluted) fraction of human lymphatic filaria Brugia malayi inhibited progression of Leishmania donovani infection in golden hamsters. In the present study we identified cross reactive molecules of B. malayi, and investigated their effect on L. donovani infection and associated immune responses in the host. The sequence alignment and sharing of linear T- and B-cell epitopes in protein molecules of B. malayi and L. donovani counterparts were studied in silico. Hamsters were immunized with robustly cross reactive SDS-PAGE resolved fractions F6 (54.2-67.8kDa) and F9 (41.3-45.0kDa) of B. malayi and subsequently inoculated with amastigotes of L. donovani intracardially. F6 inhibited (∼72%) L. donovani infection and upregulated Th1 cytokine expression, lymphoproliferation, IgG2, IgG2/3 levels and NO production, and downregulated Th2 cytokine expression. Sequences in HSP60 and EF-2 of F6 and L. donovani counterparts were conserved and B- and T-cell epitopes in the proteins shared antigenic regions. In conclusion, leishmania-cross reactive molecules of filarial parasite considerably inhibited leishmanial infection via Th1-mediated immune responses and NO production. Common B- and T-cell epitope regions in HSP60 and EF-2 of the parasites might have contributed to the inhibitory effect on the L. donovani infection. Thus, leishmania-cross reactive filarial parasite molecules may help in designing prophylactic(s) against L. donovani.

Intra-operative cell salvage in cardiac surgery may increase platelet transfusion requirements: a cohort study.

BACKGROUND AND OBJECTIVES: The cell saver (CS) has been widely utilized in cardiac surgery to reduce red blood cell (RBC) transfusion. We aim at examining its effect on the rate of allogeneic transfusion, morbidity and mortality in our population. MATERIALS AND METHODS: Retrospective review of all patients operated at the Sultan Qaboos University Hospital between 2008 and 2013 was performed. Patients' demographics, comorbidities and surgical details were retrieved. Study end-points included blood transfusion, infection, renal failure and mortality. Baseline characteristics of both groups were compared and differences were adjusted for in the multivariable logistic regression. RESULTS: A total of 673 patients were included (CS = 395, non-CS = 278). Baseline characteristics were similar except for systemic hypertension, congestive heart failure and use of cardiopulmonary bypass. The CS group had higher transfusion rates of platelets (CS 36% vs. non-CS 18%; P < 0·001) and plasma (CS 31% vs. non-CS 19%; P < 0·001). After adjusting for baseline differences, CS use increased the odds of receiving platelet transfusion (odds ratio (OR) 3·2; P < 0·001) but not of plasma transfusion (OR 1·6; P = 0·087). There was no difference in the rate of RBC transfusion (CS 45% vs. non-CS 40%; P = 0·212), renal failure (CS 11% vs. non-CS 6%; P = 0·139), infection (CS 16% vs. non-CS 13%; P = 0·434) and mortality (CS 5% vs. non-CS 2%; P = 0·146). CONCLUSION: The CS use increases platelet requirements and has no impact on the rate of RBC transfusion in our population. These findings warrant caution with generalized use and require larger studies to confirm its results.

Disorganized muscle protein-1 (DIM-1) of filarial parasite Brugia malayi: cDNA cloning, expression, purification, structural modeling and its potential as vaccine candidate for human filarial infection.

We have recently identified disorganized muscle protein-1 (DIM-1) in one of the proinflammatory fractions of the human filaria Brugia malayi adult worm. The present study was undertaken to characterize B. malayi DIM-1 (DIM-1bm) and explore its vaccine potential. In this study we cloned and expressed the DIM-1bm gene, investigated its sequence homology with other nematodes, constructed in silico structural model, purified the recombinant DIM-1bm (rDIM-1bm) protein, and studied the effect of immunization with rDIM-1bm on the establishment of B. malayi infection in Mastomys coucha. DIM-1bm showed similarity with DIM-1 of Caenorhabditis elegans, Ascaris suum and Loa loa. Structural modeling revealed three immunoglobulin domains in DIM-1bm indicating that it is a member of immunoglobulin superfamily (IgSF) and 'blastn' results showed that DIM-1bm coding sequence (CDS) have almost no homology with human and mouse nucleotide sequences. Immunization with rDIM-1bm partially protected M. coucha against establishment of infection as inferred by a low recovery of microfilariae (37-64%) and parasite burden (∼50%). The enhanced activity of macrophages, and IFN-γ and NO responses, and elevated levels of specific IgG, IgG1, IgG2a and IgG2b correlated with parasitological findings. This is the first report on cloning, expression, structural modeling and purification of rDIM-1bm and its ability to partially prevent establishment of B. malayi infection. DIM-1bm's almost complete lack of homology with the human counterpart makes it an attractive protein for exploring its vaccine potential.

Study of TLR4 and IL-8 gene polymorphisms in H.pylori-induced inflammation in gastric cancer in an ethnic Kashmiri population.

BACKGROUND: TLRs play an essential role in the initial handling of H. pylori and determine the clinical outcomes that range from simple asymptomatic gastritis to peptic ulcer disease and gastric cancer. Asp299Gly and Thr399Ile polymorphisms in TLR4 have been associated with a variety of inflammatory and infectious conditions including gastric cancer. The T-251A polymorphism in the promoter region of IL-8 gene has been found to be associated with changing the in vitro levels of IL-8 production. IL-8 exhibits angiogenic activity and is responsible for tumor-associated angiogenesis in several cancers. MATERIALS AND METHODS: 130 gastric cancer patients and 200 healthy controls were included in this study. DNA extraction was followed by PCR detection of H. pylori infection, PCR-RFLP for the TLR 4 polymorphism and PCR-CTPP for IL-8 gene polymorphism. RESULTS: The adjusted OR for gastric cancer risk was 1.15 (95% CI, 0.8357-1.3463); 1.39 (0.6964-2.781) and 1.43 (0.954-2.1515) for Asp299Gly, Thr399Ile and IL-8 T_251A respectively. Odds Ratio analysis showed CT genotype and AT and AA genotypes as risk factors for the development of gastric cancer. We found the Asp299Gly polymorphism carrier to be significantly associated (p value 0.03)with the development of tumours in the distal part of the stomach and Thr399Ile polymorphism to be significantly associated(p value 0.008) with the development of well-differentiated gastric adenocarcinoma.The IL-8 T-251A polymorphism was not found to be associated with any of the clinicopathological characteristics. DISCUSSION: No correlation was found between the appearance of disease and HP infection or the presence of TLR4 and IL-8 gene polymorphisms and HP infection.

Heat shock protein 60 of filarial parasite Brugia malayi: cDNA cloning, expression, purification and in silico modeling and analysis of its ATP binding site.

We report here cloning and expression of full length mitochondrial HSP60 gene of Brugia malayi adult worm (mtHSP60bm), purification of the gene product by affinity chromatography, its in silico 3D structure and the sequence homology of the protein with Escherichia coli GroEL/ES and human HSP60. The ATP binding pocket of human HSP60 and mtHSP60bm were analyzed and compared using in silico models. The distribution of HSP60 in different life-stages of the parasite was determined using antibodies raised against recombinant mtHSP60bm (rmtHSP60bm). mtHSP60bm was present in all life-stages of the parasite except third stage infective larvae, in which it could be induced by heat-shock, and showed high degree of homology with E. coli GroEL/ES. The ATP binding pocket of HSP60 in humans, E. coli and B. malayi were also found structurally conserved. This similarity between human and mtHSP60bm might be useful in understanding the host-parasite interactions. This is the first ever report on distribution, cloning, sequence homology and ATP binding site of mtHSP60bm.

Genetic polymorphism of the glutathione-S-transferase P1 gene (GSTP1) and susceptibility to prostate cancer in the Kashmiri population.

Glutathione-S-transferase P1 (GSTP1) is a critical enzyme of the phase II detoxification pathway. One of the common functional polymorphisms of GSTP1 is A→G at nucleotide 313, which results in an amino acid substitution (Ile105Val) at the substrate binding site of GSTP1 and reduces catalytic activity of GSTP1. To investigate the GSTP1 Ile105Val genotype frequency in prostate cancer cases in the Kashmiri population, we designed a case-control study, in which 50 prostate cancer cases and 45 benign prostate hyperplasia cases were studied for GSTP1 Ile105Val polymorphism, compared to 80 controls taken from the general population, employing the PCR-RFLP technique. We found the frequency of the three different genotypes of GSTP1 Ile105Val in our ethnic Kashmir population, i.e., Ile/Ile, Ile/Val and Val/Val, to be 52.4, 33.3 and 14.3% among prostate cancer cases, 48.5, 37.5 and 14% among benign prostate hyperplasia cases and 73.8, 21.3 and 5% in the control population, respectively. There was a significant association between the GSTP1 Ile/Val genotype and the advanced age group among the cases. We conclude that GSTP1 Ile/Val polymorphism is involved in the risk of prostate cancer development in our population.

Risk of colorectal cancer associated with the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in the Kashmiri population.

Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA synthesis, DNA repair and DNA methylation. The two common functional polymorphisms of MTHFR, 677 C→T and 1298 A→C, have been shown to impact various diseases, including cancer. The 677 C→T polymorphism has been widely investigated in different cancers and has been implicated as a risk factor for the development of various cancers. We investigated MTHFR C677T genotype frequency in colorectal cancer cases in the Kashmiri population and correlated this information with the known clinicopathological characters of colorectal cancer, in a case-control study. Eighty-six colorectal cancer cases were studied for MTHFR C677T polymorphism, compared to 160 controls taken from the general population, employing the PCR-RFLP technique. We found the frequency of the three different genotypes of MTHFR in our ethnic Kashmir population, i.e., CC, CT and TT, to be 68.6, 20.9 and 10.4% among colorectal cancer cases and 75.6, 16.9 and 7.5% among the general control population, respectively. There was a significant association between the MTHFR TT genotype and colorectal cancer in the higher age group. We conclude that the MTHFR C677T polymorphism slightly increases the risk for colorectal cancer development in our ethnic Kashmir population.

Chronic calcific pancreatitis: combination ERCP and extracorporeal shock wave lithotripsy for pancreatic duct stones.

BACKGROUND: Chronic pancreatitis is commonly associated with debilitating abdominal pain, in part due to pancreatic duct obstruction. Pancreatic stones are often impossible to extract from the duct with endoscopic retrograde cholangiopancreatography alone. Extracorporeal shock wave lithotripsy (ESWL) is commonly used for fragmentation of obstructing nephrolithiasis and has demonstrated effectiveness in management of pancreatic stones. Our aim was to examine the outcomes of the first 30 patients with symptomatic pancreatic stones treated with a combination of ESWL and endoscopic therapies. METHODS: Patients with symptomatic chronic calcific pancreatitis referred for ESWL (2005-2009) were included. Technical success of ESWL was defined as a) stone fragmentation sufficient to allow extraction of main duct stones at ERCP or b) absence of the targeted main pancreatic duct stones on follow-up radiography. Clinical success of ESWL was defined by Patient Global Impression of Improvement (PGII) score of at least slightly improved. RESULTS: Thirty patients underwent ESWL. One patient was excluded due to adenocarcinoma. Technical success was achieved in 17/29 (58.6%) patients. 25 (86.2%) patients were available for follow-up (median 35 months, range 3-52 months). Fifteen of twenty-five (60%) patients experienced clinical improvement (10 patients very much improved), but there was no significant reduction in the proportion taking narcotics (50% before vs. 44.4% after ESWL). Pancreatic surgery has been avoided to date in 16 (64%) of the 25 patients. CONCLUSIONS: A multidisciplinary approach, combining ERCP and ESWL, to painful obstructing pancreatic duct stones provided symptomatic improvement and allowed pancreatic surgery to be avoided in the majority of patients.

TP53 Pro47Ser and Arg72Pro polymorphisms and colorectal cancer predisposition in an ethnic Kashmiri population.

Two TP53 gene polymorphisms at codon 47 (TP53 Pro47Ser) and at codon 72 (TP53 Arg72Pro) have been associated with susceptibility to various cancers. We carried out a case-control study and examined the genotype distribution of TP53 Pro47Ser and Arg72Pro single nucleotide polymorphisms (SNPs), using a PCR-RFLP approach, to determine if these two SNPs are risk factors for colorectal cancer (CRC) development and to look for a possible correlation of these two SNPs with clinicopathological variables of CRC. We investigated the genotype distribution of these SNPs in 86 CRC cases in comparison with 160 healthy subjects in an ethnic Kashmiri population. TP53 Arg72Pro SNP genotype frequencies differed significantly (P = 0.000001) between the groups; the frequency of the Pro/Pro mutant was almost 20% in the general population. We also found significant association of the Pro/Pro mutant with tumor location, nodal status/higher tumor grade and bleeding per rectum/constipation. We conclude that Arg72Pro SNP is associated with susceptibility to developing CRC in this ethnic Kashmiri population.

3D-QSAR studies on quinazoline antifolate thymidylate synthase inhibitors by CoMFA and CoMSIA models.

Thymidylate synthase (TS) is a crucial enzyme for DNA biosynthesis and many nonclassical lipophilic antifolates targeting this enzyme are quite efficient and encouraging as antitumor drugs. Herein, we report some 3D-QSAR analyses using CoMFA and CoMSIA on quinozoline antifolates in order to have a better understanding of the mechanism of action and structure-activity relationship of these compounds. By applying leave-one-out (LOO) cross-validation study, we obtained cross-validated q(2) value of 0.573 for CoMFA and 0.445 for CoMSIA, while the non-cross-validated r(2) values for them were found to be 0.935 and 0.893, respectively. The models were graphically interpreted using CoMFA and CoMSIA contour plots. The results obtained from this study could be used for rational design of potent inhibitors against thymidylate synthase.

Mutation pattern of K-ras gene in colorectal cancer patients of Kashmir: a report.

BACKGROUND AND AIM: Colorectal cancer (CRC) is one of the leading malignancies worldwide. CRC has been reported to show geographical variation in its incidence, even within areas of ethnic homogeneity. The aim of this study is to identify K-ras gene mutations in CRC patients among the Kashmiri population, and to assess whether they are linked with the clinicopathological parameters. MATERIALS AND METHODS: Paired tumor and normal tissue samples were collected from a consecutive series of 53 patients undergoing resective surgery for CRC. In addition blood was also collected from all the cases for ruling out germline mutation. RESULTS: Colorectal patients, 22.64% (12 of 53), presented with mutations in K-ras constituting 13 missense mutations out of which 11 were G-->A transition, one G-->C transversion, and one G-->T transversion. 61.5% percent of the mutations occurred in codon 12 and 38.5% in codon 13. One tumor contained missense mutations in both codons. K-ras mutations were significantly associated with advanced Dukes' stage (P < 0.05) and positive lymph node status (P < 0.05). Moreover Codon 12 K-ras mutations were associated with mucinous histotype (P < 0.05). Comparison of the mutation profile with other high-risk areas reflected both mucinous histotype differences and similarities indicating coexposure to a unique set of risk factors. CONCLUSION: Mutation of the K-ras gene is one of the commonest genetic changes in the development of human CRC, but it occurs in a rather low frequency in Kashmiri population.

Induction of apoptosis in human leukemia cells by black tea and its polyphenol theaflavin.

Treatment of human leukemic cell lines HL-60 and K-562 with extracts of green and black tea and their polyphenols epigallocatechin gallate and theaflavins, respectively, showed a dose dependent inhibition of growth as a result of cytotoxicity and suppression of cell proliferation. Based on the IC50 values obtained from cytotoxicity data it was clearly evident that black tea was as efficient as green tea. Analysis of polyphenol contents of tea extracts revealed that not only epigallocatechin gallate, which is a predominant polyphenol of green tea, but also theaflavin that is abundantly present in black tea affords significant chemotherapeutic action by imparting cytotoxicity to human leukemic cells. Electrophoretic analysis of fragmented DNA from treated cells displayed characteristic ladder pattern. Flow cytometric analysis revealed the dose dependent increase in sub-G1 peak. These criteria confirmed that cytotoxic activity of green and black tea was due to induction of apoptosis. Such induction was found to be mediated through activation of caspases 3 and 8, particularly caspase 3 and by altering apoptosis related genes as evident by down-regulation of Bcl-2 and up-regulation of Bax proteins.

Determination of the essentiality of the eight cysteine residues of the NrtA protein for high-affinity nitrate transport and the generation of a functional cysteine-less transporter.

All eight cysteine residues, C90, C94, C143, C147, C219, C325, C367, and C431, present in transmembrane domains of the Aspergillus nidulans NrtA nitrate transporter protein were altered individually by site-specific mutagenesis. The results indicate that six residues, C90, C147, C219, C325, C367, and C431, are not required for nitrate transport. Although alterations of C94 and C143 are less well tolerated, these residues are not mandatory and their possible role is discussed. A series of constructs, all completely devoid of cysteine residues, was generated to permit future cysteine-scanning mutagenesis. The optimum cysteine-less combination was identified as C90A, C94A, C143A, C147T, C219S, C325S, C367S, and C431S. This mutant combination yielded transformant strains with up to 40% of wild-type nitrate transport activity. Furthermore, the K(m) value and the level of protein expression were found to be similar to those of the wild-type. This cysteine-less vector should allow us to investigate in detail potentially interesting NrtA amino acids (e.g. identified from homology comparisons) which may be involved in transport, by altering these singly to cysteine and studying such residues by thiol chemistry.

Visual inspection with acetic acid and cytology in the early detection of cervical neoplasia in Kolkata, India.

Visual inspection of the cervix after application of 3-5% acetic acid (VIA) is a potential alternative to cytology for screening in low-resource countries. The present study evaluated the performance of VIA, magnified visual inspection after application of acetic acid (VIAM), and cytology in the detection of high-grade cervical cancer precursor lesions in Kolkata (Calcutta) and suburbs in eastern India. Trained health workers with college education concurrently screened 5881 women aged 30-64 years with VIA, VIAM, and conventional cervical cytology. Detection of well-defined, opaque acetowhite lesions close to the squamocolumnar junction; well-defined, circumorificial acetowhite lesions; or dense acetowhitening of ulceroproliferative growth on the cervix constituted a positive VIA or VIAM. Cytology was considered positive if reported as mild dysplasia or worse lesions. All screened women (N = 5881) were evaluated by colposcopy, and biopsies were directed in those with colposcopic abnormalities (N = 1052, 17.9%). The final diagnosis was based on histology (if biopsies had been taken) or colposcopic findings, which allowed direct estimation of sensitivity, specificity, and predictive values. Moderate or severe dysplasia or carcinoma in situ (CIN 2-3 disease) was considered as true positive disease for the calculation of sensitivity, specificity, and predictive values of screening tests. 18.7%, 17.7% and 8.2% of the women tested positive for VIA, VIAM, and cytology. One hundred twenty two women had a final diagnosis of CIN 2-3 lesions. The sensitivities of VIA and VIAM to detect CIN 2-3 lesions were 55.7% and 60.7%, respectively; the specificities were 82.1% and 83.2%, respectively. The sensitivity and specificity of cytology were 29.5% and 92.3%, respectively. All the tests were associated with negative predictive values above 98%. VIA and VIAM had significantly higher sensitivity than cytology in our study; the specificity of cytology was higher than that of VIA and VIAM.

Modulation of arsenic induced cytotoxicity by tea.

Arsenic, a naturally ocurring chemical element, is considered hazardous to human health. Inorganic arsenic compounds were found to induce cytotoxicity in Chinese hamster V-79 cells in culture. The arsenite form was more toxic than arsenate. Extracts of green and two varieties of black tea, as well as their principal polyphenols, (-)-epigallocatechingallate and theaflavin, efficiently counteracted the cytotoxic effects of arsenic compounds. On the basis of the amount of tea extract that afforded 50% protection to the cells from arsenic induced cytotoxicity, black tea was found to be as effective as green tea. The protective effect was attributable to the contents of not only (-)-epigallocatechingallate but also of theaflavin, the latter being a predominant polyphenol present in black tea.

Augmented TNF-alpha and IL-10 production by primed human monocytes following interaction with oxidatively modified autologous erythrocytes.

The presence of dysfunctional/damaged red blood cells (RBCs) has been associated with adverse clinical effects during the inflammatory response. The aim of this study was to elucidate whether oxidatively modified, autologous RBCs modulate monocyte cytokine responses in humans. Monocyte tumor necrosis factor alpha (TNF-alpha) and IL-10 production was measured in whole blood from healthy volunteers using ELISA and flow cytometry. Oxidatively modified RBCs (15 mM phenylhydrazine, 1 h, OX-RBC) or vehicle-treated RBCs (VT-RBC) opsonized by autologous serum were administered alone or in combination with one of three priming agents: E. coli lipopolysaccharide (LPS, 0.2 ng/ml), zymosan A (1 mg/ml), or phorbol 12-myristate 13-acetate (PMA, 50 ng/ml). OX-RBC or VT-RBC alone did not result in the release of TNF-alpha or IL-10. LPS, zymosan, and PMA caused marked and dose-dependent increases in TNF-alpha and IL-10 production. Addition of OX-RBC augmented the LPS-, zymosan-, and PMA-induced TNF-alpha release by approximately 100%. OX-RBC augmented LPS- and zymosan-induced IL-10 release by 400-600%. Flow cytometry analyses showed that monocytes were responsible for TNF-alpha and IL-10 production in whole blood. The presence of OX-RBC alone increased the complexity of CD14+ monocytes but caused no cytokine production. LPS alone induced cytokine production without altering cell complexity. After the combined (OX-RBC+LPS) treatment, monocytes of high complexity were responsible for TNF-alpha production. The presence of mannose or galactose (at 10-50 mM) did not alter the observed augmentation of cytokine production by OX-RBC, suggesting that lectin receptors are not involved in the response. These studies indicate that the interaction between damaged autologous erythrocytes and monocytes has a major impact on the cytokine responses in humans. An augmented cytokine production by the mononuclear phagocyte system may adversely affect the clinical course of injury and infections especially in genetic or acquired RBC diseases or after transfusions.