Bacteroidales recruit IL-6-producing intraepithelial lymphocytes in the colon to promote barrier integrity.

Interactions between the microbiota and distal gut are important for the maintenance of a healthy intestinal barrier; dysbiosis of intestinal microbial communities has emerged as a likely contributor to diseases that arise at the level of the mucosa. Intraepithelial lymphocytes (IELs) are positioned within the epithelial barrier, and in the small intestine they function to maintain epithelial homeostasis. We hypothesized that colon IELs promote epithelial barrier function through the expression of cytokines in response to interactions with commensal bacteria. Profiling of bacterial 16S ribosomal RNA revealed that candidate bacteria in the order Bacteroidales are sufficient to promote IEL presence in the colon that in turn produce interleukin-6 (IL-6) in a MyD88 (myeloid differentiation primary response 88)-dependent manner. IEL-derived IL-6 is functionally important in the maintenance of the epithelial barrier as IL-6-/- mice were noted to have increased paracellular permeability, decreased claudin-1 expression, and a thinner mucus gel layer, all of which were reversed by transfer of IL-6+/+ IELs, leading to protection of mice in response to Citrobacter rodentium infection. Therefore, we conclude that microbiota provide a homeostatic role for epithelial barrier function through regulation of IEL-derived IL-6.

Post-Transcriptional Regulation of Hepatic DDAH1 with TNF Blockade Leads to Improved eNOS Function and Reduced Portal Pressure In Cirrhotic Rats.

Portal hypertension (PH) is a major cause of morbidity and mortality in chronic liver disease. Infection and inflammation play a role in potentiating PH and pro-inflammatory cytokines, including TNF, are associated with severity of PH. In this study, cirrhotic bile duct ligated (BDL) rats with PH were treated with Infliximab (IFX, a monoclonal antibody against TNF) and its impact on modulation of vascular tone was assessed. BDL rats had increased TNF and NFkB compared to sham operated rats, and their reduction by IFX was associated with a reduction in portal pressure. IFX treatment also reduced hepatic oxidative stress, and biochemical markers of hepatic inflammation and injury. IFX treatment was associated with an improvement in eNOS activity and increased L-arginine/ADMA ratio and DDAH1 expression. In vitro analysis of HepG2 hepatocytes showed that DDAH1 protein expression is reduced by oxidative stress, and this is in part mediated by post-transcriptional regulation by the 3'UTR. This study supports a role for the DDAH1/ADMA axis on the effect of inflammation and oxidative stress in PH and provides insight for new therapies.

Ten-year alcohol consumption typologies and trajectories of C-reactive protein, interleukin-6 and interleukin-1 receptor antagonist over the following 12 years: a prospective cohort study.

BACKGROUND: Moderate alcohol consumption is thought to confer cardiometabolic protective effects. Inflammatory pathways are hypothesized to partly underlie this association. OBJECTIVES: The aim of this study was to examine the association between typologies of alcohol consumption and markers of inflammation, and their rate of change over time. METHODS: Data were collected from 8209 participants [69% men; mean age, 50 years (SD 6.1)] of the British Whitehall II study. Alcohol consumption typologies were defined using up to three measures during an approximately 10-year period spanning from 1985 to 1994 as (i) stable nondrinkers, (ii) stable moderate drinkers (referent), (iii) stable heavy drinkers, (iv) nonstable drinkers and (v) former drinkers. C-reactive protein (CRP), interleukin (IL)-6 and IL-1 receptor antagonist (IL-1 RA) were measured up to three times in the following 12 years. RESULTS: Stable moderate drinkers had lower levels of CRP than stable nondrinkers, stable heavy drinkers, former drinkers and nonstable drinkers, but there were no differences in the rate of change in CRP over time between groups. Stable nondrinkers had higher levels of IL-6 as did stable heavy drinkers; rates of change in IL-6 over time were also increased in the latter group. Stable nondrinkers also had higher levels of IL-1 RA. These associations were robust to adjustment for confounding factors. CONCLUSION: Our novel investigation of 10-year drinking typologies shows that stable moderate alcohol consumption is associated with a long-term inflammatory marker profile that is consistent with conferring a reduced risk of developing coronary heart disease.

SWI/SNF chromatin remodeling enzymes in melanocyte differentiation and melanoma.

Epidermal melanocytes are pigment-producing cells derived from the neural crest that protects skin from the damaging effects of solar radiation. Malignant melanoma, a highly aggressive cancer, arises from melanocytes. SWI/SNF enzymes are multiprotein complexes that remodel chromatin structure and have extensive roles in cellular differentiation. Components of the complex have been found to be mutated or lost in several human cancers. This review focuses on studies that implicate SWI/SNF enzymes in melanocyte differentiation and in melanoma.

Feasibility study of FDG PET/CT-derived primary tumour glycolysis as a prognostic indicator of survival in patients with non-small-cell lung cancer.

AIM: To assess the feasibility and prognostic value of measuring total lesion glycolysis of the primary tumour (TLG(primary)) using combined 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography/computed tomography (PET/CT) in patients with proven or suspected non-small-cell lung cancer (NSCLC) in the routine diagnostic setting. MATERIALS AND METHODS: At the All wales Research and Diagnostic Positron Emission Tomography Centre in Cardiff (PETIC), in the calendar year 2011, 288 consecutive patients were identified with a single pulmonary mass in whom NSCLC was confirmed or clinically diagnosed following multidisciplinary team review. In a retrospective analysis, for each patient the PET-derived volume of the primary tumour and SUVMEAN was calculated using adaptive thresholds of 40% and 50% of the SUVMAX of the primary tumour. The TLG(primary) (calculated by volume x SUVMEAN) was calculated at these two thresholds and was used to predict survival in a multivariate analysis with TNM (tumour, node, metastasis) stage, age, sex, and SUV(MAX). The primary endpoint was overall survival over a minimum follow-up of at least 7 months. RESULTS: In virtually every case, the primary tumour could be measured using the automated software with minimal use of manual adjustments. In multivariate analysis, TNM clinical stage, log(TLG(primary)) and sex were independent predictors of overall survival. CONCLUSION: Measurements of primary tumour total lesion glycolysis are simple to perform and provide additional prognostic information over and above that provided by TNM staging.

Utility of intraoperative angiography during subaxial foramen transversarium decompression for bow hunter's syndrome.

Bow hunter's syndrome is an uncommon cause of vertebrobasilar insufficiency resulting from rotational compression of the extracranial vertebral artery. While positional compression of any portion of the extracranial vertebral artery has been reported to result in bow hunter's syndrome, the most common site of compression is the V2 segment as it passes through the foramen transversarium of the subaxial cervical spine. A 43-year-old woman presented with increasingly frequent pre-syncopal and syncopal episodes upon leftward head rotation. Pre-operative angiographic studies with the neck rotated to the left demonstrated occlusion of the left vertebral artery by a C4-5 osteophyte arising from the C4 uncinate process. The patient underwent microsurgical decompression of the vertebral artery at C4-5 through a standard anterior transcervical retropharyngeal approach. Selective vertebral artery intraoperative angiography performed with the head passively rotated to the left before and after left vertebral artery decompression showed marked improvement in the luminal diameter and blood flow. The patient's symptoms resolved post-operatively. This case illustrates the second instance of intraoperative angiography used to confirm adequate vertebral artery decompression for bow hunter's syndrome. Intraoperative angiography can be safely used to decrease the extent of vertebral artery decompression in order to minimize the risk of operative complications.

Prevalence of extended spectrum beta-lactamases producing clinical isolates from patients of urinary tract infection in a tertiary care hospital in Delhi.

A total of 250 urinary isolates (188 Escherichia coli and 62 Klebsiella pneumoniae) were studied for ESBL production by double disc approximation test and disc diffusion confirmatory test (NCCLS). ESBL production was found to be 56% in E. coli and 52% in K. pneumoniae. The double disc approximation test showed false ESBL production in five (2.6%) isolates of E. coli and one (1.6%) K. pneumoniae. The susceptibility of ESBL producers to imipenem, amikacin, nitrofurantion was found to be 100%, 86% and 84% respectively. A high degree of co-resistance to co- trimaxazole and norfloxacin was found in strains of ESBL producers. Seventy five per cent of ESBL producers detected were from hospitalized patients admitted in ICU or undergoing surgery.

Intraoperative glove perforation--single versus double gloving in protection against skin contamination.

Surgeons have the highest risk of contact with patients' blood and body fluids, and breaches in gloving material may expose operating room staff to risk of infections. This prospective randomised study was done to assess the effectiveness of the practice of double gloving compared with single gloving in decreasing finger contamination during surgery. In 66 consecutive surgical procedures studied, preoperative skin abrasions were detected on the hands of 17.4% of the surgeons. In the double gloving pattern, 32 glove perforations were observed, of which 22 were in the outer glove and 10 in the inner glove. Only four outer glove perforations had matching inner glove perforations, thus indicating that in 82% of cases when the outer glove is perforated the inner glove will protect the surgeon's hand from contamination. The presence of visible skin contamination was also higher in perforation with the single gloving pattern (42.1%) than with the double gloving pattern (22.7%). An overwhelming majority of glove perforations (83.3%) went unnoticed. Double gloving was accepted by the majority of surgeons, especially with repeated use. It is recommended that double gloves are used routinely in all surgical procedures in view of the significantly higher protection it provides.

Comparison of endoscopic brush cytology with biopsy for detection of Helicobacter pylori in patients with gastroduodenal diseases.

Upper GI endoscopy was performed in 50 adult patients attending the gastroenterology OPD with gastroduodenal diseases. Gastric antral mucosal brushings were taken for cytological evaluation and urea broth test followed by antral biopsy. The slides prepared were stained with Wright Giemsa (WG), Hema toxylin & Eosin (H&E) and Papanicolaou (Pap). Brush Cytology Smears were compared with biopsy sections for detection of Helicobacter pylori and the staining techniques were evaluated to see which stain was easiest to perform and interpret on routine basis. H&E stained sections were examined for histomorphological parameters associated with H. pylori infection. Brush cytology was rapid and simple with observed sensitivity of 90% and specificity of 100%. On evaluating the various stains, M.B. and W.G. were found to the rapid and easy to perform and the bacteria stood out very well against the background. Of the histomorphological parameters studied, presence of actively and lymphoid aggregates and absence of intestinal metaplasia correlated positively with the presence of the bacteria. Cytological brushing urea broth test was not very sensitive (55.2%) and specific (51%) for detection of the bacteria.

Breast cancer in developing population: A nutrition caveat.

From January 1992-January 1998, 1404 patients attended the "Breast Clinic" of R.N.T. Medical College M.B. Hospital, Udaipur. Out of these, 11% and 81% patients had breast cancer (B.C.) and benign breast cancer (B.B.D.) respectively. The oxidative load in B.C. was 2.32 times higher than controls, but comparable to B.B.D. ß-Carotene deficiency was uncommon in patients, whereas vitamin A deficiency was almost equally common in both B.C. and controls. Most of the patients had almost depleted levels of α-tocopherol and ascorbic acid but their TBAR levels were in normal range. The data in the present study when compared with B.B.D. and other local normal subjects point out: a) oxidative burden in B.C. is a consequence and not the cause of the disease, (b) oxidative stress could be one of the etiological factors in tumor expression, which need not to be malignant and c) α-tocopherol and ascorbic acid are not importantly responsible for higher oxidative burden in B.C.

CSF interleukin-1 beta, tumor necrosis factor-alpha and free radicals production in relation to clinical outcome in acute bacterial meningitis.

OBJECTIVE: To study the relationship of CSF IL-1 beta and TNF-alpha with free radicals in acute bacterial meningitis (ABM) and to evaluate the clinical outcome in relation to the levels of these cytokines and free radicals in CSF. DESIGN: Prospective with controls. SETTING: Referral unit of a teaching hospital. METHODS: 32 children between 3m-12 yrs of age with proven acute bacterial meningitis comprised the study group. In the control group, 20 children with febrile seizures were included. CSF cytokines- Interleukin Ib and tumour necrosis factor a,free radicals O(2)-, H(2)O(2) and enzymes SOD and CPK were measured in all the children. RESULTS: CSF IL-Ib and TNF-a concentration were markedly elevated in children with ABM (441.5 +/- 216.1 pg/ml, and 1009 +/- 529.1 pg/ml, respectively) as compared to controls (52.67 +/- 6.92 pg/ml, and 86.42 +/- 16.24 pg/ml) (p <0.0001). Free radicals viz., superoxide anion, hydrogen peroxide production and enzymes creatinine phosphokinase and superoxide dismutase were also significantly elevated in ABM as compared to controls. There was direct correlation of CSF cytokines with CSF cytology, protein and free radicals production in ABM. Patients who expired or had neurological sequelae had markedly elevated concentrations of cytokines and free radicals. CONCLUSION: IL-I beta, TNF-alpha and free radicals are significantly elevated in CSF of patients with ABM. The concentration of these cytokines correlated well with free radical production, and with routinely measured CSF parameters and had a direct bearing on outcome of ABM

Incidence of HTLV-I in high-risk population in Delhi.

Human infection due to HTLV-I occurs by transmission of infected T-cells via sexual intercourse, blood transfusion or breastfeeding. The present investigation was carried out to find the incidence of HTLV-I in high risk population and its relationship with syphilis and HIV infection. The study group comprised 124 antenatal cases, 9 patients attending Sexually Transmitted Disease (STD) clinics and 144 blood donors. Passive particle agglutination test was performed on all the test sera for anti HTLV-I antibodies. VDRL and Treponema pallidum haemagglutination tests were carried out on sera from antenatal and STD cases. Sera from blood donors were tested for HIV antibodies by ELISA and confirmed by Western Blot. Anti HTLV-I antibodies were found in 10.6% of the cases studied. There was no association between the presence of anti HTLV-I antibodies and syphilis in expectant mothers and STD cases. However, significant association was found between the former and HIV infection in blood donors.

Serum TNF-alpha and free radical scavengers in neonatal septicemia.

Tumor necrosis factor-alpha (TNF-alpha) and free radicals have been implicated in the pathogenesis of neonatal septicemia and its complications. This case control study was conducted between November 1996 to July 1997 to determine the levels of TNF-alpha and free radical scavengers viz. superoxide dismutase (SOD) and glutathione peroxidase (GPX) in the serum of 30 septic neonates and 20 healthy controls. Patients with neonatal sepsis registered significantly higher levels of TNF-alpha, SOD and GPX in comparison to controls (p < 0.05). The neonates with septic shock had five fold increase in TNF-alpha levels (2262 +/- 605.8 pg/ml) as compared to those without shock (738.8 +/- 728.8 pg/ml). There was no statistically significant difference in levels of antioxidant enzymes between neonates with shock and without shock. The levels of TNF-alpha and antioxidant enzymes were not affected by the type of organism isolated in blood culture.

An outbreak of post-surgical wound infections due to Mycobacterium abscessus.

An outbreak of post-operative wound infections due to Mycobacterium abscessus is described. During a 5-month period 45 post-surgical patients developed wound infection, manifested by wound breakdown, cellulitis, and discharge and progressing slowly to suppuration and sinus formation. The majority (43/45) had undergone out-patient operations, and 40 had had surgery in the inguinal region. The source of infection was identified as contaminated tap water. A study revealed serious deficiencies in the disinfection and sterilisation techniques employed in the operating theatre (OT), including major defects in the autoclaving machine. The outbreak was controlled after several specific measures were instituted. The patients responded well to treatment with conventional first-line anti-tuberculous drugs administered for 3-8 months. The report highlights the necessity of strict monitoring of disinfection and sterilisation techniques in surgical units and OTs.

Phototoxicity of some novel porphyrin hybrids against the human leukemic cell line TF-1.

Photodynamic induced cytotoxicity by porphyrin-DNA cross linker/intercalator hybrid diads and triads has been studied on the human leukemic cell line TF-1. Cells were incubated for 1 to 4 h with these new photosensitizers and irradiated with white light. Cell survival was assessed by the propidium iodide staining, using flow cytometry analysis. A comparison of the dark and light cell survival factor values suggests that irradiation has a significant effect on the toxicity at low concentrations for the porphyrin-chlorambucil diad and to a lesser extent at high concentrations for the porphyrin-acridone diad, the porphyrin-acridine diad and the porphyrin-cholic acid-chlorambucil triad. While the intrinsic antileukemic (via DNA cross-linking) activity of the chlorambucil moiety and the structural details may be responsible for the photoenhancement of the toxicity, the presence of acridine or acridone which are avid intercalators of DNA, is responsible for a similar effect seen for diads.

Postoperative infection in cardiac surgery: the influence of a change in prophylactic antibiotic regimen.

A total of 448 patients undergoing cardiovascular surgery were followed for the development of postoperative infection. Non-extracorporeal procedures were assigned to group 1 and open-heart procedures to group 2. The incidence of infection was compared in two groups who received prophylactic antibiotics. Patients (n = 253) received ampicillin alone (group 1) or in combination with gentamicin (group 2) for 7 days starting 1 day before the operation (period A). One hundred and ninety-five patients (period B) received cefazolin starting preoperatively 30 min before induction, alone (group 1) or in combination with gentamicin (Group 2) for 3 days. The percentage of patients developing infection in periods A and B for group 1 patients was 4.2% and 3.5% and for group 2 it was 25.8% and 18.7% respectively. The overall infection rate was 13%. The number of infection sites involved were 1.5 per infected patient. Urinary tract infections were the most frequent followed by endocarditis and other deep infections, wound infections and respiratory infection. Gram-negative rods were the predominant pathogens (Klebsiella spp. and Pseudomonas aeruginosa) during both periods (47 out of 70 isolates). Wound infections due to Gram-positive cocci were higher in period A (4/8) as compared to period B (1/5). During period B there were three cases of fungal endocarditis whereas no case occurred during period A. Although the incidence of infection was reduced during the period of cefazolin prophylaxis, the difference was not statistically significant.

Aspergillus endocarditis after open heart surgery: an epidemiological investigation.

The occurrence of aspergillus endocarditis in four patients after open heart surgery, within a period of 10 months, in a centre where no case had been encountered in the previous 7 years, led us to investigate the possible source and factors contributing to this 'outbreak'. The ventilation system, air conditioning plant, air and inanimate sources in the operating theatre were investigated. With the exception of the operating room which was fitted with laminar air flow, it was possible to isolate Aspergillus spp. from all rooms in the operating suite. Air conditioner cooling coils and pigeon droppings on the ledges outside the suite were found to harbour aspergillus spores in large amounts. The ubiquitous presence of Aspergillus spp. in the operating suite indicated that the existing ventilation system was ineffective in eliminating aspergillus spores from the operating environment. The use of a newly introduced broad spectrum antibiotic protocol seemed to be a major contributory factor according to incidental evidence (although no case control studies were done). Improvements in the ventilation system and the restriction of newly introduced antibiotics was recommended. No further case of fungal endocarditis was observed up to the time of reporting (6 months after the last case).