Calcium inhibits promotion by hot dog of 1,2‐dimethylhydrazine‐induced mucin‐depleted foci in rat colon

Epidemiology suggests that processed meat is associated with colorectal cancer risk, but few experimental studies support this association. We have shown that a model of cured meat made in a pilot workshop promotes preneoplastic lesions, mucin‐depleted foci (MDF) in the colon of rats. This study had two aims: to check if real store‐bought processed meats also promote MDF, and to test if calcium carbonate, which suppresses heme‐induced promotion, can suppress promotion by processed meat. A 14‐day study was done to test the effect of nine purchased cured meats on fecal and urinary biomarkers associated with heme‐induced carcinogenesis promotion. Fecal water from rats given hot dog or fermented raw dry sausage was particularly cytotoxic. These two cured meats were thus given to rats pretreated with 1,2‐dimethylhydrazine, to evaluate their effect on colorectal carcinogenesis. After a 100‐days feeding period, fecal apparent total N‐nitroso compounds (ATNC) were assayed and colons were scored for MDF. Hot dog diet increased fecal ATNC and the number of MDF per colon compared with the no‐meat control diet (3.0 ± 1.7 vs. 1.2 ± 1.4, p < 0.05). In a third study, addition of calcium carbonate (150 µmol/g) to the hot dog diet decreased the number of MDF/colon and fecal ATNC compared with the hot dog diet without calcium carbonate (1.2 ± 1.1 vs. 2.3 ± 1.4, respectively, p < 0.05). This is the first experimental evidence that a widely consumed processed meat promotes colon carcinogenesis in rats. It also shows that dietary prevention of this detrimental effect is possible.     

Far-field Potentials as a Method of Monitoring Acute and Chronic Spinal Cord Injury

Far-field potentials (FFPs) were studied in monkeys to determine the utility of such responses in evaluating acute and chronic spinal cord injury. Monkeys (Macaca fascicularis) were anesthetized with 70% N₂O 30% O₂, immobilized with pancuronium bromide, and maintained on a respirator. Spinal cord transections were made at level T₃-T₄ and included bilateral dorsal columns or anterolateral columns, right or left hemisection, or central cord lesions. Percutaneous stimulation of both posterior tibial nerves was performed at a frequency of 3 Hz using 3-4 mA for 0.3 msec duration. Potentials were recorded from chronically implanted epidural electrodes (right ear reference) through a 300-3,000 Hz band pass filter. Each far-field potential represents the average of 256 individual responses recorded for a duration of 25 msec before and after cord lesion for up to 8 weeks.

Seven reproducible components in the far-field potential could be identified. Following dorsal column transection all components were reduced in amplitude. After anterolateral column transection only latencies were altered. Right or left hemisections caused both attenuation of component amplitudes and latency alteration. Central cord lesions resulted in no detectable amplitude or latency disturbances. Control records likewise showed no changes. No major alterations, following day 1 posttransection, were observed, attesting to the relative stability of far-field potentials over long periods of time. Far-field potentials therefore may be useful in monitoring spinal cord injury.     

An evaluation of two large scale demand side financing programs for maternal health in India: the MATIND study protocol

ABSTRACT: BACKGROUND: High maternal mortality in India is a serious public health challenge. Demand side financing interventions have emerged as a strategy to promote access to emergency obstetric care. Two such state run programs, Janani Suraksha Yojana (JSY)and Chiranjeevi Yojana (CY), were designed and implemented to reduce financial access barriers that preclude women from obtaining emergency obstetric care. JSY, a conditional cash transfer, awards money directly to a woman who delivers in a public health facility. This will be studied in Madhya Pradesh province. CY, a voucher based program, empanels private obstetricians in Gujarat province, who are reimbursed by the government to perform deliveries of socioeconomically disadvantaged women. The programs have been in operation for the last seven years.Methods/designsThe study outlined in this protocol will assess and compare the influence of the two programs on various aspects of maternal health care including trends in program uptake, institutional delivery rates, maternal and neonatal outcomes, quality of care, experiences of service providers and users, and cost effectiveness. The study will collect primary data using a combination of qualitative and quantitative methods, including facility level questionnaires, observations, a population based survey, in-depth interviews, and focus group discussions. Primary data will be collected in three districts of each province. The research will take place at three levels: the state health departments, obstetric facilities in the districts and among recently delivered mothers in the community. DISCUSSION: The protocol is a comprehensive assessment of the performance and impact of the programs and an economic analysis. It will fill existing evidence gaps in the scientific literature including access and quality to services, utilization, coverage and impact. The implementation of the protocol will also generate evidence to facilitate decision making among policy makers and program managers who currently work with or are planning similar programs in different contexts.     

Mucosal glucosamine synthetase activity in inflammatory bowel disease

Abnormalities in colonic glycoprotein synthesis have been implicated in the pathogenesis of ulcerative colitis and Crohn's disease. Glucosamine synthetase is the rate-limiting step in the biosynthesis of gastrointestinal glycoprotein and has been measured in control subjects (N=23) and patients with ulcerative colitis (N=26) or Crohn's disease of the colon (N=20) classified according to the macroscopic status of the rectum. Glucosamine synthetase activity was relatively constant around the normal colon but lower levels were found in the terminal ileum. In ulcerative colitis, glucosamine synthetase activity was similar to controls (24.0±1.9) mmol/g wet (wt/hr) irrespective of disease activity (quiescent:N=13, =27.3±1.9; activeN=16, =26.2±2.3). Rectal glucosamine synthetase activity was normal in the presence of active Crohn's proctocolitis (29.4±3.1) but raised in patients with Crohn's colitis and rectal sparing (37.2±4.9P<0.02). Glucosamine synthetase activity was strongly influence by the degree of epithelial preservation.     

Genetic Recombination in Escherichia coli: The Role of Exonuclease I

The indirect suppression of recB(-) and recB(-)recC(-) mutations by the sbcB(-) allele is caused by the loss of a nuclease active on denatured DNA. Results from enzyme purifications and studies with a specific antiserum demonstrate that the activity present in sbcB(+) strains, and lost in sbcB(-) strains, is exonuclease I. It is likely that sbcB is the structural gene for exonuclease I. The loss of exonuclease I activity restores the recombination proficiency of Escherichia coli cells that has been lost by mutations in the recB and/or recC genes. This indicates that in the absence of the recB-recC-determined enzyme, exonuclease I prevents recombination. Hypothetical pathways illustrating this conclusion are presented.     

Ethanol-withdrawal seizures are controlled by tissue plasminogen activator via modulation of NR2B-containing NMDA receptors

Chronic ethanol abuse causes up-regulation of NMDA receptors, which underlies seizures and brain damage upon ethanol withdrawal (EW). Here we show that tissue-plasminogen activator (tPA), a protease implicated in neuronal plasticity and seizures, is induced in the limbic system by chronic ethanol consumption, temporally coinciding with up-regulation of NMDA receptors. tPA interacts with NR2B-containing NMDA receptors and is required for up-regulation of the NR2B subunit in response to ethanol. As a consequence, tPA-deficient mice have reduced NR2B, extracellular signal-regulated kinase 1/2 phosphorylation, and seizures after EW. tPA-mediated facilitation of EW seizures is abolished by NR2B-specific NMDA antagonist ifenprodil. These results indicate that tPA mediates the development of physical dependence on ethanol by regulating NR2B-containing NMDA receptors.