Involvement of capsaicin-sensitive afferent nerves and cholecystokinin 2/gastrin receptors in gastroprotection and adaptation of gastric mucosa to Helicobacter pylori-lipopolysaccharide

Lipopolysaccharide (LPS) is one of the virulence factors in the Helicobacter pylori (Hp)-infected stomach, but it remains unknown whether single and prolonged pretreatment with Hp-LPS can affect the course of gastric damage induced by aspirin (ASA). We compared the effects of Hp-LPS with those induced by LPSs isolated from intestinal Bacteroides fragilis, Yersinia enterocolitica, and Campylobacter jejuni applied for 4 days on acute ASA-induced gastric lesions in rats. The area of ASA-induced gastric lesions, gastric blood flow (GBF), expression of mRNA and protein of leptin and plasma leptin, gastrin, interleukin-1beta, and tumor necrosis factor-alpha levels were examined. Single (once) or repeated (five times) i.p. injections of Hp-LPS (1 mg/kg) or intestinal LPSs failed to produce macroscopic gastric damage and did not affect the GBF when compared with vehicle. Hp-LPS injected repeatedly suppressed the gastric acid secretion, up-regulated leptin mRNA and protein, and increased plasma leptin and gastrin levels. Hp-LPS significantly reduced the ASA-induced gastric damage and the accompanying decline in the GBF, and these effects were significantly attenuated by capsaicin denervation and selective antagonism of cholecystokinin-B (CCK2) receptors by RPR-102681 [N-(metoxy-3 phenyl) N-(N-methyl N-phenyl-carbamylmethyl) carbamoylmethyl]-3 ureido]-3 phenyl]-2 propronique] but not by loxiglumide, an antagonist of CCK1 receptors. We conclude that 1) daily application of Hp-LPS enhances gastric mucosal resistance against ASA damage due to the increase of GBF and the expression and release of leptin and gastrin exerting trophic and gastroprotective effects, and 2) this enhanced resistance to ASA damage in Hp-LPS-adapted stomach is mediated by the sensory afferents and specific CCK2/gastrin receptors.     

Neuroendocrinology of gastric H+ and duodenal HCO3- secretion: the role of brain-gut axis

Gastric H+ and duodenal HCO3- secretions are precisely regulated by neuro-hormonal mechanisms at central and peripheral levels to match the rate of these secretions with the type of stimulation of sensory receptors in the head area (sight, smell, taste, etc.) and in the gastro-intestinal system. Two-way communication pathways operate between the brain and the gut, each comprising afferent fibers signaling sensory information from the gut to the brain and efferent fibers transmitting signals in opposite direction. Short intramural and long extramural reflexes are triggered as well as various gut hormones are released by feeding that "cooperate" with the "brain-gut axis" in the alteration of exocrine and endocrine gastro-duodenal secretion, motility and blood circulation. The malfunction of gastric or duodenal secretory mechanisms may lead to disturbances of gastric H+-pepsin or duodenal mucus-HCO3- secretion and to gastro-duodenal disorders and diseases. This review presents recent advances in pathophysiological mechanisms underlying gastro-duodenal secretory disorders.     

Phase II study of antineoplaston A10 and AS2-1 in children with recurrent and progressive multicentric glioma : a preliminary report

OBJECTIVE: To evaluate the response rates, survival and toxicity of treatment with antineoplaston A10 and AS2-1 (ANP) in the first 12 children enrolled in our studies diagnosed with incurable recurrent and progressive multicentric glioma. PATIENTS AND METHODS: The patients' median age was 9 years. Six patients were diagnosed with pilocytic astrocytoma, four with low-grade astrocytoma and one with astrocytoma grade 2. In one case of visual pathway glioma, a biopsy was not performed due to a dangerous location. Patients received ANP intravenously initially and subsequently orally. The average duration of intravenous ANP therapy was 16 months and the average dosage of A10 was 7.95 g/kg/day and of AS2-1 was 0.33 g/kg/day. The average duration of oral ANP was 19 months and the average dosage of A10 and AS2-1 was 0.28 g/kg/day. Responses were assessed by MRI according to the National Cancer Institute's criteria and confirmed by PET scans in some cases. RESULTS: Complete response was accomplished in 33%, partial response in 25%, and stable disease in 33% of patients, and there was no progressive disease. One patient was non-evaluable due to only 4 weeks of ANP and lack of follow-up scans. One patient who had stable disease discontinued ANP against medical advice and died 4.5 years later. Ten patients are alive and well from 2 to >14 years post-diagnosis. Only one case of serious toxicity of reversible tinnitus, of one day's duration, was described. The study continues with accrual of additional patients. CONCLUSION: The results of the present study are favourable in comparison with radiation therapy and chemotherapy. We believe that confirmation of these results through further studies may introduce a new promising treatment for incurable paediatric brain tumours.     

The present state of antineoplaston research (1)

Antineoplastons work as molecular switches, which regulate expression of genes p53 and p21 through demethylation of promoter sequences and acetylation of histones. They also inhibit the uptake of growth-critical amino acids, such as 1-glutamine and 1-leucine in neoplastic cells. Phase II trials indicate efficacy of antineoplastons in low-grade glioma, brain stem glioma, high-grade glioma, adenocarcinoma of the colon, and hepatocellular carcinoma. The best results were observed in children with low-grade glioma, where 74% of patients obtained objective response, and in patients with adenocarcinoma of the colon with liver metastases whose survival rate of more than 5 years is 91% versus 39% in controls on chemotherapy. Gene array studies will explain antineoplaston-induced changes in gene expression.     

Relationship of paternal factors to birth weight

OBJECTIVE: To investigate the relationship between paternal characteristics and birth weight. STUDY DESIGN: A total of 241 gravidas with uncomplicated, singleton, term pregnancies were studied. Maternal demographic and pregnancy-specific characteristics were used to calculate the expected birth weight for each fetus using a previously validated birth weight prediction equation. The additional independent predictive value of 4 paternal variables was assessed using multiple regression. RESULTS: Before adjustment for other variables, paternal height and weight significantly correlated with birth weight, but paternal age and body mass index did not. After controlling for maternal and pregnancy-specific factors that are known to influence fetal weight, only paternal height was significant as a predictive variable. The proportion of variance in birth weight that could be independently explained by paternal height was 2%. A 10-g gain in fetal weight was associated with each centimeter of increase in paternal height (P < .02). Using the resulting combination equation that included paternal height as a variable, 31% of the variance in term birth weight could be explained, and birth weights could be accurately predicted to within +/- 8.3% (+/- 288 g). Fathers with heights 2 SD above and below the mean had the term birth weight of their offspring increased and diminished by 125 g, respectively. CONCLUSION: Paternal height explains an independent portion of the variance in term birth weight among normal newborns of up to 250 g that cannot be explained by other maternal or pregnancy-specific factors. Paternal age, weight and body mass index do not independently influence birth weight.     

Early-pregnancy glucose screening for gestational diabetes mellitus

OBJECTIVE: To determine the accuracy of the 50-g, one-hour glucose screening test administered at 16 weeks of pregnancy for identifying women with gestational diabetes mellitus. STUDY DESIGN: Two hundred fifty-five women underwent 50-g, one-hour glucose screening tests at 16 weeks of pregnancy. Those with results > or = 135 mg/dL underwent 100-g, three-hour glucose tolerance tests. All patients without diagnoses of gestational diabetes during the second trimester of pregnancy underwent standard third-trimester glucose testing. RESULTS: Gestational diabetes mellitus was diagnosed in 25 patients. Glucose screening tests administered at 16 weeks of pregnancy identified 96% (24) of these patients. Patients with 16-week glucose screening test results > or = 135 mg/dL had a 55% risk of developing diabetes during pregnancy, while the risk was 0.6% for patients with 16-week test results < or = 110 mg/dL. Patients with 16-week glucose screening test results in the intermediate range, 111-134 mg/dL, had a 4.8% risk of developing diabetes during pregnancy. CONCLUSION: Glucose screening at 16 weeks of pregnancy is a useful alternative to third-trimester screening for gestational diabetes. The negative predictive value of screening test results < or = 110 mg/dL is 99.4%. The positive predictive value for screening test results > or = 135 mg/dL is 55%. This latter finding is superior to the 8.6-22% found during the third-trimester.     

Near-infrared thermo-optical response of the localized reflectance of intact diabetic and nondiabetic human skin

We observed a difference in the thermal response of localized reflectance signal of human skin between type 2 diabetics and nondiabetics. We investigated the use of this thermo-optical behavior as the basis for a noninvasive method for the determination of the diabetic status of a subject. We used a two-site temperature differential method, which is predicated upon the measurement of localized reflectance from two areas on the surface of the skin. Each of these areas is subjected to a different thermal perturbation. The response of localized reflectance to temperature perturbation was measured and used in a classification algorithm. We used a discriminant function to classify subjects as diabetic or nondiabetic. In a prediction set of twenty-four noninvasive tests collected from six diabetic and six nondiabetic subjects, the sensitivity ranged between 73 and 100%, and the specificity ranged between 75 and 100%, depending on the thermal conditions and the probe-skin contact time. The difference in the thermo-optical response of the skin of the two groups is explained in terms of a difference in the response of cutaneous microcirculation, which is manifested as a difference in the near-infrared light absorption. Another factor is the difference in the temperature response of the scattering coefficient between the two groups, which may be caused by cutaneous structural differences induced by nonenzymatic glycation of skin protein fibers, and possibly by the difference in blood cell aggregation.     

Is the functional connectivity within temporal lobe influenced by saccadic eye movements?

Local evoked potentials (LEPs), recorded in response to electrical stimulation, were used to study functional connectivity between different sites of the temporal lobe. Permanent electrodes were implanted in anterior and posterior positions of both inferotemporal cortex (IT) and hippocampal formation (HF). In each experimental session, one of these four sites was stimulated and LEPs were recorded in the others. Clear LEPs were found in the anterior and posterior IT sites in response to stimulation of the anterior as well as posterior HF. Bidirectional connections (as judged by the potentials) were found between the anterior and posterior sites of the same structure (IT or HF). The timing of the LEPs indicates that much of the response was carried in multisynaptic circuits. Stimulation delivered just after the monkey made a saccade produced larger late components in the LEPs than the same stimulation delivered without a saccade. The influence was maximal when the delay between the end of the saccade and the electrical stimulation was in the range of 50-100 ms. This saccadic modulation of the functional connectivity was observed within IT (bidirectional) and between posterior HF and IT (unidirectional).