Protein-calorie malnutrition impairs host defense against Candida albicans.

Protein-calorie malnutrition (PCM) impairs immune responsiveness predisposing to Candida albicans sepsis, but mechanisms are unclear. This study examined the effect of PCM on enteric-derived C. albicans intestinal translocation and the ability of in vivo interferon-gamma (IFN-gamma) to upregulate macrophage (MO) candidacidal mechanisms in PCM mice. Control (24% casein) and low protein (2.5%) diets were given for 4 weeks. Mice (n = 160) were fed C. albicans in their drinking water for 3 days and C. albicans translocation (mean colony-forming units (CFU)/g tissue +/- SEM) to the GI tract, liver, spleen, and kidney was assessed at 1 and 5 days following endotoxin challenge of 1, 5, and 10 mg/kg body wt. In a separate study (n = 100 mice), IFN-gamma (1000-10,000 U/day ip) vs saline was given for 3 days prior to harvesting peritoneal macrophages for assay of superoxide anion (O2-), percentage macrophage phagocytosis of C. albicans, and percentage killing of C. albicans. On Day 1, fungal translocation to the intestinal wall and systemic organs in the PCM group was significantly higher. On Day 5, mean CFU were significantly higher in the PCM group, indicating impaired organ clearance. Mean O2-, phagocytosis, and killing were significantly impaired in the PCM group (P less than 0.05), but IFN-gamma improved all functions. PCM significantly depressed host responses to C. albicans. IFN-gamma treatment enhanced candidacidal mechanisms, suggesting a therapeutic role in the malnourished host predisposed to C. albicans sepsis.     

The effect of sodium fluoride on trabecular architecture.

The effect of sodium fluoride therapy on iliac trabecular bone has been studied in 15 patients with primary osteoporosis by comparing bone biopsies taken before and after two years of treatment. A marked increase in bone volume (43%) was observed, which was attributable to an increase in trabecular thickness (46%) rather than their number. Because the trabecular bone surface, the trabecular number, the bone volume/trabecular width ratio, and the trabecular terminus number do not change significantly after fluoride treatment, we conclude that fluoride does not induce the de novo generation of trabeculae, nor does it restore trabecular connectivity despite the restoration of bone mass. These data suggest that the restoration of skeletal mass with fluoride may not lead to a comparable decrease in the risk of future fracture.     

Studies of pickled vegetables and cause of esophageal cancer in Linxian. II. Determination of nitrosamines and their precursors]

Pickled vegetables are daily food consumed in the high-risk areas for esophageal cancer in China. We analyzed the nitrosamine content of Linxian pickles by GC/TEA and found that trace amounts of six nitrosamines (NDMA, NDEA, NMBA, NMAMBA, NDPA, NPYR) were present, with the highest concentrations being NDMA and NDEA (1.7 and 1.9 micrograms/kg wet weight respectively). The average level of nitrosamine precursors, such as nitrate (111.22 mg/L), nitrite (0.152 mg/L) and secondary amines (4.223 mg/L), in pickled vegetables were determined, and their pH values ranged from 3 to 5.     

The precision of positron emission tomography: theory and measurement

The limits of quantitation with positron emission tomography (PET) are examined with respect to the noise propagation resulting from radioactive decay and other sources of random error. Theoretical methods for evaluating the statistical error have been devised but seldom applied to experimental data obtained on human subjects. This paper extends the analysis in several ways: (1) A Monte Carlo method is described for tracking the propagation of statistical error through the analysis of in vivo measurements; (2) Experimental data, obtained in phantoms, validating the Monte Carlo method and other methods are presented; (3) A difference in activation paradigm, performed on regional CBF (rCBF) data from five human subjects, was analyzed on 1.6-cm diameter regions of interest to determine the mean fractional statistical error in PET tissue concentration and in rCBF before and after stereotactic transformation; and (4) A linear statistical model and calculations of the various statistical errors were used to estimate the magnitude of the subject-specific fluctuations under various conditions. In this specific example, the root mean squared (RMS) noise in flow measurements was about three times higher than the RMS noise in the concentration measurements. In addition, the total random error was almost equally partitioned between statistical error and random fluctuations due to all other sources.     

Buprenorphine responders: a diagnostic subgroup of heroin addicts?

1. A 26-32 month follow-up of 16 heroin-dependent subjects who entered a pilot trial of treatment with buprenorphine (a mixed agonist/antagonist) suggests that positive response to treatment may identify a subgroup of untreated addicts whose levels of psychosocial functioning are intermediate between those for whom methadone (a pure agonist) or naltrexone (a pure antagonist) would be indicated. 2. Buprenorphine's pharmacologic profile provides a missing link in available modalities for opiate dependence treatment, making it acceptable for many addicts who will not accept methadone maintenance treatment, join a residential therapeutic community, or be successful on naltrexone treatment. 3. Eight of the 16 ss were abstinent from heroin while receiving 0.6-3.9 mg/day buprenorphine and counseling. Responders (mean age 34 yrs) had been heroin dependent for a mean of 9.5 years (range 6-17 yrs), all were self-supporting, 4 lived with a non-addicted spouse, 5 had no prior treatment for addiction and 3 had prior naltrexone treatment, but had discontinued it and relapsed. Non-responders (mean age 30 yrs) had been heroin dependent for a mean of 7.4 yrs (range 2-19 yrs), 7 had no regular employment, all were single and 7 had no prior treatment for addiction. 4. Levels of psychosocial functioning (work, home, leisure) and global assessments of functioning were significantly higher for buprenorphine responders than non-responders (p less than .001 and p less than .01 respectively). 5. A new formulation of buprenorphine needs to be developed for addiction treatment, ideally consisting of 0.5 mg and 2.0 mg sublingual tablets.     

Singlet oxygen induced cerebral vasospasm: an experimental study in rats

A new experimental model is described which can be used as an alternative to study the effects of subarachnoid hemorrhage (SAH) in rats. Vasospasm of the basilar artery is induced photochemically after transpalatal illumination of intracisternally injected rose bengal in two different rat strains. Singlet oxygen, generated in the subarachnoid space, elicits vasospasm which has been demonstrated angiographically at 90 min and 24 h after photosensitisation. Sprague Dawley rats responded better than Wistar rats. Dilution of rose bengal in water was more vasospastic than dilution of rose bengal in artificial CSF. Since the action of singlet oxygen is similar to that of free radicals, this experiment gives an argument for the hypothesis that free radicals play a leading role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage.     

Transport of estrogen-induced oxytocin receptors in the ventromedial hypothalamus.

The modulation of oxytocin (OT) receptors (OTRs) by estrogen was investigated in the ventromedial hypothalamus by in vitro receptor autoradiography. Treatment of ovariectomized and adrenalectomized rats with various doses of estradiol benzoate (EB) increased OTR binding not only in the ventromedial nuclei of the hypothalamus (VMN), but also in the area lateral to the nuclei (IVMN). After a single injection of EB, OTRs first were induced within the ventrolateral parts of the VMN, and only hours later they appeared in the IVMN. This is consistent with the interpretation that OTRs are first induced within the estrogen-sensitive neurons of the ventrolateral VMN and then are transported laterally out of the nuclei. Two additional experiments confirmed this interpretation. First, local infusion of a low dose (10 micrograms) of the neuronal transport inhibitor vinblastine blocked the appearance of OTRs in the IVMN but did not prevent the induction of OTRs by EB within the nuclei. Second, a knife cut placed lateral to the VMN prevented the spread of OTRs out of the nuclei. However, even after treatment with a high dose of EB (2 x 10 micrograms), progesterone (P) was required for a maximal extension of the area covered by OTRs. Thus, the OTR is an estrogen-induced neurotransmitter receptor that is transported to its site of action, the lateral ventromedial hypothalamus, where it is modulated by P and where estrogen-induced OT immunoreactivity is found.     

Single odor-sensitive channels in olfactory receptor neurons are also gated by cyclic nucleotides.

Olfactory transduction is thought to occur by processes that are mainly restricted to the specialized cilia emanating from the distal end of the receptor neuron's single dendrite. The involvement of a cAMP-based second messenger system seems likely, and a cyclic nucleotide-sensitive current has been recorded in patches of membrane from the cilia. However, the small diameter of the cilia and the high density of channels within the membrane limit the application of the patch recording technique in the cilia. We have found that the cAMP-sensitive channels also exist at a much lower density within the far more accessible dendritic membrane. Recording from on-cell patches, we have observed single-channel activity in response to extracellularly applied odor substances. The channels have a single-channel conductance of 40 pS and a reversal potential near 0 mV. These same channels are activated by treatments that elevate intracellular cyclic nucleotide concentrations. The results provide a direct demonstration that the cyclic nucleotide-gated channel is the conductance pathway for the odor-elicited current.