Multi-center comparative evaluation of subgingivally delivered sanguinarine and doxycycline in the treatment of periodontitis. I. Study design, procedures, and management

The design and conduct of a 9-month multi-center clinical trial to evaluate the safety and efficacy of subgingivally delivered 5% sanguinarium chloride (SC) and 10% doxycycline hyclate (DH) from a biodegradable drug delivery system in the treatment of adult periodontitis is described. The 3-group randomized study of 180 adults with moderate to severe periodontitis was a modified double-blind parallel design. One group received DH, one group received SC, and the other group received the vehicle control (VC). Patients selected had two quadrants with a minimum of four periodontal pockets > or = 5 mm in depth with two sites > or = 7 mm. All qualifying sites exhibited bleeding on gentle probing. Qualifying sites were treated at baseline and again at 4 months. Clinical response was assessed by measuring attachment level, probing depth, and bleeding on probing at monthly examinations at qualifying sites and the entire dentition. The plaque index was measured monthly to verify oral hygiene status. The parallel design afforded the opportunity to distinguish between treatment effectiveness of SC, DH, and VC independent of possible crossover effects. Also the effectiveness of oral hygiene in untreated sites of the mouth could be evaluated. Finally, treatment effects in moderate (5 to 6 mm) and deep (> or = 7 mm) pockets in both treated and untreated sites could be compared. The design was capable of simulating a periodontal practice maintenance program and assessing the response according to maintenance and treatment history. Study management procedures that emphasized center examiner and therapist training and adherence to protocol and procedures to reduce variability are described.     

A model of litter size distribution in cattle

Genetic increases in twinning of cattle could result in increased frequency of triplet or higher-order births. There are no estimates of the incidence of triplets in populations with genetic levels of twinning over 40% because these populations either have not existed or have not been documented. A model of the distribution of litter size in cattle is proposed. Empirical estimates of ovulation rate distribution in sheep were combined with biological hypotheses about the fate of embryos in cattle. Two phases of embryo loss were hypothesized. The first phase is considered to be preimplantation. Losses in this phase occur independently (i.e., the loss of one embryo does not affect the loss of the remaining embryos). The second phase occurs after implantation. The loss of one embryo in this stage results in the loss of all embryos. Fewer than 5% triplet births are predicted when 50% of births are twins and triplets. Above 60% multiple births, increased triplets accounted for most of the increase in litter size. Predictions were compared with data from 5,142 calvings by 14 groups of heifers and cows with average litter sizes ranging from 1.14 to 1.36 calves. The predicted number of triplets was not significantly different (chi2 = 16.85, df = 14) from the observed number. The model also predicted differences in conception rates. A cow ovulating two ova was predicted to have the highest conception rate in a single breeding cycle. As mean ovulation rate increased, predicted conception to one breeding cycle increased. Conception to two or three breeding cycles decreased as mean ovulation increased because late-pregnancy failures increased. An alternative model of the fate of ova in cattle based on embryo and uterine competency predicts very similar proportions of singles, twins, and triplets but different conception rates. The proposed model of litter size distribution in cattle accurately predicts the proportion of triplets found in cattle with genetically high twinning rates. This model can be used in projecting efficiency changes resulting from genetically increasing the twinning rate in cattle.     

Penicillium species in mosquitoes from two Brazilian regions

Complaint of a burning mouth is an increasingly common problem in the aging population. This has remained an enigma for the treating clinician, because visible pathologic lesions or processes are usually not evident. Local, systemic and environmental causes must be assessed to elicit the predisposing factors. Some suggestions for managing burning mouth syndrome are offered.     

A nitric oxide synthesis inhibitor (L-NAME) reduces licking behavior and Fos-labeling in the spinal cord of rats during formalin-induced inflammation

Formalin injected subcutaneously into the hindpaw of the rat produces an animal model of inflammation that exhibits a phasic component and a tonic component of pain. We evaluated the effects of a nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), on a formalin-induced behavior, hindpaw licking, and on Fos-labeling of nuclei in the fifth lumbar spinal segment. Our results demonstrated that pretreatment with intrathecal doses of 0.3 and 1.0 mg of L-NAME significantly reduced licking behavior associated with injection of formalin into the left hindpaw of the rat. In addition, these same doses of L-NAME reduced formalin-induced Fos-labeling in the ipsilateral dorsal gray matter (as compared to the contralateral gray matter). Qualitative assessment suggested that the reduction in labeling occurred primarily in the superficial dorsal horn. The stereoisomer, D-NAME, administered at the same doses had little to no effect on either formalin-induced licking or Fos-labeling. Finally, our results revealed that total licking time was related to Fos-labeling. Rats that spent less time licking the hindpaw exhibited a smaller increase in Fos-labeling. Our results suggest that the production of nitric oxide is associated with licking behavior resulting from formalin injection into the hindpaw of rats. Our results also suggest that the production of nitric oxide and Fos are associated. Indeed, these substances may be involved in spinal pathways associated with nociception.     

The effect of stimulatory electrode placement on F-wave latency measurements

BACKGROUND AND PURPOSE: The purpose of this study was to compare the effects of two commonly used stimulating electrode placements on F-wave latency. SUBJECTS: Fifty healthy subjects aged 20 to 47 years were tested. METHODS: F-waves were obtained from median and ulnar nerves bilaterally. A total of 200 nerves were tested. RESULTS: A paired t-test indicated a statistically significant difference in F-wave latency between the two stimulating electrode placements. Stepwise linear regression equations demonstrated that our results were consistent with previously published studies. CONCLUSION AND DISCUSSION: Although a statistically significant difference exists between the two techniques, the magnitude of the difference is not likely to be clinically important. Therefore, the most important factor may be to use a consistent technique when investigating potential neuropathies.     

Cytokine regulation of human microglial cell IL-8 production

IL-8 involvement in neutrophil activation and chemotaxis may be important in inflammatory responses within the central nervous system, secondary to meningitis, encephalitis, and traumatic injury. The source of IL-8 within the brain during these inflammatory processes, however, is unknown. To explore the role of microglia in the production of IL-8, human fetal microglia, which are the resident macrophages of the brain, were treated with LPS and pro- and anti-inflammatory cytokines to determine their effects on IL-8 production. We found that IL-8 protein levels increased in response to LPS or IL-1 beta, or to TNF-alpha, which also corresponded to elevated IL-8 mRNA levels by RT-PCR. Pretreatment with IL-4, IL-10, or TGF-beta 1 potently inhibited the stimulatory effects of these proinflammatory agents. These findings indicate that human microglia synthesize IL-8 in response to proinflammatory stimuli, and that anti-inflammatory cytokines down-regulate the production of this chemokine. These results may have important therapeutic implications for certain central nervous system insults involving inflammation.     

The Ultracor tilting disc heart valve prosthesis: a seven-year study

This review aims to explain why H1 histone can be considered as a protein involved in protecting genomic DNA from full methylation. Some of our results indicated that, to explain the multiple roles in which H1 histone seems to be involved, it is important to consider that it is not a unique protein but a family of genetic somatic variants and that every one of them can be dynamically modified by different post-synthetic enzymatic modifications. Our data show that H1 histone plays an inhibitory effect on DNA methylation through its H1e variant and that poly(ADP-ribosyl)ation is a post-synthetic modification involved in this regulatory role. The idea that the poly(ADP-ribosyl)ated isoform of H1e could be present in decondensed chromatin structure, where the housekeeping genes are located, will be discussed.     

Lamivudine treatment for acute hepatitis B after liver transplantation

Although epidemiological and experimental studies indicate a strong relationship between different dietary fats and risk of colon cancer, the modulating effects of these nutritional factors at the molecular level are not fully elucidated. Activated ras genes have been implicated in the etiology of many human malignancies, including colon cancer. It is well established that the transforming ability of ras-p21 depends on its correct localization in plasma membrane. We have previously demonstrated that ingestion of a relatively higher amount of dietary fish oil leads to reduced plasma membrane levels of ras-p21 with concomitant increase in its cytoplasmic contents during the promotion and progression phases of chemically-induced colon tumorigenesis. In this follow-up experiment, we have found that intake of a high amount of corn oil, one of the most widely used fats in the American diet, enhances the expression of farnesyl protein transferase (FPTase). This enzyme catalyses farnesylation of ras precursors in a critical step during post-translational modification of ras oncoproteins, thereby enabling their anchorage to plasma membrane. In contrast, consumption of high amounts of fish oil, which is rich in omega-3 polyunsaturated fatty acids, reduces the levels of FPTase expression, thus inhibiting post-translational processing of ras precursors resulting in decreased ras function both in colonic mucosa as well as in colon tumors. These results correlate with increased incidence and multiplicity of grossly visibly colon tumors in carcinogen-treated animals fed a high corn oil diet versus decreased incidence and multiplicity of colon tumors in their counterparts fed the high fish oil diet. This dietary inhibition of FPTase may have a practical chemopreventive potential.