Verapamil-induced gingival overgrowth: a clinical, histologic, and biochemic approach

Verapamil-induced overgrowth was most prominent in the anterior regions and interproximal areas associated with plaque retention. Despite periodontal therapy, overgrowths recurred 1 month after gingivectomy. Discontinuation of the drug resulted in regression of the overgrowths. Histologic findings showed inflamed connective tissue covered by an acanthotic, thickened oral epithelium with long rete pegs containing dyskeratotic pearls. The proliferation rate and protein and collagen production of fibroblasts from the overgrowth sites were markedly lower than in the control cells cultured from healthy gingiva. Incubation of fibroblasts in the presence of verapamil reduced protein and collagen synthesis.     

Fumonisin B1-induced apoptosis in neuroblastoma, glioblastoma and hypothalamic cell lines

Fumonisin B(1) (FB(1)) is a mycotoxin produced by Fusarium verticilliodes, which commonly infects corn across the world. Fusarium fungi may also be found in moisture-damaged buildings. In this study, we investigated the role of apoptosis in the toxicity of FB(1) in four different cell lines. Activation of caspase-3-like protease, DNA fragmentation and expression of p53 and Bcl-2 family proteins were studied in mouse GT1-7 hypothalamic, rat C6 glioblastoma, human U-118MG glioblastoma, and human SH-SY5Y neuroblastoma cells exposed to 0.1-100microM FB(1) for 0-144h. Caspase-3-like protease activity increased in all cell lines, except SH-SY5Y, at 48-144h, and internucleosomal DNA fragmentation occurred in all of the cell lines, pointing to a role for apoptosis in the toxicity of FB(1). However, the expressions of p53 or pro- or antiapoptotic Bcl-2 family proteins (Bax, Bcl-2, Bcl-X(L) and Mcl-1) were not affected in any of the cell lines even after prolonged exposure to FB(1) at high doses. The results of this study, together with the results of our previous studies, provide evidence that FB(1) is a potential neurotoxin, but that the toxicity of FB(1) varies between different cell lines. The sensitivity of these cell lines towards FB(1) is as follows: U-118MG>GT1-7>C6>SH-SY5Y cells. These results are consistent with the assumption that cells of glial origin may be more sensitive towards FB(1) than cells of neural origin.     

Three unrelated viruses occur in a single isolate of Gremmeniella abietina var. abietina type A

Five enclosed double-stranded RNA (dsRNA) bands in electrophoresis, probably of viral origin, were found from a single isolate (SurS4) of Gremmeniella abietina var. abietina type A. Analysis of the dsRNAs revealed that they represented three different viruses, named as Gremmeniella abietina mitochondrial RNA virus S2 (GaMRV-S2), Gremmeniella abietina RNA virus MS2 (GaRV-MS2) and Gremmeniella abietina RNA virus L2 (GaRV-L2). The genome of GaMRV-S2 was 2587 base pairs (bp) long and had a very low GC content (31%). Sequence variations occurred at both ends. The genome coded for a putative RNA-dependent RNA polymerase (RdRp) under a mitochondrial translation code. The GaRV-MS2 genome was composed of three dsRNA molecules (1781 bp, 1586 bp and 1186 bp). They coded for a putative RdRp, a coat protein (CP) and a protein with an unknown function, respectively. The GaRV-L2 genome was 5129 bp long and contained two ORFs. The 5′-proximal ORF coded for a putative CP, whereas the 3′-proximal ORF encoded for a putative RdRp. The buoyant density of GaRV-MS2 and GaRV-L2 were 1.37 and 1.42 g/ml, respectively. GaMRV-S2, GaRV-MS2 and GaRV-L2 were closely related to the previously described viruses GaMRV-S1, GaRV-MS1 and GaRV-L1, respectively, and are putative members of the genera Mitovirus, Partitivirus and Totivirus, respectively. This is the first report on the occurrence of viruses of all these different genera in a single fungal isolate.     

Acute cardiovascular responses in preterm infants at 34–39 weeks of gestational age

Background

Premature infants demonstrate immature physiological control mechanisms; however their acute cardiovascular control has not yet been widely studied.

Aim

The aim of this study was to analyze heart rate (HR) and blood pressure (BP) control in preterm infants.

Subjects

Twenty preterm infants with a mean gestational age of 31 ± 2.4 (26–34) weeks at birth were evaluated at a gestational age of 36 ± 1.5 (34–39) weeks. Results were compared to twenty, healthy, full-term, control infants studied at the age of 12 ± 3 weeks.

Outcome measures

HR and BP responses to 45° head-up tilt and side motion tests during non-rapid eye movement sleep were analyzed. In addition, HR responses to spontaneous arousals from non-rapid eye movement sleep were evaluated.

Results

Preterm infants showed significantly smaller initial HR and BP responses compared with controls in head-up tilt (HR p = 0.0005, systolic BP p = 0.02, diastolic BP p = 0.01) and side motion tests (HR p = 0.002, systolic BP p < 0.0001, diastolic BP p < 0.0001). Furthermore, in tilt tests, preterm infants presented with greater intersubject variability in BP responses than controls (systolic BP p = 0.009, diastolic BP p = 0005). Preterm HR responses to spontaneous arousals were similar to controls.

Conclusions

This study indicates immature vestibulo-mediated cardiovascular control in preterm infants compared with term infants. This is seen as attenuated BP responses to side motion test and more labile acute BP control to postural challenge.     

Cytosolic Phospholipase A2α Protects against Ischemia/Reperfusion Injury in the Heart

Studies with sPLA₂ Group X, and cPLA₂α gene‐targeted mice suggest that absence of sPLA₂ Group X results in protection from ischemia/reperfusion (I/R) injury in the heart, and absence of cPLA₂α Group IV is protective in the brain. Although latter studies might suggest a similar deleterious role for cPLA₂α in I/R injury in the heart, the pathophysiology of stroke is intricately related to excitotoxicity and cannot necessarily be extrapolated to the heart. We report here that unlike findings in the brain, cPLA₂α^(−/−) mice have exaggerated injury following I/R in vivo. In contrast, there is no difference in injury induced by simulated ischemia in cardiomyocytes isolated from cPLA₂α^(−/−) versus cPLA₂α^(+/+) mice. This suggests that cPLA₂α does not have an important cardiomyocyte autonomous effect on ischemic injury. Prostaglandin E₂ (PGE₂) levels are significantly reduced in the hearts of the cPLA₂α^(−/−) mice, and the enhanced injury is ameliorated by treatment with the PGE analog, misoprostol. We demonstrate that cPLA₂α is cardioprotective in vivo, and this is likely via cPLA₂α‐mediated production of cardioprotective eicosanoids. These studies are the first to identify a protective role for cPLA₂ in I/R injury in any organ and raise concerns over long‐term inhibition of cPLA₂. Clin Trans Sci 2011; Volume 4: 236–242     

Central adenoid cystic carcinoma of the mandible: case report and literature review of 16 cases

Central intraosseous adenoid cystic carcinoma (ACC) of the mandible, formerly known as cylindroma, is a rare neoplasm with only 16 cases reported in the literature. We describe the diagnosis, etiology, and treatment of a central ACC located in the mandibular premolar region. We also review the literature. This case illustrates 2 key facts regarding the diagnosis and etiology of ACC. First, central salivary gland tumors should be considered in the differential diagnosis of cystic lytic lesions in the mandible. Second, even though the origin of this type of tumor is still unknown, the presence of ectopic tissue anterior to the submandibular gland in the submandibular area indicates that this tumor might be made up of ectopic embryogenic inclusions.     

Mismatch negativity and late discriminative negativity in sleeping human newborns

Event-related potentials were recorded from sleeping newborns to compare amplitudes and latencies of mismatch negativity (MMN) and late discriminative negativity (LDN) in active and quiet sleep stages. MMN and LDN were obtained in response to changes in semi-synthesized vowels from 20 healthy newborn infants. MMN and LDN responses were significant for both active and quiet sleep. The amplitude and latency of MMN or LDN did not differ between the sleep stages. Thus, in contrast to adult studies that show a significant drop in the MMN amplitude and an increase in the MMN latency as the sleep gets deeper, arousal stages do not seem to effect either MMN or LDN characteristics in newborns. These results suggest functional differences between infant and adult sleep.     

Evaluation of the analgesic efficacy and psychoactive effects of AZD1940, a novel peripherally acting cannabinoid agonist,in human capsaicin‐induced pain and hyperalgesia

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Design, Synthesis and Brain Uptake of LAT1-Targeted Amino Acid Prodrugs of Dopamine

Purpose

Drug delivery to the brain is impeded by the blood-brain barrier (BBB). Here, we attempted to enhance the brain uptake of cationic dopamine by utilizing the large amino acid transporter 1 (LAT1) at the BBB by prodrug approach.

Methods

Three amino acid prodrugs of dopamine were synthesized and their prodrug properties were examined in vitro. Their LAT1-binding and BBB-permeation were studied using the in situ rat brain perfusion technique. The brain uptake after intravenous administration and the dopamine-releasing ability in the rat striatum after intraperitoneal administration were also determined for the most promising prodrug.

Results

All prodrugs underwent adequate cleavage in rat tissue homogenates. The prodrug with phenylalanine derivative as the promoiety had both higher affinity for LAT1 and better brain uptake properties than those with an alkyl amino acid -mimicking promoiety. The phenylalanine prodrug was taken up into the brain after intravenous injection but after intraperitoneal injection the prodrug did not elevate striatal dopamine concentrations above those achieved by corresponding L-dopa treatment.

Conclusions

These results indicate that attachment of phenylalanine to a cationic drug via an amide bond from the meta-position of its aromatic ring could be highly applicable in prodrug design for LAT1-mediated CNS-delivery of not only anionic but also cationic polar drugs.