[Biomechanics of implant retained fixed prosthesis in patient with edentulous upper jaw]. / Biomekhanika nes''emnogo proteza na implantatakh pri polnom otsutstvii zubov na verkhnei cheliusti.

The purpose of the study was to study the stress-strain state of bone tissue and a permanent prosthesis on implants installed in the frontal part of the upper jaw. The 150N load was applied to the frontal and 250N to the side of the non-removable prosthesis on six or four implants, including zygomatic and 'All-On-Four' technology. The values of stresses in bone tissue, implants and prosthesis are obtained, which show a large margin of strength in structural materials. At the same time, the bone strength is low, especially around the zygomatic implants and the extreme implants 'All-on-4' with the load of the lateral part of the prosthesis.

Increased frequency of alleles associated with elevated tumor necrosis factor-alpha levels in children with Kawasaki disease.

Genetic polymorphisms influence the magnitude of the cytokine response after an inflammatory stimulus. To determine whether such polymorphisms might play a role in Kawasaki disease (KD), we analyzed white and Japanese children with KD and control populations for two polymorphic loci in which the A allele is associated with high tumor necrosis factor-alpha secretion. The lymphotoxin-alpha+250 A/A genotype was overrepresented among white children with KD compared with controls (0.59 versus 0.36; p = 0.013). The tumor necrosis factor-alpha-308 A/G genotype was overrepresented among whites with KD who had coronary artery abnormalities compared with those with normal echocardiograms (0.36 versus 0.09; p = 0.044). No significant difference was seen at either locus between Japanese children with KD and Japanese controls. The increased frequency of the high secretor alleles in white children with KD suggests that these loci may be related to susceptibility to KD and to outcome after disease.

Relationship of climate, ethnicity and socioeconomic status to Kawasaki disease in San Diego County, 1994 through 1998.

BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired heart disease in children in the United States. By monitoring trends in patient numbers and demographics during a 5-year period, we were able to explore the relationship between climate, ethnicity, socioeconomic status and susceptibility to KD. METHODS: We conducted active surveillance for all patients hospitalized with KD in San Diego County from 1994 through 1998. Data on seasonal variation in monthly rainfall and temperature were obtained from the US Meteorological Service. Patient sex, age, date of admission and self-reported ethnicity were identified from patient medical records. Socioeconomic status was assessed on the basis of insurance status among patients hospitalized at a single institution. RESULTS: During the 5-year period there were 169 cases of KD in San Diego County. The overall annual incidence of KD in children < 5 years of age ranged from 8.0 to 15.4/100 000. KD incidence was inversely associated with average monthly temperature (r = -0.47, P < 0.001) and positively associated with average monthly precipitation (r = -0.52, P < 0.001). Asian/Pacific Islanders < 5 years of age were 2.7 times as likely and Hispanics were one-third as likely to be hospitalized for KD than children from all other ethnic groups combined. Children with private or military insurance in all ethnic groups were more likely to have a diagnosis of KD than children with government assistance or no insurance. After controlling for insurance status, only Asian/Pacific Islanders remained at increased risk (rate ratio, 2.14) for KD relative to all other ethnic groups combined. CONCLUSION: KD is a common childhood vasculitis of unknown etiology. The skewed ethnic distribution and seasonality are consistent with the hypothesis that KD is an infectious disease that is influenced by environmental and genetic factors.

Passive surveillance for Kawasaki disease in San Diego County.

BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired heart disease in children in the United States. Epidemiologic surveillance is conducted to monitor baseline incidence of the disease and to identify epidemics. The aim of this study was to evaluate a passive surveillance system for reporting cases of KD in San Diego County to the local, state and national health authorities. METHODS: We performed a retrospective review of a 2-year period to identify the number of patients who met criteria of the Centers for Disease Control and Prevention for diagnosis of KD and who were successfully reported to the county, state and national databases. RESULTS: The total number of KD patients for 1994 and 1995 was determined by retrospective review of medical record discharge diagnosis codes. Of the 28 San Diego County residents diagnosed with KD in 1994, 24 (86%) met CDC criteria and 15 (63%) of these eligible patients were reported to the county and state health authorities. Of the 41 residents in 1995, 34 (83%) met CDC criteria and 22 (65%) were reported to the above agencies. No patient in either 1994 or 1995 was reported by local or state health authorities to the CDC. CONCLUSION: Passive surveillance for KD in San Diego County resulted in the reporting of approximately two-thirds of the eligible patients at the county and state levels but completely failed to report any documented cases to the CDC. Implementation of a sentinel hospital reporting system should be considered as a preferred alternative to national passive surveillance in the effort to track total numbers of patients and to follow disease trends over time.

In situ hybridization histochemical localization of prodynorphin messenger RNA in the central nervous system of the rat.

The distribution of preprodynorphin messenger RNA-containing perikarya in the central nervous system of the rat was determined with in situ hybridization histochemistry using a 35S-labelled complementary RNA probe. All of the regions of the central nervous system reported by other investigators to contain perikarya that synthesize prodynorphin-derived peptides, except the pedunculopontine tegmental nucleus, the accessory trigeminal nucleus, and the ventral nucleus of the trapezoid body, also contained perikarya that synthesize preprodynorphin messenger RNA. However, the olfactory bulb, the anterior olfactory nucleus, the islands of Calleja, the CA1-CA3 fields of the hippocampus, the septohippocampal nucleus, the diagonal band of Broca, the basal and cortical amygdaloid nuclei, the entopeduncular nucleus, the subthalamic nucleus, the superior colliculus, the Edinger-Westphal nucleus, the dentate nucleus, the raphes linearis and pontis, the dorsal cochlear nucleus, the medial vestibular nucleus, the inferior olive, and the dorsal motor nucleus of the vagus nerve also contained preprodynorphin messenger RNA-synthesizing perikarya. These observations suggest that prodynorphin-derived peptides have a much more pervasive role in central nervous system function than previously suspected. However, before the physiological significance of these observations can be judged, it will be necessary to determine whether all of the novel sites of preprodynorphin messenger RNA synthesis are sites of prohormone synthesis and conventional processing.

Dextromethorphan blocks opioid peptide gene expression in the rat hippocampus induced by kainic acid.

We have previously shown that dextromethorphan (DM) antagonizes kainic acid (KA)-induced neurotoxicity. Accumulating evidence indicates that the induction of seizure activity causes profound alterations in the levels of hippocampal opioid peptide mRNA. The present study was performed to further explore the effect of DM on KA-induced seizures as measured by hippocampal opioid peptide mRNA levels. Both Northern blot and in situ hybridization methods were used to examine the proenkephalin (PENK) and prodynorphin (PDYN) mRNA levels in the rat hippocampus. The robust seizure activity induced by KA correlated with a significant increase in hippocampal opioid peptide mRNA levels. Pretreatment of rats with DM decreased hippocampal PENK and PDYN mRNA levels and seizure activity induced by KA. Hippocampal PDYN mRNA levels fell quickly but PENK mRNA levels fell rather slowly, indicating that the PENK and PDYN mRNAs are differentially regulated. Our results demonstrate that DM modulates opioid peptide gene expression induced by KA, and that DM protects against KA-induced seizures.

Methamphetamine-induced changes in AP-1 binding and dynorphin in the striatum: correlated, not causally related events?

Activation of D1 dopamine (DA) receptors in the striatum increases the expression of the opioid neuropeptide, dynorphin (DYN). While cAMP is generally accepted as a second messenger in this signal transduction pathway, the role of Fos/FRA proteins and AP-1 binding in mediating D1 receptor-induced changes in DYN expression remains uncertain. In this study, DYN peptide and mRNA levels, as well as Fos/FRA proteins and AP-1 DNA binding activity, were measured in individual animals following acute challenge with the psychostimulant drug methamphetamine (METH). METH caused an initial decrease in striatal levels of DYN A, reflecting increased peptide release. Six hours postinjection, DYN mRNA levels were significantly elevated by METH as compared to vehicle-injected controls. At the same time, these drugs increased the expression of Fos/FRA-ir proteins, in particular the 35- and 40-kDa molecular weight species, and increased binding to the AP-1 DNA element. Analyses of the time course of METH's effects revealed that DYN mRNA levels, Fos/FRA proteins and AP-1 binding activity showed variable increases by 3 h but all were significantly elevated above control levels by 6 h posttreatment. The D1-specific antagonist, SCH 23390, completely blocked the METH-induced changes in DYN peptide and mRNA levels while a D2 receptor antagonist (sulpiride) had little or no effect. These data indicate that stimulant drugs such as METH increase the expression of DYN and AP-1 factors in the striatum via a D1 receptor-mediated mechanism. However, the finding that AP-1 binding merely paralleled, but did not precede, the increase in DYN expression, as would be expected if it were mediating increased gene transcription, suggests these may be correlative, not causally related events.

The effects of dextromethorphan on kainic acid-induced seizures in the rat.

Several studies have shown that dextromethorphan (DM) has both anticonvulsant and proconvulsant effects depending on the animal model. In this study, we examined the effects of DM on three parameters associated with kainic acid (KA)-induced seizures: cell loss in the hippocampus, increased AP-1 DNA binding activity and increased c-Jun and fos-related antigen (FRA) expression. KA administration (8 mg/kg, ip) produced robust behavioral convulsions lasting 4-6 hr. Pretreatment with DM (12.5-75 mg/kg, po) 15 min before KA injections reduced the seizures as well as mortality in a dose-dependent manner. Histological studies revealed a severe loss of cells in the CA1 and CA3 fields of the hippocampus in KA-treated rats. DM pretreatment also reduced this cell loss in a dose-dependent fashion. Biochemical studies showed that DM pretreatment also attenuated the KA-induced increase of AP-1 binding activity and c-Jun/FRA expression in the hippocampus. These results indicate that DM is an effective antagonist of KA.

Glia-dependent neurotoxicity and neuroprotection in mesencephalic cultures.

Dopaminergic neurotoxicities of 6-hydroxydopamine (6-OHDA) and the lipopolysaccharide (LPS) were compared in rat mesencephalic cultures plated on poly-L-lysine or on glial monolayers. In the neuron-enriched cultures plated on polylysine, 6-OHDA killed 89% of the tyrosine hydroxylase (TH)-immunopositive neurons, but LPS was not neurotoxic. Conversely, in mixed neuron/glial cultures, 6-OHDA killed only 27% of the TH-immunopositive neurons while LPS killed 70%. The mixed neuronal/glial mesencephalic culture offers a better in vitro model for studying possible mechanisms involved in Parkinson's disease.

Effects of chronic opiate and opioid antagonist treatment on striatal opioid peptides.

It has long been speculated that feedback inhibition of endogenous opioid neurons may have a role in opiate tolerance and dependence. However, in studies in which opiates or opioid antagonists have been administered to animals, mixed results have been obtained on the ability of these drugs to regulate endogenous opioids. The present studies were undertaken to determine the effects of chronic administration of opiate drugs on opioid peptides. These studies focused on the regulation of prodynorphin (Prodyn) and proenkephalin (Proenk) peptides in striatal tissue. Morphine, whether administered by chronic infusion or repeated injection, was found to increase the concentration of Prodyn peptides in striatum. Increases were statistically significant in the sensorimotor dorsal striatum (caudate-putamen) but not in the limbic-motor ventral striatum (nucleus accumbens-olfactory tubercle). No changes in Prodyn peptides were found following chronic administration of the opioid antagonist naltrexone. No changes in the Proenk peptide MERGL were found following chronic treatment with morphine or naltrexone. These studies are consistent with the suggestion that Prodyn neurons may have a role in the consequences of long-term opiate administration.

Effects of sulpiride and SCH 23390 on methamphetamine-induced changes in body temperature and lethality.

Data from human and animal studies suggest that hyperpyrexia contributes to both the neurotoxic and the lethal effects of stimulant drugs such as methamphetamine (METH). Because many of the effects of METH involve the release of dopamine from CNS neurons, we examined the effects of D1 and D2 dopamine receptor antagonists on METH-induced lethality and determined whether these effects correlated with changes in body temperature. In the first set of experiments, we found that the D2 antagonist sulpiride (SUL; 20, 40 or 80 mg/kg) potentiated the lethality caused by a single injection of METH (10 mg/kg). Pretreatment with the D1 antagonist SCH 23390 (SCH; 0.5 mg/kg) reduced the lethality induced by METH alone or by SUL/METH. Other D2 or 5-hydroxytryptamine antagonists prevented, rather than potentiated, METH-induced lethality. In a second set of experiments, rectal temperatures were recorded in METH-injected animals pretreated with SCH or SUL. METH caused a significant increase (i.e., above vehicle-injected levels) in body temperature at 2.5 hr after injection. The effects of SCH or SUL pretreatment on METH-induced changes in body temperature suggest that the lethality-potentiating and -protective effects of SUL and SCH, respectively, were not due to altered thermoregulatory responses. These data support the idea that D1 receptor activation is an important event in the lethality caused by METH and that SUL may potentiate D1 receptor activation by augmenting METH-induced DA release.

Induction of proenkephalin in tuberoinfundibular dopaminergic neurons by hyperprolactinemia: the role of sex steroids.

The observation that tuberoinfundibular dopaminergic (TIDA) neurons of pregnant, pseudopregnant, lactating, and aged rats express enkephalins suggested that chronically elevated PRL levels, which are characteristic for these animals, are essential for the induction of proenkephalin gene expression in TIDA neurons. The present studies investigated further the role of PRL in this phenomenon. Elevated PRL levels were achieved either experimentally by implanting anterior pituitaries under the kidney capsule of intact or hypophysectomized female rats or by using lactating rats. For controls, the elevated PRL levels were reduced with bromocryptine, a dopamine receptor agonist. The role of sex steroids in PRL-induced enkephalin gene expression was also studied in cycling, sex hormone-treated, hypophysectomized or ovariectomized rats, pituitary-implanted/sex hormone-treated rats, and ovariectomized mothers. Enkephalin immunoreactivity was detected by immunocytochemistry and enkephalin messenger RNA with in situ hybridization histochemistry using 35S- or digoxigenin-labeled riboprobes. Enkephalin or its messenger RNA was present in TIDA neurons in all experimental animals with elevated PRL levels. Although estradiol had no or only a minor effect on PRL-induced enkephalin gene expression, progesterone supported the effect of PRL. The present observations suggest that the expression of enkephalin in TIDA neurons is PRL dependent and supported by sex steroids, primarily progesterone.

Role of a 35 kDa fos-related antigen (FRA) in the long-term induction of striatal dynorphin expression in the 6-hydroxydopamine lesioned rat.

D1 dopamine (DA) receptor agonists induce the expression of the opioid peptide dynorphin (DYN) in the striatum, an effect accentuated several fold by removing the dopaminergic innervation to the striatum (e.g., by lesioning the DA cell bodies in the substantia nigra [SN]). D1 receptor-mediated effects are thought to involve cAMP and/or phosphoinositides as second messengers. However, it is unclear what third messengers are involved in the regulation of DYN expression. The present experiments evaluated the possible role of two families of immediate-early gene (IEG) proteins, Fos and Jun, in the induction of DYN biosynthesis following repeated treatment with DA agonists. In addition, the role of N-methyl-D-aspartate (NMDA) receptors in modulating DA-induced changes in DYN and IEG protein expression was assessed. Adult male rats received unilateral 6-hydroxydopamine (6-OHDA) or sham lesions of the SN. Following a recovery period, animals were injected twice daily with the DA agonist, apomorphine (APO; 5 mg/kg), for 4 or 7 days. As expected, APO induced DYN biosynthesis, at both the peptide and mRNA level, several fold more in the striatum ipsilateral to the 6-OHDA lesion than in the contralateral control side (or a sham lesioned striatum). These effects appeared to be mediated by D1 receptors since the D1 agonist, SKF 38393 (5 mg/kg), caused the same changes in DYN expression as APO whereas a D2 agonist, quinpirole (1 mg/kg), had no effect. Paralleling the increase in DYN expression, APO also induced the expression of c-Fos and Fos-related antigens (FRA's), in particular a 35 kDa FRA, but had no effect on the expression of various Jun-related IEG proteins (i.e., c-Jun, Jun B, Jun D). Consistent with the notion that Fos and FRA proteins alter transcriptional activity by binding to AP-1 (or AP-1-like) DNA sequences in the promoter regions of target genes, we found that repeated APO treatment caused large increases in AP-1 binding activity in striata ipsilateral to 6-OHDA lesions. These data indicate that repeated activation of D1 receptors increases both the expression of a 35 kDa FRA and AP-1 binding, events which may mediate the large increases in DYN expression in the DA denervated striatum. While co-administration of the NMDA receptor antagonist, MK-801, inhibited APO-induced increases in DYN and Fos/FRA expression in the intact striatum, its only effect in the DA-denervated striatum was a partial (35%) inhibition of the APO-induced increase in DYN-ir concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Dopamine regulation of swim stress induction of the pituitary intermediate lobe proopiomelanocortin system.

Previous studies have indicated that 30 min of swimming in room temperature water is a potent stimulus for the secretion of beta-endorphin (beta E) from the intermediate lobe (IL) of the pituitary in rodents. Repeated daily challenge with this paradigm over days to weeks leads to a progressive increase in proopiomelanocortin (POMC)-derived IL peptides and POMC mRNA levels as well as an increase in the stimulated secretion of beta E in response to rechallenge with swim. The current studies were undertaken to examine the possible role of dopamine systems in mediating swim stress-induced changes in IL beta E biosynthesis and release. Confirming previous results, a 30 min swim stress exposure caused plasma concentrations of beta E to increase several fold. Apomorphine (APO), a dopaminergic agonist, completely blocked this effect, suggesting that dopamine receptors may mediate the acute IL response to swim stress. Animals that swam once daily for 14 days displayed elevated beta E levels in both the IL and plasma 24 h after the last swim session. In these animals, repeated administration of APO did not reverse swim-stress-induced changes in beta E. Immediately following an acute-swim rechallenge, animals which had been previously swim-stressed for 14 days demonstrated significantly greater beta E release than naive animals. Again, an acute injection of APO inhibited the acute increase in IL secretion, suggesting that repeatedly swum animals are still responsive to the acute effects of APO even though repeated coadministration of APO with swim exposure had no effect on IL beta E peptide stores or plasma beta E concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of chronic morphine treatment on beta-endorphin-related peptides in the caudal medulla and spinal cord.

The effects of chronic morphine treatment on beta-endorphin (beta E)-immunoreactive (beta E-ir) peptide levels were determined in the rat caudal medulla and different areas of the spinal cord. Seven days of morphine pelleting had no effect on total beta E-ir peptides in the caudal medulla. In contrast, it significantly increased beta E-ir peptide concentrations in the cervical and thoracic regions of the spinal cord compared with placebo-pelleted controls, whereas in the lumbosacral region this trend did not reach statistical significance. Injections of the opiate receptor antagonist naloxone 1 h before the rats were killed had no effect on the morphine-induced increases in the cord. Chromatographic analyses revealed that enzymatic processing of beta E-related peptides in the spinal cord seemed unaffected by the morphine and/or naloxone treatments. In light of previous data showing that morphine down-regulates beta E biosynthesis in the hypothalamus, the present results suggest that the regulation of beta E-ir peptides in the spinal cord is distinct from that found in other CNS areas. These data provide support for previous results suggesting that beta E-expressing neurons may be intrinsic to the spinal cord.

Pre- and posttranslational regulation of beta-endorphin biosynthesis in the CNS: effects of chronic naltrexone treatment.

There appear to be two anatomically distinct beta-endorphin (beta E) pathways in the brain, the major one originating in the arcuate nucleus of the hypothalamus and a smaller one in the area of the nucleus tractus solitarius (NTS) of the caudal medulla. Previous studies have shown that these two proopiomelanocortin (POMC) systems may be differentially regulated by chronic morphine treatment, with arcuate cells down-regulated and NTS cells unaffected. In the present experiments, we examined the effects of chronic opiate antagonist treatment on beta E biosynthesis across different CNS regions to assess whether the arcuate POMC system would be regulated in the opposite direction to that seen after opiate agonist treatment and to determine whether different beta E-containing areas might be differentially regulated. Male adult rats were administered naltrexone (NTX) by various routes for 8 days (subcutaneous pellets, osmotic minipumps, or repeated intraperitoneal injections). Brain and spinal cord regions were assayed for total beta E-ir, different molecular weight immunoreactive beta-endorphin (beta E-ir) peptides, and POMC mRNA. Chronic NTX treatment, regardless of the route of administration, reduced total beta E-ir concentrations by 30-40% in diencephalic areas (the arcuate nucleus, the remaining hypothalamus, and the thalamus) and the midbrain, but had no effect on beta E-ir in the NTS or any region of the spinal cord. At the same time, NTX pelleting increased POMC mRNA levels in the arcuate to approximately 140% of control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of azole compounds for the treatment of experimental aspergillosis in turkeys.

A model for aspergillosis by injecting fungal spores into the lung is described. The model permits evaluation of anti-mycotic agents and their effect on the development of lesions in the infected lung, the spreading to the second lung and other organs. The therapeutic effect of the azole compounds enilconazole, ketoconazole, itraconazole and levamisole was determined. Itraconazole was found to be the most effective.

Evidence that beta-endorphin is synthesized in cells in the nucleus tractus solitarius: detection of POMC mRNA.

Evidence from a number of sources indicates that the major site of pro-opiomelanocortin (POMC)-producing cells in the CNS is the arcuate nucleus of the hypothalamus. Using immunocytochemical techniques, a second, smaller group of POMC cells has been detected in the nucleus tractus solitarius (NTS) area of the caudal medulla. However, POMC mRNA has never been reported in the NTS even though it has been found in other extrahypothalamic brain regions. Thus, there is some uncertainty as to whether POMC peptides are actually synthesized de novo in the NTS. In the present study, we used biochemical and anatomical techniques to examine whether POMC mRNA is localized in the NTS. Using in situ hybridization, cells containing POMC mRNA were found in the caudal portion of the NTS. The nucleic acid distribution correlated well with the anatomical distribution of 16k POMC peptide immunoreactivity as determined by immunocytochemistry. Northern analysis revealed that the apparent size of POMC mRNA in the NTS was similar to that found in the arcuate nucleus or the pituitary gland. Results of RNase protection assays using a POMC riboprobe complementary to the 5' end of exon 3 suggested that POMC mRNA in the NTS and arcuate nucleus are identical in this region of the message at least. We also calculated POMC peptide product to mRNA ratios in different tissues and found that NTS cells appear to produce less peptide per mRNA molecule than those in the arcuate nucleus or pituitary gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of morphine treatment on pro-opiomelanocortin systems in rat brain.

In previous studies to determine whether chronic opiate administration might negatively feedback upon endogenous opioid systems in the CNS, investigators found no changes in steady-state concentrations of opioid peptides following morphine pelleting. However, since only steady-state levels were measured, it was still not clear whether morphine treatment altered the release and/or biosynthesis of opioid-containing neurons. The goal of the present study was to assess the effects of chronic morphine pelleting on the dynamics of beta-endorphin (beta E) biosynthesis in rats. Hence, at several times during a 7-day morphine treatment, concentrations of total beta E-immunoreactivity (-ir), as well as chromatographically sieved forms of beta E, were determined by RIA, and mRNA levels of pro-opiomelanocortin (POMC) were measured by a solution phase protection assay using a mouse or rat POMC 32P-labelled riboprobe. Concentrations of total beta E-ir or different forms of beta E-ir peptides (i.e. beta-lipotropin, beta E1-31, or beta E1-27/beta E1-26) in the hypothalamus or midbrain following either 1 or 7 days of treatment were similar in morphine- and placebo-pelleted animals. However, a significant increase in total hypothalamic beta E-ir was observed following 3 days of morphine pelleting; chromatographic analyses indicated that this was primarily due to a selective increase in the opiate inactive forms of beta E, i.e. beta E1-27/beta E1-26. After 7 days of pelleting, morphine-treated animals tended to have lower POMC mRNA levels than those of placebo controls (20 to 50% decrease in different studies). The accumulation of hypothalamic beta E-ir at 3 days, and the apparent decline in POMC mRNA levels at 7 days, lend support to the hypothesis that morphine negatively feeds back upon POMC neurons in the brain by inhibiting beta E release and biosynthesis.