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The southern oscillation index (SOI) is a characteristic of the El Niño phenomenon. SOI monthly averaged data is analyzed for the time interval 1866-2000. The tail of the cumulative distribution of the fluctuations of SOI signal is studied in order to characterize the amplitude scaling of the fluctuations and the occurrence of extreme events. Large fluctuations are more likely to occur than the Gaussian distribution would predict. The time scaling of fluctuations is studied by applying the energy spectrum and the detrended fluctuation analysis statistical method. Self-affine properties are found to be pertinent to the SOI signal and therefore suggest power-law correlations of fluctuations of the signal. An antipersistent type of correlations exists for a time interval ranging from about 4 months to about 6 years. This leads to favoring specific physical models for El Niño description.

Nitric oxide (NO) is a reactive endogenous molecule with multiple functions and its cellular signaling activity is mainly mediated by activation of the soluble isoform of guanylyl cyclase, a heterodimeric (alpha/beta) hemeprotein. The expression of the NO-sensitive soluble isoform of guanylyl cyclase was studied in various cultured melanocytic cells by measuring the accumulation of guanosine 3',5'-cyclic monophosphate in the presence and absence of NO donors. Here we report that 3-morpholino-sydnonimine, a donor of NO redox species, and (Z)-1-[2- (2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, a direct NO donor, induced a 20-fold increase in intracellular guanosine 3',5'-cyclic monophosphate in nonmetastatic melanoma cells and normal melanocytes in culture that could be related to cellular melanin content in a concentration-dependent manner. The increased intracellular guanosine 3',5'-cyclic monophosphate was due to stimulation of the activity of soluble guanylyl cyclase as such increase was completely abolished by using a specific inhibitor of soluble guanylyl cyclase. The involvement of functional soluble guanylyl cyclase was further confirmed by the presence of alpha1 and beta1 subunits in these cells at both mRNA and protein levels. In contrast, none of the NO donors induced guanosine 3',5'-cyclic monophosphate production in metastatic melanoma cells, which could be attributed to the absence of the beta1 subunit that is essential for catalytic activity of the soluble isoform of guanylyl cyclase. Metastatic melanoma cells produced higher levels of intracellular guanosine 3',5'-cyclic monophosphate in response to natriuretic peptides than other cell types, however, due to upregulation of membrane-bound guanylyl cyclase activities, but they are less pigmented or unpigmented. The present finding suggests that NO signaling in association with melanogenesis is dependent on the soluble isoform of guanylyl cyclase, whereas absence of soluble guanylyl cyclase but the presence of membrane-bound guanylyl cyclase correlates with the metastatic behavior of melanoma cells.

The incidence of dental caries /Is/ on deciduous molars in 1216 children aged 3 to 8 from Plovdiv has been studied. The results showed highest Is in the fissures of m1 and m2 and lowest Is on the smooth surfaces. The incidence of dental caries is getting higher with statistically significant differences in the lower jaw up to the 6th year and in the upper jaw up to 7th year of age. Is in the lower jaw is higher than that of the upper jaw only in the fissures.

The specification of the occlusal contacts in the posterior teeth region is a necessary clinical reference point for creating optimal interrelations between the teeth and dentition. The methods, such as the photo-occlusal method, the quasiplanimetric method, two-phase proof imprint in central occlusion, recording of contacts with profile wax, that have been used in studying the number and location of occlusal contacts at various positions of the mandible in relation to the maxilla are exact but difficult to apply clinically. The purpose of the present study is to find the topographic distribution of occlusal contacts in intact first mandibular molars using a method that is easy to utilise clinically and to compare the present results with the findings of the authors. The masticatory teeth of 100 high-school students (18 years old) without subjective complaints or objective structural or functional disorders of the temporomandibular joint were studied by means of articulation paper. From that sample 41 students with intact dentition and orthognathic occlusion were selected. The first mandibular molars (N = 77) were studied. The results are as follows. The occlusal contacts in the first mandibular molar vary from 1 to 7. The greatest percentage of contacts is observed in the tubercles. In the first mandibular molar the biting pressure upon the tubercle apex areas is greater compared to that on the sloping areas. Our results were compared with the findings obtained by the other three methods mentioned above. Our method allows objective specification of the topographic distribution of occlusal contacts.

The aim of the investigation was to clarify, whether cellular signal processing following graviperception involves second messenger pathways. The test object was a most gravisensitive free-living ameboid cell, the myxomycete (acellular slime mold) Physarum polycephalum. It was demonstrated that the motor response is related to acceleration-dependent changes in the levels of the cellular second messenger cyclic adenosine monophosphate (cAMP). Rotating Physarum plasmodia in the gravity field of the Earth about a horizontal axis increased their cAMP concentration. Depriving the cells for a few days of the acceleration stimulus (near weightlessness in a space experiment on STS-69) slightly lowered plasmodial cAMP levels. Thus, the results provide first indications that the acceleration-stimulus signal transduction chain of Physarum uses an ubiquitous second messenger pathway.

Gravitactic protozoa offer advantages in studying how the gravity stimulus is perceived on the cellular level. By means of a slow rotating centrifuge microscope in space the acceleration thresholds for gravitaxis of Loxodes striatus and Paramecium biaurelia were determined: < or = 0.15 x g for Loxodes and 0.3 x g for Paramecium, indicating different sensitivities of these species. Neutral-buoyant densities of immobilized cells were determined using media of different densities, revealing densities of 1.03 to 1.035 g/cm3 for Loxodes and 1.04 g/cm3 to 1.045 g/cm3 for Paramecium. Behavioral studies revealed that gravitaxis of Loxodes persisted independent of the density of the medium. In contrast, negative gravitaxis of Paramecium was no longer measurable if the density of the medium approached the density of the cell. The results suggest that in the case of Loxodes gravity is perceived by an intracellular receptor and, in the case of Paramecium by its own mass via the pressure on the lower cell membrane.

The aim of the present study was to explore whether nitric oxide (NO) interferes with the attachment of human melanocytes to the extracellular matrix (ECM) components. Consequently, the effects have been investigated of the NO-releasing compounds 3-morpholino-sydnonimine (SIN-1) and S-nitroso-glutathione (GSNO) on the in vitro adhesion of human melanocytic cells to fibronectin. The NO donors induced a concentration-dependent reduction in the adhesion of both 51CrO4(2-)-labelled melanocytes and melanoma cells to fibronectin. Pigmented M14 melanoma cells were more susceptible to the effect of SIN-1 (half-maximal inhibiting effect at about 0.5 mM) than normal human melanocytes and also than the non-pigmented melanoma cells Mel57 (half-maximal inhibiting effects between 0.9 and 2 mM). This effect of SIN-1 also appeared to be related to the melanin content of normal melanocytes, whereas GSNO was significantly less active. Both flow cytometric analysis and immunocytochemical staining showed expression of neuronal NO synthase in all cell lines. The results of this study suggest that aberrant in vivo production of NO during infection and inflammation may contribute to loss of melanocytes in, for example, vitiligo, by reducing de novo attachment of melanocytes to the ECM. These findings could also be important for understanding the process of metastasis.

A case of a patient with a 20-year history of chronic otitis media complicated by cholesteatoma and brain abscess is described. A CT scan with contrast material showed three abscess cavities in the right cerebellar hemisphere. A culture from a specimen of the cholesteatoma yielded a significant amount of growth of Bilophila wadsworthia, Bacteroides fragilis and Prevotella oris and a moderate growth of alpha-streptococci and Staphylococcus simulans. From the pus of the brain abscess we also isolated numerous Bilophila wadsworthia, Bacteroides fragilis and Prevotella oris and some Prevotella buccae and Peptostreptococcus anaerobius. No aerobes were present. The patient underwent a craniotomy and the biggest abscess was removed together with the capsule. The antimicrobial therapy included penicillin plus metronidazole and later augmentin. The result of the treatment was a complete cure and total recovery of the patient. This is the first documentation of isolation of B. wadsworthia in chronic otitis media and in brain abscess.

Cellular signal processing in multi-, as well as in unicellular organisms, has to rely on fundamentally similar mechanisms. Free-living single cells often use the gravity vector for their spatial orientation (gravitaxis) and show distinct gravisensitivities. In this investigation the gravisensitive giant ameboid cell Physarum polycephalum (Myxomycetes, acellular slime molds) is used. Its gravitaxis and the modulation of its intrinsic rhythmic contraction activity by gravity was demonstrated in 180 degrees-turn experiments and in simulated, as well as in actual, near-weightlessness studies (fast-rotating clinostat; Spacelab D1, IML-1). The stimulus perception was addressed in an IML-2 experiment, which provided information on the gravireceptor itself by the determination of the cell's acceleration-sensitivity threshold. Ground-based experiments designed to elucidate the subsequent steps in signal transduction leading to a motor response, suggest that an acceleration stimulus induces changes in the level of second messenger, adenosine 3',5'-cyclic monophosphate (cAMP), indicating also that the acceleration-stimulus signal transduction chain of Physarum uses an ubiquitous second messenger pathway.

Objectives: The aim of the present study was to investigate the effects of a community-based milk fluoridation project on dental caries., Methods: Fluoridated milk was provided to about one-half of kindergarten and other schoolchildren in Asenovgrad, a town in the southern part of Bulgaria. The estimated daily milk consumption was 200 ml containing 1 mg of fluoride (approximately 5 ppm F). Cross-sectional samples of 6 1/2-year-olds in Asenovgrad and Panaguriche (a nearby town selected as the reference community) were examined at the start of the study in 1988 and after three years. Additional cross-sectional samples of 7 1/2-year-olds in Asenovgrad who were and were not drinking fluoridated milk were examined at baseline and at three years to provided an internal control group. Samples of 6 1/2 and 8 1/2-year-olds from Asenovgrad and Karlovo were examined in 1993 to provide for five-year follow-up comparisons., Results: In 6 1/2-year-old children who had consumed fluoridated milk for three years, there was a decrease in the mean dmft per child of 40 percent and in the mean DMFT of 89 percent compared to children examined at baseline. Children in Asenovgrad who were 4 1/2 years old at the start of the study and had been drinking fluoridated milk for three years had on average 44 percent fewer dmft and 83 percent fewer DMFT at 7 1/2 years of age than those not drinking fluoridated milk. After five years the dmft index was 40 percent less and the DMFT index 79 percent less in those children who had participated in the full five years of the program compared to the control group., Conclusions: Results seem to confirm the caries-reducing effects of milk fluoridation found in previous studies. Unexpected large caries reductions obtained in this nonexperimental study, however, probably cannot be attributed to the fluoridation of milk alone. The mere introduction of the project might have led to other changes affecting dental caries, such as improved oral hygiene and better dietary habits.

The aim of the present study has been to investigate the caries-reducing effect of a community-based milk fluoridation project. In those Kindergartens where fluoridated milk had been delivered on a regular basis, the estimated consumption corresponded to a daily intake of 200 mL milk containing 1 mg F- (5 ppm F-) for periods of 180-200 days per year. A total of 204 six-year-old children, randomly selected, was examined at baseline and three and a half years after the start of the project. A statistically significant reduction in the prevalence of dental caries was obtained for those children who had received fluoridated milk on a regular basis. In six-year-old children, the reduction in the dmft figure was 40% and in the DMFT figure, 90%. Despite the deficiencies in the design of this study (dictated by local circumstances), the results confirm the findings of other studies on the caries-reducing effect of fluoridated milk. The results also confirm that the earlier in the child's life the consumption of fluoridated milk starts, the better the effect.

The present study was undertaken to compare inhibitory effects of the cGMP analog 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (8-PCPT-cGMP) on increases in cytosolic ionized Ca2+ and on aggregation in human platelets induced via diverse agonists. Fura-2-loaded and gel-filtered platelets were stimulated by either ADP (8 microM), thrombin (0.025 IU/ml) or collagen (1-3 micrograms/ml), respectively. The cGMP analog induced a concentration-dependent inhibition of cytosolic ionized Ca2+ increases and of aggregation to all agonists investigated with half-maximal inhibiting effects of approximately 100 microM. The data obtained suggest that both platelet Ca2+ exchange and aggregation have a similar sensitivity to the cGMP analog. In accordance with previously found significant differences between the potencies of nitric oxide (NO)-generating substances to inhibit increases in cytosolic ionized Ca2+ and aggregation, it appears that the antiplatelet effects of NO-releasing agents could only partially be explained by the elevation of cGMP levels.

The present study was undertaken to determine the modulatory effects of nitric oxide (NO)-releasing compounds on increases in cytosolic ionized calcium ([Ca2+]i) and on aggregation of gel-filtered human platelets induced via diverse agonists. We used various sydnonimines and organic nitrates as donors of NO. Gel-filtered and fura-2-loaded platelets were stimulated with ADP (4-8 microM), collagen (2-10 micrograms/ml) or thrombin (0.02-0.05 IU/ml), respectively. Half-maximal inhibiting effects of sydnonimines on agonist-evoked increases in [Ca2+]i were observed between 30 and 1000 nM, while half-maximal inhibiting effects of the compounds on aggregation were between 3 and 500 nM. The compound C 87-3754, which is the bioactive metabolite of pirsidomine, was a much stronger inhibitor of increases in [Ca2+]i than of platelet aggregation. This was due to an enhanced NO release from this compound exposed to ultraviolet light during Ca2+ measurement. The organic nitrates isosorbide 5-mono-nitrate and nicorandil inhibited both aggregation and increase of cytosolic ionized calcium in stimulated platelets at half-maximal concentrations of approximately 200 microM. The present results suggest that some of the effects of NO on platelets are independent of cytosolic ionized calcium. The results also suggest that some of the inhibitory effects of NO-releasing compounds correspond rather to the presence of the A forms (NO-containing intermediates) than to the presence of free NO.

The present investigation describes kinetic characteristics of membrane-bound and Triton X-100-solubilized atrial natriuretic factor (ANF)-sensitive guanylate cyclase from bovine adrenal cortex. The kinetic analysis of both enzyme forms suggests that in the presence of manganese, ANF induces or stabilizes at least two apparent GTP*Mn2(+)- and in addition two Mn2(+)-binding sites. Addition of the natriuretic drug amiloride favors this state. ATP increases the vmax in the presence of ANF for GTP*Mg2+, but not for GTP*Mn2+ as a substrate. With GTP*Mg2+, amiloride has no effect on basal or ANF-stimulated activity, but slightly reduces the effect of ATP. Under all conditions tested, the enzyme follows regular Michaelis-Menten kinetics in the presence of Mg2+ and exhibits positive cooperativity with Mn2+. Positive cooperativity is also retained after Triton extraction. The results indicate that Triton extraction has no major influence on the kinetic properties of particulate guanylate cyclase when the extraction procedure is done carefully. The data also support the suggestion that multiple interactions of subunits might occur upon activation of the enzyme by ANF in the presence of Mn2+.

The natriuretic agent amiloride induces a shift of the dose-response curve of particulate guanylate cyclase to atrial natriuretic factor (ANF) to the left. The ANF concentration for half-maximal activation of guanylate cyclase is shifted from 20 to 3 nM in the presence of 100 microM amiloride. This effect is observed with GTP*Mn2+, but not with GTP*Mg2+ as substrate. Amiloride derivatives, which inhibit a specific Na+-channel, also shift the dose-response curve to the left. These data suggest that some of the effects of amiloride may be mediated by an increased sensitivity of particulate guanylate cyclase to ANF.

Fluorine content in natural cow milk has been determined with a view to the fluoration of the milk and its use for dental caries prophylaxis. Fluorine has been determined by the method of standard calibration, making use of fluorine selective electrode and "Orion SA 720 pH/ISE Meter" with LCD display. The mean fluorine quantity in milk is mean = 0.046 ppm, being far lower than the optimal fluorine concentration.