[The analysis of related factors on the unilateral aldosterone secretion in the functional diagnosis of primary aldosteronism and establishment of a predictive model].

Objective: To explore related factors associated with unilateral aldosterone secretion of patients with primary aldosteronism (PA) and construct a predictive model. Methods: The clinical data of patients who were diagnosed as PA in West China Hospital from April 2016 to September 2020 was analyzed retrospectively. According to the results of the adrenal enhancement CT, patients were divided into 3 groups, namely non-nodular group with no bilateral adrenal glands lesions, only with unilateral adrenal hyperplasia or bilateral adrenal hyperplasia, unilateral nodule group with unilateral adrenal nodules and the contralateral adrenal glands with hyperplasia or not, and bilateral nodules group with nodules in both adrenal glands. Regarding the related factors of dominant side of aldosterone secretion, univariate analysis and binary logistic regression were used. Receiver operating characteristic curve and nomogram were used to evaluate the diagnostic performance of regression models. Results: A total of 237 patients with PA were included, of which, 118 males and 119 females, the median age was 39 years, and the body mass index (BMI) was (25.2±3.5) kg/m2. There were 157 (66.2%) of 237 patients with typical imaging findings. There were 32 cases in no-nodular group, 183 cases in unilateral nodule group, and 22 cases in bilateral nodules group. Multivariate analysis showed that age (OR=0.876, P<0.001), blood potassium concentration (OR=0.430, P=0.004), and typical imaging findings (OR=2.202, P=0.035) were associated with unilateral aldosterone secretion. As for unilateral nodule group, multivariate analysis showed that age (OR=0.900, P<0.001), plasma aldosteronism concentration (PAC) (OR=1.050, P=0.018), and typical imaging findings (OR=2.637, P=0.025) were associated with unilateral aldosterone secretion. The agreement rate between the dominant side of the adrenal CT and AVS was only 50.2%. Multivariate analysis showed that age (OR=0.954, P=0.001), BMI (OR=0.893, P=0.024) and PAC (OR=1.043, P=0.011) were independently associated with concordance between AVS and CT. The cut-off value of the ROC curve was 0.43; the model sensitivity was 56.3%; the specificity was 86.7% and the area under the ROC curve was 0.742. Conclusions: Age is an important predictor in the diagnosis of PA subtypes. It is recommended to refer to subgroup based on imaging results for clinical decision. For patients with no obvious lesions or bilateral lesions on CT, AVS should be performed as far as possible to confirm the subtypes in diagnosis of PA.

Carboxylesterase expression in human dental pulp cells: role in regulation of BisGMA-induced prostanoid production and cytotoxicity.

Biocompatibility of dentin bonding agents (DBA) and composite resin may affect the treatment outcome (e.g., healthy pulp, pulpal inflammation, pulp necrosis) after operative restoration. Bisphenol-glycidyl methacrylate (BisGMA) is one of the major monomers present in DBA and resin. Prior studies focused on salivary esterase for metabolism and degradation of resin monomers clinically. This study found that human dental pulp cells expressed mainly carboxylesterase-2 (CES2) and smaller amounts of CES1A1 and CES3 isoforms. Exposure to BisGMA stimulated CES isoforms expression of pulp cells, and this event was inhibited by catalase. Exogenous addition of porcine esterase prevented BisGMA- and DBA-induced cytotoxicity. Interestingly, inhibition of CES by bis(p-nitrophenyl) phosphate (BNPP) and CES2 by loperamide enhanced the cytotoxicity of BisGMA and DBA. Addition of porcine esterase or N-acetyl-l-cysteine prevented BisGMA-induced prostaglandin E(2) (PGE(2)) and PGF(2α) production. In contrast, addition of BNPP and loperamide, but not mevastatin, enhanced BisGMA-induced PGE(2) and PGF(2α) production in dental pulp cells. These results suggest that BisGMA may induce the cytotoxicity and prostanoid production of pulp cells, leading to pulpal inflammation or necrosis via reactive oxygen species production. Expression of CES, especially CES2, in dental pulp cells can be an adaptive response to protect dental pulp against BisGMA-induced cytotoxicity and prostanoid release. Resin monomers are the main toxic components in DBA, and the ester group is crucial for monomer toxicity.

Prostaglandin F(2alpha) stimulates MEK-ERK signalling but decreases the expression of alkaline phosphatase in dental pulp cells.

AIM: To study prostaglandin F(2alpha) (PGF(2alpha)) receptor expression and downstream signalling in cultured human dental pulp cells and the effect of PGF(2alpha) on the alkaline phosphatase (ALP) activity of dental pulp cells. METHODOLOGY: Human dental pulp cells were cultured and exposed to PGF(2alpha). The expression of PGF(2alpha) (FP) receptors was analysed by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. The activation of extracellular regulated kinase (ERK) and cAMP responsive element binding protein/activating transcription factor-1 (CREB/ATF-1) signalling was determined by Western blotting. The expression of ALP in pulp cells after exposure to PGF(2alpha) was evaluated by ALP staining and PCR. RESULTS: Dental pulp cells expressed FP receptor mRNA and protein. Exposure to PGF(2alpha) revealed little cytotoxicity to pulp cells. PGF(2alpha) induced both ERK and CREB/ATF-1 phosphorylation in pulp cells. Exposure to PGF(2alpha) (>1 micromol L(-1)) further decreased the ALP activity and mRNA expression. However, U0126 (an inhibitor of MEK1) showed little preventive effect on the decline of ALP activity in dental pulp cells by PGF(2alpha). CONCLUSION: PGF(2alpha) may potentially activate FP receptors leading to ERK/CREB-ATF-1 activation during its production in inflamed dental pulp. PGF(2alpha) attenuated the ALP activity of pulp cells possibly via pathways not solely by MEK/ERK activation. PGF(2alpha) is a contributing factor of pulpal inflammation by regulating the activities of pulp cells.

Comparative cytotoxicity of five root canal sealers on cultured human periodontal ligament fibroblasts.

AIM: To evaluate the cytotoxicity of current root canal sealers to periodontal ligament (PDL) fibroblasts. METHODOLOGY: Five root canal sealers (Canals, Canals-N, Topseal, Sealapex, Tubliseal) were prepared and placed into transwells. After initial setting for 1 h, the transwells with sealers were placed into cultured PDL fibroblasts. They were cultured for further 3 or 18 h. Morphological changes were observed. Cell viability was estimated by 3-(4,5-dimethyl-thiazol-2-yl)-2,5- diphenyl-tetrazolium bromide (MTT) assay. RESULTS: Marked retraction and death of PDL fibroblasts were observed after exposure to Canals or Topseal for 3 h. A 3-h exposure of PDL fibroblasts to Tubliseal stimulated MTT reduction. Canals-N showed little cytotoxicity even after an exposure of 18 h. CONCLUSION: Canals was the most toxic sealer, followed by Topseal. Sealapex and Tubliseal had comparable and moderate cytotoxicity to PDL fibroblasts, whereas Canals-N showed little cytotoxicity. Exposure to Tubliseal may modulate MTT reduction in PDL fibroblasts. Canals-N had good biocompatibility.

Nitric oxide promotes the progression of periapical lesion via inducing macrophage and osteoblast apoptosis.

This study aimed to elucidate the modulation by nitric oxide (NO) of the apoptosis of macrophages and osteoblasts, the essential cellular components in the development of periapical lesions. Lipopolysaccharide (LPS) induced prominent nitrite synthesis in J774 mouse macrophage cell lines. Exposure to LPS induced obvious apoptosis in J774 cells, whereas transient transfection with murine inducible nitric oxide synthase (iNOS), small interfering RNA (siRNA) diminished this effect. Tumor necrosis factor-alpha (TNF-alpha) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) (a NO donor) triggered apoptosis in UMR-106 rat osteoblastic cell lines and a synergistic effect was noted when TNF-alpha and SNAP were added to the medium together. Administration of siRNAs for c-Fos and c-Jun: components of activator protein-1 (AP-1) and transforming growth factor-beta1 attenuated the combined effect markedly. Terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) stain in a rat model of induced periapical lesion showed positive apoptotic signals in macrophages and osteoblasts. Administration of N(G)-monomethyl-l-arginine markedly diminished the extent of bone loss and the amounts of apoptotic macrophages and osteoblasts. In conclusion, NO mediates LPS-stimulated apoptosis of macrophages. It also induces osteoblast apoptosis and augments the pro-apoptotic effect of cytokines. Inhibition of NO synthesis in vivo attenuates apoptosis and the size of periapical lesions. Taken together, these results suggest that NO may promote the progression of periapical lesion by inducing the apoptosis of macrophages and osteoblasts.

The effects of masseter muscle pain on biting performance.

The present study applied a standardized test food of known hardness to evaluate the biting performance of 20 female patients who had pain mainly in the masseter muscle during palpation. Another 20 women of a similar age group who were pain-free during examination served as controls. Electromyograms (EMG) of the masseter and sternocleidomastoid (SCM) muscles and the jaw position were recorded and measured when the subjects were biting through two types of test foods with known hardness (hard type, 20 kg hardness and extra-hard type, 60 kg hardness). Pressure-pain-threshold (PPT) values of both the patients and the normal subjects were obtained with an algometer. It was found that the PPT of the patients with pain was significantly lower and that the extra-hard food took more masseter muscle activity and more working side jaw movement in both the pain and the normal groups. During both hard and extra-hard food biting, a significantly longer duration of masseter muscle activity was found in pain patients while the total muscle activity was not significantly stronger. Strong correlation existed between SCM and masseter muscle activity during both hard and extra-hard food biting in the patient group, while such correlation was very weak in the normal group. In conclusion, painful masseter muscles required longer masseter and SCM muscle contraction time for breaking through a hard food of 20 kg and more, and co-activation of SCM and masseter muscles existed and was more evident when the food was harder or the pain was more severe.

Effects on non-human primate mastication of reversible inactivation by cooling of the face primary somatosensory cortex.

Rhythmical jaw movements can be evoked by intracortical microstimulation within four physiologically defined regions, one of which is the primary face somatosensory cortex (face SI). It has been proposed that these regions may be involved in the selection and/or control of masticatory patterns generated at the brainstem level. The aim here was to determine if mastication is affected by reversible, cooling-induced inactivation of the face SI. Two cranial chambers were chronically implanted in two monkeys (Macaca fascicularis) to allow access bilaterally to the face SI. A thermode was placed on the dura or pia overlying each SI that had been shown with micro-electrode recordings to receive intraoral inputs. A hot or cold alcohol-water solution was pumped through the thermodes while the monkey chewed a small piece of apple or a sultana during precool (thermode temperature, 37 degree C), cool (2-4 degrees C), and postcool (37 degrees C) conditions. Electromyographic (EMG) activity was recorded intramuscularly from the masseter, genioglossus, and anterior digastric. Cooling of SI impaired rhythmical jaw and tongue movements and EMG activity associated with mastication in one monkey (H5), and modified the pattern of EMG activity in the other (H6). The total masticatory time (i.e., time taken for chewing and manipulation of the bolus before swallowing) was increased. This was due principally to an increase in the oral transport time (i.e., time taken for manipulation of bolus after chewing and before swallowing: monkey H6, control, 2.7 sec; cool, 5.2 sec, p < 0.05); the bolus was manipulated by the tongue during this period before swallowing. Within the chewing time (i.e., time during which chewing occurred), cooling resulted in a significant increase in anterior digastric muscle duration, a significant delay in the onset of masseter EMG activity, and a significant increase in the variance of genioglossus EMG duration. The data support the view that the face SI plays a part in modulating the central pattern generator for mastication.

An electromyographic analysis of orofacial motor activities during trained tongue-protrusion and biting tasks in monkeys.

This study sought to characterise the electromyographic (EMG) activity patterns of orofacial-muscles during trained tongue-protrusion and biting tasks in two awake monkeys (Macaca fascicularis). Chronic or acute EMG electrodes were placed in the anterior digastric (DIG), genioglossus (GG), masseter (MASS), platysma (PLAT), zygomaticus major (ZYGO), orbicularis oris superior (OOS), and orbicularis oris inferior (OOI) muscles and their EMG activity as well as the force signals of the tongue-protrusion and biting tasks were recorded. A total of 327 tongue-protrusion task trials and a total of 210 biting-task trials were successfully completed in several recording sessions and the EMG patterns were generally consistent between the different sessions. For the tongue task, the mean onset time of increase in GG activity significantly (p < 0.0001) led the mean onset time of increase in the force. The DIG, GG, and OOI (and also the OOS in one of the monkeys) showed a significant (p < 0.0001) increase in mean EMG amplitude during the holding phase, but the GG in both monkeys had the highest mean EMG amplitude ratio (MAR), i.e. the mean EMG amplitude during the holding or dynamic phase divided by the mean EMG amplitude during the pre-trial period. A similar EMG pattern was documented for different directions of the tongue-protrusion task (right, symmetrical, and left) and changes in the levels of EMG activities occurred in GG and OOI as the direction of the tongue-protrusion task changed from left to right. The task at different forces was associated with no apparent change in MAR for the holding phase for each muscle recorded. However, during the dynamic phase, only the GG showed a significant increase in EMG activity as the forces were increased. For the biting task, the mean onset times of the MASS activity and force were not significantly different. The MASS and ZYGO muscles (and the PLAT in one of the monkeys) showed a significant increase in mean EMG amplitude during the holding phase compared with the pre-trial period, and the MASS showed the highest MAR. It was also the only muscle showing a significant increase in the EMG activity when the bite-force level was increased. These findings reveal that certain orofacial muscles are selectively recruited during the two different orofacial tasks.(ABSTRACT TRUNCATED AT 400 WORDS)

Functional properties of single neurons in the primate face primary somatosensory cortex. I. Relations with trained orofacial motor behaviors.

1. We have demonstrated recently that reversible, cooling-induced inactivation of the face primary somatosensory cortex (SI) severely impairs the successful performance of a tongue-protrusion task but has relatively minor effects on the performance of a biting task. In an attempt to establish a neuronal correlate for these different behavioral relations, the present study was initiated to document the mechanoreceptive field properties of a population of face SI neurons and their activity during the tongue-protrusion and biting tasks. 2. Within SI, the representation of the face was found immediately lateral to that of the hand, and there was a clear somatotopic pattern of organization within face SI: the periorbital or nose region was located most medially in the face SI, then followed laterally in sequence the representation of the upper lip, lower lip, and intraoral area. A mechanoreceptive field (RF) was identified for 253 neurons, which included 162 "lip RF" neurons receiving mechanosensitive afferent inputs from the upper lip, lower lip, or both; 72 "tongue RF" neurons that received mechanosensitive afferent inputs from the tongue; 11 "periodontium RF" neurons receiving periodontal inputs; and 8 neurons that received inputs from other orofacial regions. 3. Nearly all (249/253) of the face SI neurons responded to light tactile stimuli, and most of them received contralateral inputs (78%) and showed a rapidly adapting (RA) response to tactile stimulation (82%). There was no significant difference in the ratio of slowly adapting (SA) to RA neurons in areas 3b and 1. 4. For 193 neurons studied in one or both of the orofacial tasks, 113 were found, on the basis of histological reconstruction, to be distributed in area 1, 61 in area 3b, and 19 in area 2. 5. The firing rate of most tongue RF (79% of 56) neurons and lip RF (60% of 93) neurons tested was significantly altered during the tongue-protrusion task. Only some (14% of 36 tongue RF neurons and 34% of the 92 lip RF neurons tested) showed a significant change in firing rate during the biting task. Three of 7 periodontium RF neurons studied in the tongue-protrusion task altered their firing rate and 5 of 10 altered their firing rate during the biting task. 6. Most of the 116 face SI neurons studied during both tasks exhibited a preferential relation to the tongue-protrusion task as distinct from the biting task, and none showed task-related activity during the biting task only.(ABSTRACT TRUNCATED AT 400 WORDS)

Functional properties of single neurons in the primate face primary somatosensory cortex. II. Relations with different directions of trained tongue protrusion.

1. In previous papers we have presented evidence suggesting an important role for the face primary somatosensory cortex (SI) in the fine control of tongue movements. These findings, plus our earlier evidence that many neurons in face motor cortex (MI) may exhibit firing rates related to the direction of tongue protrusion, led us to test the hypothesis that variations in the direction of a tongue-protrusion movement would be associated with variations in the activity of different face SI neurons. 2. Two monkeys were trained to perform a tongue-protrusion task in each of three directions: the task transducer was positioned at 0 degrees, 30 degrees to the left, or 30 degrees to the right from the midsagittal plane. The latter two positions were termed asymmetrical tongue-protrusion task positions. Single-neuron activity was recorded from face SI during trials of the tongue-protrusion task at each of two or three of the above positions. In addition, the mechanoreceptive field (RF) was delineated for each neuron. 3. Directional relations were found in 25 (58%) of the 43 neurons studied; this included 20 neurons showing a significant direction-by-time interaction in firing rate, i.e., the change of firing rate from the pretrial period to the task period was significantly different between different directions, and 5 showing no direction-by-time interaction but a significant difference in firing rate between different directions of the tongue-protrusion task. 4. Of the 43 neurons investigated, 21 and 20 had a RF on the tongue and lips, respectively ("tongue RF" and "lip RF" neurons), and the remaining 2 received mechanosensitive afferent inputs from other orofacial regions. There was no significant difference in the incidence of directional sensitivity between the neurons with a tongue RF and those with a lip RF (12/21 and 11/20, respectively). 5. Eight of the 25 "directional" neurons were located in area 3b and 17 in area 1. There was no significant difference in the proportion of directional neurons between areas 3b and 1. 6. The increase in discharge frequency at the preferred direction was, on the average for the 25 directional neurons, 39% over the mean discharge frequency observed during the task period for all directions of the tongue-protrusion task. Eight directional neurons showed a significant increase in firing rate during the tongue-protrusion task up to 130 ms before the onset of genioglossus electromyographic activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Functional properties of single neurons in the primate face primary somatosensory cortex. III. Modulation of responses to peripheral stimuli during trained orofacial motor behaviors.

1. In previous papers we have demonstrated that most single neurons in the face primary somatosensory cortex (SI) alter their firing rate during a trained tongue-protrusion task and some also during a trained biting task. Although the data suggest that some of the task-related activity in face SI might conceivably come from reafferent inputs from moving orofacial structures, it is possible that orofacial inputs are modulated during the trained orofacial movements. This study was initiated to investigate the possible modulation of evoked orofacial somatosensory responses of face SI neurons during trained tongue-protrusion and biting tasks. 2. Two monkeys were trained to perform a tongue-protrusion and a biting task and to accept stimulation applied to the facial skin or the lingual nerve during the tasks. For SI neurons with a tongue mechanoreceptive field (RF), electrical stimulation was applied to the lingual nerve to elicit neuronal activity; for SI neurons with a RF at the other locations, electrical or mechanical stimulation was applied to the RF to elicit neuronal activity. Modulation of neuronal activity evoked by low-threshold stimulation of the RF was tested, during the tongue-protrusion and/or biting tasks, in 44 face SI neurons and an additional 3 forelimb SI neurons with a palm RF (palm RF neurons). The 44 face SI neurons included 13 with a tongue RF (tongue RF neurons), 29 with a lip RF (lip RF neurons), and 2 with a lateral face RF (face RF neurons). 3. For face SI neurons tested during both force dynamic and holding phases of the task period, the evoked activity (i.e., the number of evoked spikes in 50 ms after the onset of stimulation) was decreased in at least one of the two phases for the majority (90%) of 31 neurons studied during the tongue-protrusion task and 61% of 23 studied during the biting task. The proportion of neurons modulated during the tongue-protrusion task was significantly higher than that during the biting task. For the 18 face SI tested during both tasks, a decrease in evoked activity occurred in 10 lip RF neurons for both tasks and in the remaining 5 lip RF and 3 tongue RF neurons for the tongue-protrusion task only. No neurons tested showed a clear facilitation of evoked activity during the task period of either task.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of bilateral cold block of the primate face primary somatosensory cortex on the performance of trained tongue-protrusion task and biting tasks.

1. Studies using ablation, intracortical microstimulation (ICMS) and surface stimulation, and single-neuron recordings have suggested that the primate primary somatosensory cortex (SI) may play an important role in movement control. Our aim was to determine whether bilateral inactivation of face SI would indeed interfere with the control of tongue or jaw-closing movements. 2. Effects of reversible inactivation by cooling of face SI was investigated in two monkeys trained to perform both a tongue-protrusion task and a biting task. The cooling experiments were carried out after the orofacial representation within SI was identified by systematically defining the mechanoreceptive field of single neurons recorded in face SI. The deficits in the tongue or jaw-closing movement were evaluated by the success rates for the monkeys' performance of both tasks and by the force and electromyographic (EMG) activity recorded from the masseter, genioglossus, and digastric muscles associated with the tasks. 3. During bilateral cooling of face SI, there was a statistically significant reduction in the success rates for the performance of the tongue-protrusion task in comparison with control series of trials while the thermodes used to cool face SI were kept at 37 degrees C. Detailed analyses of force and EMG activity showed that the principal deficit was the inability of the monkeys to maintain a steady tongue-protrusive force in the force holding period during each trial and to exert a consistent tongue-protrusion force between different trials. The task performance returned to control protocol levels at 4 min after commencement of rewarming. 4. Identical cooling conditions did not significantly affect the success rates for the performance of the biting task. Although the extent of the deficit was not severe enough to cause a significant reduction in successful rates for the biting task, cooling did significantly affect the ability of the monkeys to maintain a steady force in the holding period during each trial and to exert a consistent force between different trials. In one monkey the success rate of the biting task was also not affected by bilaterally cooling of face SI with a pair of larger thermodes placed on the dura over most of the face SI, face primary motor cortex (face MI), and adjacent cortical regions.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of reversible inactivation by cooling of the primate face motor cortex on the performance of a trained tongue-protrusion task and a trained biting task.

1. Intracortical microstimulation (ICMS) and surface stimulation studies of primate face motor cortex have shown an extensive representation within face motor cortex devoted to movements of the tongue and face; only a very small representation for jaw-closing movements has ever been demonstrated. These data suggest that face motor cortex plays a critical role in the generation of tongue and facial movements but is less important in the generation of jaw-closing movements. Our aim was to determine whether disruption of primate face motor cortical function would indeed interfere with the generation of tongue movements but would not interfere with the generation of jaw-closing movements. 2. The face motor cortex was reversibly inactivated with the use of cooling in two monkeys that were trained to perform both a tongue-protrusion task and a biting task. Recording of single neuronal activity in the cortex beneath the thermode confirmed the reversible inactivation of the cortex. Each task involved a series of trials in which the monkey was required to produce a preset force level for a 0.5-s force holding period; the monkey received a fruit-juice reward if it successfully completed a task trial. Cooling of the ICMS-defined face motor cortex was achieved bilaterally or, in one experiment, unilaterally by circulating coolant through thermodes placed either on intact dura overlying face motor cortex in both monkeys or directly on the exposed pia in one of the monkeys;thermode temperature was lowered to 3-5 degrees C during cooling. Electromyographic (EMG) recordings were also made from masseter, genioglossus, and digastric muscles. 3. During bilateral cooling of the thermodes on the dura overlying the face motor cortex, there was a significant reduction in the success rates for the performance of the tongue-protrusion task in comparison with control series of trials (i.e., precool and postcool) in which the thermodes were kept at 37 degrees C. Quantitative analyses of force and EMG activity showed that the principal deficit was an inability of each monkey to exert sufficient force with its tongue for a sufficient length of time onto the tongue-protrusion task transducer; this deficit was paralleled by a reduction in the level of genioglossus and digastric EMG activity. At 4 min after commencement of rewarming, task performance had returned to control, precool levels.(ABSTRACT TRUNCATED AT 400 WORDS)