Downregulation of Adhesion Molecule CHL1 in B Cells but Not T Cells of Patients with Major Depression and in the Brain of Mice with Chronic Stress.

Depression is a common serious mental disorder with unclear pathogenesis. Currently, specific diagnostic biomarkers are yet to be characterized. The close homolog of L1 (CHL1) is a L1 family cell adhesion molecule involved in the regulation of neuronal survival and growth. Although genome-wide expression profiling of human lymphoblastoid cell lines (LCLs) reported neural cell adhesion molecule (NCAM) L1 as a tentative biomarker for selective serotonin reuptake inhibitor (SSRI) antidepressant response, the involvement of CHL1 in depression is unclear. In this study, using a well-established chronic unpredictable mild stress (CUMS) depression mouse model, we examined the mRNA and protein expression of CHL1 in normal control, CUMS, vehicle (VEH), fluoxetine (FLU), and clozapine (CLO) groups. We found that in the CUMS group, both mRNA and protein expression of CHL1 were downregulated in both the hippocampus and the cortex. Treatment of CUMS mice with FLU and CLO reversed CHL1 mRNA and protein expression. In the human study, we showed that CHL1 expression was significantly downregulated in monocytes of unipolar and bipolar depressive patients compared with healthy donors (HD) at both mRNA and protein levels. Consistently, ELISA showed that CHL1 levels in the serum of patients with depression were reduced and negatively correlated with their HRSD-21 scores. Further flow cytometry studies showed that the reduced number of CHL1 positive CD19+ and CD20+ B cells of patients with depression was subsequently reversed with antidepressant treatment. Our findings suggested that downregulation of CHL1 from both immune cells and the brain may be linked to the immunopathogenesis of depression. In conclusion, CHL1 may be an important predictive marker for both diagnosis and treatment outcome of depression.

Effect of amiloride and selected analogues on postischemic recovery of cardiac contractile function.

The purpose of the present study was to compare the protective effects of amiloride and three of its derivatives (which are selective inhibitors of Na(+)-H+ exchange) during postischemic reperfusion. Previously, amiloride has been shown to have a protective effect on ischemia-reperfusion injury. However, because of its nonselective actions, the mechanism of its effect is unclear. 5-(N,N-dimethyl)-amiloride (DMA) is also protective and appears to act via inhibition of the Na(+)-H+ exchanger. However, corroborative effects using other selective Na(+)-H+ exchange blockers are needed. Amiloride, DMA, ethylisopropyl amiloride (EIPA), and 5-(N,N-hexamethylene)-amiloride (HMA) were included for 10 min in the reperfusion period after 60 min of global ischemia in the rat right ventricular wall. Peak developed tension and the rates of tension generation and relaxation were significantly improved during reperfusion in the presence of 100 microM amiloride, 10 microM DMA, 2.5 microM HMA, or 1 microM EIPA compared with those of drug-untreated muscles. Contracture formation was significantly depressed in the presence of these drug concentrations as was release of creatine kinase from the ventricular wall into the coronary effluent. The efficacy of these drugs for protecting the right ventricular wall from postischemic contractile dysfunction correlates well with their potency as blockers of Na(+)-H+ exchange. The results provide further evidence in support of a role for Na(+)-H+ exchange. The results provide further evidence in support of a role for Na(+)-H+ exchange in determining ischemia-reperfusion injury in the heart.

[The relationships between orthodontics and temporomandibular joint dysfunction. A review of the literature and longitudinal study]. / Zusammenhänge zwischen Kieferorthopdie und Kiefergelenksdysfunktion. Literaturübersicht und longitudinale Untersuchung.

The fist part of this study concerns a literature review on temporomandibular dysfunction (TMD). There exists an equal amount of literature relating occlusal interferences to TMD, as there are reports denying any causal relationship. It is remarkable, however, that the latter reports are relatively recent. The relationship between the Angle classification and TMD is reported to be only weak in a "normal" orthodontic population. The relationship between morphologic malocclusion, e.g. deep bites or crossbites, with TMD seems to be somewhat stronger. The vast majority of the reports did not find any relationship between TMD and orthodontic treatment or extractions. Our own longitudinal prospective study could not reveal any systematic relationship between orthodontic treatment or extractions and TMD.

Influence of perfusate pH on the postischemic recovery of cardiac contractile function: involvement of sodium-hydrogen exchange.

During reperfusion with pH 7.2 media after 55 min of ischemia, the recovery of developed tension (DT) and the maximal resting tension (RT) of the isolated right ventricular wall of rats were 58.8 +/- 6.5 and 201 +/- 20%, respectively, of the preischemic values. DT and RT in the ventricular wall perfused with pH 7.9 media for 6 min during reperfusion were 40 +/- 5.9 and 285 +/- 13%, respectively, of the preischemic values (P less than .05 vs. pH 7.2 group). The Na(+)-H+ exchange inhibitor, 5-(N,N-dimethyl)amiloride (DMA), effectively antagonized the detrimental effect of pH 7.9 media. A pH 6.5 media inhibited DT recovery and the rise in RT in the first 6 min of reperfusion. Subsequent reperfusion with pH 7.2 media resulted in cardiac dysfunction similar to that observed when reperfused at pH 7.2 only. Cellular Na+ and Ca++ were significantly elevated after 6 min of reperfusion at pH 7.2. Na+ and Ca++ levels were increased further if reperfusion was carried out at pH 7.9. Inclusion of 20 microM DMA during reperfusion at 7.9 significantly reduced cellular Na+ and Ca++. Creatine phosphokinase activity in the coronary effluent rose significantly during reperfusion at pH 7.2 and this was exacerbated if the reperfusion pH was 7.9. DMA treatment during reperfusion could significantly inhibit this elevation. The data lend further support for an important role of Na(+)-H+ exchange in the development of ischemia-reperfusion injury.

Protective effects of 5-(N,N-dimethyl)amiloride on ischemia-reperfusion injury in hearts.

An Na(+)-H+ exchange inhibitor, 5-(N,N-dimethyl)amiloride (DMA), was used to probe the possible role of Na(+)-H+ exchange in ischemia-reperfusion injury in coronary perfused isolated rat right ventricular wall. In DMA-untreated hearts, 60 min of ischemia resulted in a significant rise in testing tension (RT: 174 +/- 8% of preischemic level). Thirty minutes of reperfusion further increased RT (273 +/- 12%) and induced a poor recovery in developed tension (DT: 28 +/- 4%). Both the rate of tension development and relaxation (+dT/dt and -dT/dt) recovered to a similar degree. When 1, 5, or 20 microM DMA was included in the perfusate (3 min before ischemia and in the first 3 min of reperfusion), the maximal postischemic RT of the heart was reduced to 204 +/- 21, 166 +/- 15, and 139 +/- 45% of the preischemic levels (P less than 0.05), respectively, and DT was 39 +/- 3, 63 +/- 10, and 79 +/- 8% of the preischemic levels (P less than 0.05), respectively. Similar qualitative recovery of +/- dT/dt was observed. Recovery was similar if DMA was present only during reperfusion. DMA treatment also significantly protected against creatine phosphokinase release during reperfusion. The results demonstrate that DMA can significantly protect the heart during the initial stages of reperfusion. The data suggest that Na(+)-H+ exchange may play an important role in the development of cardiac dysfunction and damage during the first minutes of reperfusion.

Effect of platelet-activating factor (PAF) on sodium calcium exchange in cardiac sarcolemmal vesicles.

The effects of platelet-activating factor (PAF) on Na(+)-dependent calcium uptake in myocardial sarcolemmal vesicles were examined in order to clarify its mechanism of inotropic action on the heart. PAF (40 and 20 microM) significantly inhibited Na(+)-Ca2+ exchange by 61% and 37%, respectively. Both initial rate of exchange and maximal exchange were inhibited. The Km for the reaction was not altered but Vmax was lowered 55% by PAF. Lyso-PAF inhibited Na(+)-Ca2+ exchange to a similar degree as PAF. CV-3988, a specific PAF receptor antagonist, failed to diminish the inhibitory effect of PAF on Na(+)-Ca2+ exchange, suggesting that the effect of PAF on Na(+)-Ca2+ exchange is not via a receptor mechanism. The passive permeability of sarcolemmal vesicles to Ca2+ was markedly elevated after PAF treatment. However, this effect could not account for the decrease in Na(+)-Ca2+ exchange. Interestingly, passive Ca2+ binding to cardiac sarcolemma was increased by 40 microM PAF. This study indicates that a depression of Na(+)-Ca2+ exchange probably does not play a role in the negative inotropic effect of PAF on the myocardium under physiological conditions. Its mechanism of action on Na(+)-Ca2+ exchange is discussed.

Effects of chronic swimming training on cardiac sarcolemmal function and composition.

Cardiac contractile function is dependent on the integrity and function of the sarcolemmal membrane. Swimming exercise training is known to increase cardiac contractile performance. The purpose of the present study was to examine whether a swimming exercise program would alter sarcolemmal enzyme activity, ion flux, and composition in rat hearts. After approximately 11 wk of exercise training, cardiac myosin and actomyosin Ca2+-adenosinetriphosphatase (ATPase) activity was significantly higher in exercised rat hearts than in sedentary control rat hearts. Glycogen content was increased in plantaris and gastrocnemius muscles from exercised animals as was succinic dehydrogenase activity in gastrocnemius muscle of exercised rats in comparison to sedentary rat preparations. Sarcolemmal vesicles were isolated from hearts of exercise-trained and control rats. Sarcolemmal Na+-K+-ATPase and K+-p-nitrophenylphosphatase activities, Na+-Ca2+ exchange, and passive Ca2+ binding did not differ between the two groups. ATP-dependent Ca2+ uptake and 5'-nucleotidase activity were elevated in the cardiac sarcolemmal vesicles isolated from exercised animals compared with sedentary control rats. Sarcolemmal phospholipid composition was not altered by the exercise training. Our results demonstrate that swimming training in rats does not affect most parameters of cardiac sarcolemmal function or composition. However, the elevated sarcolemmal Ca2+ pump activity in exercised rats may help to reduce intracellular Ca2+ and augment cardiac relaxation rates. The enhanced 5'-nucleotidase activity may stimulate adenosine production, which could affect myocardial blood flow. The present results further our knowledge on the subcellular response of the heart to swimming training in the rat.

Growth changes in the nasal profile from 7 to 18 years of age.

Lateral head cephalograms of 17 male and 23 female subjects, aged 7 to 18 years, were evaluated for age changes in morphology and position of the nose with reference to the pterygomaxillary vertical plane. The study was confined to persons with normal facial profiles, normal overjets, and Class I molar relationships. Four linear and two angular dimensions were measured. Statistical analysis included the calculation of medians, Q ranges, proportion of growth completed at each age expressed as a percentage of the size of the variable at 18 years, and a pairwise correlation matrix. The results indicated that (1) increments in nose height, depth, and inclination are essentially complete in girls by 16 years of age, while continuing to increase in males up to and beyond 18 years; (2) the ratio of upper to lower nose heights remains at approximately 3:1 from 7 to 18 years in both sexes; (3) the ratio of nose depth to sagittal depth of the underlying skeleton changed from 1:2 at 7 years in both sexes to 1:1.5 in male subjects and 1:1.6 in female subjects at 18 years; (4) although upper nose inclination was similar for the two sexes, lower nose inclination was slightly larger in female subjects, especially after the age of 10 years; (5) persons with greater increments in nose depth than in nose height, or in nose depth than in the sagittal depth of the underlying skeleton, develop larger upper nose inclinations. The impact of nasal growth changes on orthodontic diagnosis and treatment planning was emphasized.