Placental ultrasonographic biochemical and histochemical studies in human fetuses affected with Niemann-Pick disease type A

Placental ultrasonographic, bio- and histochemical studies were performed on four unrelated fetuses affected with Niemann-Pick disease Type A, following prostaglandin-induced abortion at about the 19th week of gestation. An accumulation of sphingomyelin in the placentae of affected fetuses indicates the essential role of the enzyme sphingomyelinase, even during the early stages of gestation. A fair correlation between histochemical localization of sphingomyelin in the placentae and ultrasonographic findings was found, indicating the value of ultrasonic echo wave information in the diagnosis of metabolic disorders.     

Stability of enzymes in urine at 37°C

The activity of alanine aminopeptidase, alkaline phosphatase, γ-gluta-myltransferase, lactate dehydrogenase and β-$\text{N-}\text{acetyl}\text{-}\text{d}\text{-}\text{glucosaminidase}$ in urine at 37°C was investigated by a model simulating in vivo conditions.The stability of these urinary enzymes is influenced particularly by pH. At low pH values in urine (about pH 5.0) the four first-mentioned enzymes rapidly lose a considerable part of their activity, whereas β-$\text{N-}\text{acetyl}\text{-}\text{d}\text{-}\text{glucosaminidase}$ is inactivated at higher pH values in urine (about at pH 8.0).This inactivation effect is also time-dependent and can be modified by urinary substances such as creatinine, urea and electrolytes. To avoid misinterpretation of enzyme activity determinations in urine, the simultaneous measurement of urinary pH should be performed.     

Induction of inflammatory cell accumulation by TM-N49 and promutoxin, two novel phospholipase A2

Local inflammation is a prominent characteristic of snakebite wound. Snake venom phospholipase A₂s (PLA₂s) are one of the main components which contribute to accumulation of inflammatory cells. We have isolated TM-N49 and promutoxin from Protobothrops mucrosquamatus venom and investigated their ability in induction of cell accumulation by using an in vivo mouse model. The results showed that both TM-N49 and promutoxin are potent stimuli for induction of neutrophil, lymphocyte, macrophage and eosinophil accumulation in the mouse peritoneum. The TM-N49- and promutoxin-induced inflammatory cell accumulation was inhibited by pretreatment of animals with cyproheptadine, terfenadine and Ginkgolide B, indicating that histamine and PAF is likely to contribute to the cells accumulation. Pre-injection of antibodies against adhesion molecules ICAM-1, CD18, CD11a and L-selectin showed that ICAM-1 is a key adhesion molecule of TM-N49- and promutoxin-induced lymphocyte, macrophage and eosinophil accumulation; CD18 and CD11a plays an important role in the migration of neutrophils, eosinophils and macrophages; and L-selectin is involved in the neutrophil and eosinophil accumulation. In conclusion, induction of inflammatory cell accumulation by TM-N49 and promutoxin confirms that group II PLA₂s is pivotal stimulus for cell infiltration, through which they participate in the formation of snakebite inflammation.     

??-Amphetamine and Antipsychotic Drug Effects on Latent Inhibition in Mice Lacking Dopamine D2 Receptors

Drugs that induce psychosis, such as 𝒟-amphetamine (AMP), and those that alleviate it, such as antipsychotics, are suggested to exert behavioral effects via dopamine receptor D₂ (D₂). All antipsychotic drugs are D₂ antagonists, but D₂ antagonism underlies the severe and debilitating side effects of these drugs; it is therefore important to know whether D₂ is necessary for their behavioral effects. Using D₂-null mice (Drd₂−/−), we first investigated whether D₂ is required for AMP disruption of latent inhibition (LI). LI is a process of learning to ignore irrelevant stimuli. Disruption of LI by AMP models impaired attention and abnormal salience allocation consequent to dysregulated dopamine relevant to schizophrenia. AMP disruption of LI was seen in both wild-type (WT) and Drd₂−/−. This was in contrast to AMP-induced locomotor hyperactivity, which was reduced in Drd₂−/−. AMP disruption of LI was attenuated in mice lacking dopamine receptor D₁ (Drd₁−/−), suggesting that D₁ may play a role in AMP disruption of LI. Further supporting this possibility, we found that D₁ antagonist {"type":"entrez-protein","attrs":{"text":"SKF83566","term_id":"1157390490","term_text":"SKF83566"}}SKF83566 attenuated AMP disruption of LI in WT. Remarkably, both haloperidol and clozapine attenuated AMP disruption of LI in Drd₂−/−. This demonstrates that antipsychotic drugs can attenuate AMP disruption of learning to ignore irrelevant stimuli in the absence of D₂ receptors. Data suggest that D₂ is not essential either for AMP to disrupt or for antipsychotic drugs to reverse AMP disruption of learning to ignore irrelevant stimuli and further that D₁ merits investigation in the mediation of AMP disruption of these processes.     

FN14 Signaling Plays a Pathogenic Role in a Mouse Model of Experimental Autoimmune Myocarditis

BackgroundThe pathogenesis of inflammatory cardiomyopathy is affected by the activation of autoimmune-mediated cascades. To study these cascades, we developed an experimental model of troponin I (TnI)-induced autoimmune myocarditis (EAM). One factor playing a pivotal role in the context of autoimmune disorders is the receptor fibroblast growth factor-inducible 14 (FN14). Thus, the impact of FN14 in the development of autoimmune myocarditis was investigated.Methods and ResultsTnI-immunization led to a significantly increased myocardial FN14 mRNA and protein expression in wild-type (wt) mice. To investigate the precise role of FN14 in EAM, FN14 knockout (ko) and wt littermates were immunized with TnI or control buffer. The animals were evaluated for cardiac parameters and indicators of myocardial injury. FN14 deficiency resulted in better cardiac performance, less myocardial inflammation, fibrosis, and cardiac damage. A lower myocardial mRNA expression of inflammatory cytokines and chemokines as well as their receptors could be demonstrated in TnI-immunized FN14ko compared to wt mice also immunized with TnI. Western blot analysis revealed a contribution of nuclear factor kappa-light-chain-enhancer of activated B cells to FN14-induced signaling cascades.ConclusionsIn the pathogenesis of autoimmune myocarditis, the inflammatory response to cardiac injury is attenuated in FN14ko mice. Thus, inhibition of FN14 in patients might represent a novel therapeutic strategy in the treatment of inflammatory cardiomyopathy.