Enzymologische Untersuchungen in der Synovialflüssigkeit bei Gonarthrosen

Zusammenfassung Bei 40 Patienten, die wegen einer Meniskopathie, begleitet von einer unterschiedlich stark ausgeprägten Arthrose am Kniegelenk, operiert wurden, konnten die Werte der Lactatdehydrogenase-Gesamtaktivität (LDH-T) und der LDH-H-Isoenzyme bestimmt werden. Die Ergebnisse zeigen, daß schwere Arthrosen ohne begleitende synovitische Reaktion und Fälle mit inaktiven, chronifizierten Synovitiden geringe, Befunde mit klinisch und makroskopisch-anatomisch aktiven Synovitiden (einschließlich sogenannter aktivierter Arthrosen) hohe LDH-Gesamtaktivitäten aufwiesen. Fernerhin fand sich durchwegs ein Überwiegen der LDH-H-Isoenzyme als Zeichen einer aeroben Stoffwechsellage.

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Enzyme studies of synovial fluid from osteoarthritis knee joints

Summary In 40 patients who were operated on for meniscopathy, accompanied by more or less severe arthroses of the knee joints, the total activity of LDH-T and of the LDH-H-isoenzyms could be evaluated. The data show that severe arthroses without any synovitic reactions as well as cases with inactive chronic synovitis showed small total activities of LDH, whereas cases with clinical and macroscopic-anatomically active synovitis (including the so-called activated arthroses) showed a great total activity of LDH. Furthermore the dominance of LDH-H-isoenzyms has been found to indicate an aerobic situation of the metabolism.

     

Effects of human cerebellar thalamus disruption on adaptive control of reaching

Lesion or degeneration of the cerebellum can profoundly impair adaptive control of reaching in humans. Computational models have proposed that internal models that help control movements form in the cerebellum and influence planned motor output through the cerebello-thalamo-cortical pathway. However, lesion studies of the cerebellar thalamus have not consistently found impairment in reaching or adaptation of reaching. To elucidate the role of the cerebellar thalamus in humans, we studied a group of essential tremor (ET) patients with deep brain stimulation (DBS) electrodes placed in the cerebellar thalamus. The stimulation can be turned on or off remotely and is thought to reduce tremor by blocking the spread of the pathological output from the cerebellum. We studied the effect of thalamic DBS on the ability to adapt arm movements to novel force fields. Although thalamic DBS resulted in a dramatic and significant reduction of tremor in ET, it also impaired motor adaptation: the larger the stimulation voltage, the greater the reduction in rates of adaptation. We next examined ET patients that had undergone unilateral thalamotomy in the cerebellar thalamus and found that adaptation with the contralateral arm was impaired compared with the ipsilateral arm. Therefore, although both lesion and electrical stimulation of the cerebellar thalamus are highly effective in reducing tremor, they significantly impair the ability of the brain to form internal models of action. Adaptive control of reaching appears to depend on the integrity of the cerebello-thalamo-cortical pathway.     

Platelet-rich plasma stimulates porcine articular chondrocyte proliferation and matrix biosynthesis

OBJECTIVE: Platelet-rich plasma (PRP) is a fraction of plasma that contains high levels of multiple growth factors. The purpose of this study was to examine the effects of PRP on cell proliferation and matrix synthesis by porcine chondrocytes cultured in alginate beads, conditions that promote the retention of the chondrocytic phenotype, in order to determine the plausibility of using this plasma-derived material for engineering cartilage. DESIGN: PRP and platelet-poor plasma (PPP) were prepared from adult porcine blood. Adult porcine chondrocytes were cultured in the presence of 10% PRP, 10% PPP or 10% fetal bovine serum (FBS) for 3 days. Cell proliferation, proteoglycan (PG) and collagen synthesis were quantified, and the structure of newly synthesized PG and collagen was characterized. RESULTS: Treatment with 10% PRP resulted in a small but significant increase in DNA content (+11%, vs FBS; P<0.01; vs PPP; P<0.001). PG and collagen syntheses by the PRP-treated chondrocytes were markedly higher than those by chondrocytes treated by FBS or PPP (PG; PRP: +115% vs FBS; +151% vs PPP, both P<0.0001, collagen; PRP: +163% vs FBS; +163% vs PPP, both P<0.0001). Biochemical analyses revealed that treatment with PRP growth factors did not markedly affect the types of PGs and collagens produced by porcine chondrocytes, suggesting that the cells remained phenotypically stable in the presence of PRP. CONCLUSION: PRP isolated from autologous blood may be useful as a source of anabolic growth factors for stimulating chondrocytes to engineer cartilage tissue.     

Evaluation of a sensitive colorimetric FXIII incorporation assay. Effects of FXIII Val34Leu, plasma fibrinogen concentration and congenital FXIII deficiency

There is an increasing interest in the role of coagulation factor XIII (FXIII) in cardio- and cerebrovascular diseases. It has recently been reported that a common G-->T point mutation in the A-subunit gene of FXIII, which codes for a valine (val) to leucine (leu) change (FXIIIVal34Leu), is protective against thrombotic diseases but seems to increase the risk of intracerebral bleeding. We developed a colorimetric incorporation assay for detection of FXIII activity based on incorporation of 5-(biotinamido) pentylamine (BAPA) into fibrin or fibrinogen. With this new assay, we studied the effects of FXIIIVal34Leu mutation, plasma fibrinogen concentration and congenital FXIII deficiency on FXIII activity. There are no data available about the ability of different FXIII assays to detect altered activity in FXIIIVal34Leu genotypes. We therefore compared our results determined by the incorporation method with a commonly used photometric method based on ammonia release after cross-linking of glycine-ethylester to a specific glutamine containing peptide substrate. We also determined FXIII A-subunit antigen (Ag) levels using enzyme-linked immunosorbent assay (ELISA) technique. The FXIIIVal34Leu genotype could not be detected either by the photometric method nor by the FXIII A-subunit ELISA. The incorporation assay showed an increased specific FXIII activity in subjects possessing the leu allele. The photometric assay and ELISA gave similar results independent from genotype. In patients with congenital FXIII deficiency before and after substitution, however, ELISA and the incorporation assay gave similar results, whereas the photometric assay showed consistently higher values. Our results show that the incorporation assay, not the photometric assay based on ammonia release, can be used for detection of elevated activity in subjects with FXIIIVal34Leu. Because of specificity and over a wide range sensitivity, the assay can also be used for determination of FXIII deficiency and monitoring of FXIII substitution therapy.     

Differential expression of functional guanylyl cyclases in melanocytes: absence of nitric-oxide-sensitive isoform in metastatic cells

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.     

Where are the children in family counseling? Results of an explorative study

Since the late seventies the family setting has become a normal model in counseling, not least because of the systemic change in psychotherapy. The lack of methodologically well-founded considerations on how to involve the children in the family talk is therefore even more surprising. In the present study 40 counselors were interviewed how they propose to fill the special gap in their practical work, what strategies they have developed to involve children and how important for them children are in the family talk. The result was that the majority of the counselors are adult oriented in their activities and rarely include the children actively in the interactive proceedings. Nevertheless all those interviewed regarded their presence as necessary because they provide helpful diagnostic assistance in uncovering and recognizing parental problems and relational conflicts.     

Naturalistic course of obsessive compulsive disorder and comorbid depression. Longitudinal results of a prospective follow-up study of 74 actively treated patients

Seventy-four patients who met DSM-III-R criteria for obsessive compulsive disorder (OCD) were studied in a prospective follow-up study in order to investigate course and prognosis of OCD with or without comorbid depressive symptomatology. Subjects were examined three times: at admission (baseline), 6 months later (follow-up 1) and 12 months after follow-up 1 (follow-up 2). At admission, 51 (72.9%) OCD patients were assessed as depressive by the Hamilton Depression Scale score. Between admission and follow-up 1, all patients received behavior therapy and a serotonin reuptake inhibitor, between follow-up 1 and follow-up 2 they received different kinds of treatment in order to maximize therapeutic effects. A 25% Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score reduction from admission to follow-up 2 and in addition, a total Y-BOCS score of below 16 at follow-up 2 was defined as 'good prognosis course'. The results obtained showed that OCD patients who followed a good prognosis course, showed no significant depressive symptomatology at follow-up 2 (p = 0.001). These results imply that patients with a diagnosis of OCD may present depression at admission and/or follow-up 1; however, if OC symptomatology decreases longitudinally, depressive symptoms disappear too. We may assume that OCD is dominant over depression, and it seems that a comorbid depression does not have any major influence on the prognosis of OCD.