Limited evidence of chondrocyte outgrowth from adult human articular cartilage.

OBJECTIVE: Cellular outgrowth from articular cartilage tissue has been described in a number of recent experimental studies. The aim of this study was to investigate the occurrence of cellular outgrowth from articular cartilage explants isolated from adult human donors. METHOD: Macroscopically intact articular cartilage specimens were isolated from adult human donors and cultured either in their native status, or in a cleansed status achieved by forced washing to minimize attaching cells. Additionally, the effect of chemotactic stimuli including cell lysate, High-Mobility-Group-Protein B1 (HMGB-1), Trefoil-factor 3 (TFF3), bone morphogenetic protein-2 (BMP-2), transforming growth factor-ß1 (TGF-ß1), or three-dimensional fibrin or collagen matrices were investigated. Co-cultures with synovial membrane served as a positive control for a source of migratory cells. The occurrence of cellular outgrowth was analyzed by histological examination after a culture period of 4 weeks. RESULTS: Spontaneous cellular outgrowth from cleansed cartilage specimens was not observed at a relevant level and could not significantly be induced by chemotactic stimuli or three-dimensional matrices either. A forming cartilage-adjoining cell layer was only apparent in the case of native cartilage explants with cellular remnants from surgical isolation or in co-culture experiments with synovial membrane. CONCLUSION: The relevance of cellular outgrowth from cartilage tissue is largely absent in the case of adult human articular cartilage samples. A cartilage-adjoining cell layer forming around the explants may instead originate from still attaching cells that remained from surgical isolation.

Insular stroke is associated with acute sympathetic hyperactivation and immunodepression.

BACKGROUND AND PURPOSE: Post-stroke immunodepression has been related to brain lesion size but not a specific lesion location. Here, we studied the influence of lesion location within middle cerebral artery (MCA) territory on parameters related to activation of sympathetic adrenomedullar pathway, immunodepression, and associated infection. METHODS: We analyzed clinical, brain imaging, and laboratory data of 384 patients (174 women; mean age 70.8 ± 12.9 years) consecutively admitted to the stroke unit no later than 24 h after onset of acute ischaemic stroke involving the MCA territory. RESULTS: Patients with lesion affecting >33% of MCA territory had increased serum metanephrine and normetanephrine levels, elevated neutrophil counts but decreased eosinophil, helper T lymphocyte, and cytotoxic T lymphocyte counts compared to patients with lesion in <33% of MCA territory. Patients with large infarctions had increased frequency of infections within 14 days after stroke, especially chest infections (P < 0.001). Considering only patients with non-lacunar infarction in <33% of MCA territory, those with insular lesion had significantly higher normetanephrine levels, higher neutrophil but lower eosinophil and helper T lymphocyte counts than those with non-insular lesion, despite similar lesion diameters. This coincided with an increased frequency of chest infections (P < 0.01) in patients with insular lesion. Whilst patients with right insular lesion showed decreased heart rate variability, lesion laterality had no impact on laboratory findings or infection frequency. CONCLUSION: These findings suggest a specific role of insular lesion in the pathogenesis of stroke-induced sympathetic hyperactivation and immunodepression. Neuroimaging studies applying lesion volume calculation techniques are warranted to confirm these findings.

[Possible value of positive PSA levels in malignant and nonmalignant breast diseases]. / Mögliche Bedeutung eines positiven PSA-Nachweises bei Patientinnen mit benignen und malignen Erkrankungen der Brust.

Measurement of serum levels of PSA is widely used as a screening tool for prostate cancer. PSA has been shown to be associated with malignancies of many other organs than prostate, including the female breast. Therefore, PSA is not prostate-specific. PSA serum levels in females increase with excess of androgens. Variable PSA expression was observed in membranes of adipocytes of fat tissue and in the endothelium of small vessels in female and male breast. There is increasing evidence that androgens play a significant role in the development and progression of breast cancer. 5alpha-reductase is an enzyme that is expressed in androgen-dependent tissues, including the female breast, catalyzing the reduction of testosterone to its more bioactive form, dihydrotestosterone, which then transactivates a number of genes. One of these genes encodes for PSA, a favorable prognostic factor in breast cancer. Interactions of PSA and sex hormones in physiological processes and in prostatic and mammary cancer have been reported. The possible influence of PSA on breast cancer growth and progression and even its physiological functions are still under controversial debate. There are some findings which might indicate similarities in the influence of steroid hormones on the development of prostate and breast malignancies, perhaps a unique hormone-dependent molecular pathway for both types of cancer.

Serum-to-urinary prostate-specific antigen ratio in patients with benign prostatic hyperplasia and prostate cancer.

BACKGROUND: Prostate-specific antigen (PSA) is the single most important tumor marker in early detection and monitoring of prostate cancer (CaP). However, routine analysis of serum PSA concentrations does not allow differentiation between CaP and prostatic diseases. The aim of the present study was to evaluate the usefulness of the serum-to-urinary PSA ratio in a clinical setting. MATERIALS AND METHODS: In a retrospective clinical study, we determined serum and urine PSA concentrations in 48 patients with benign prostatic hyperplasia (BPH) and 57 patients with histologically confirmed CaP. RESULTS: The serum-to-urinary PSA ratio is able to discriminate BPH from CaP. CONCLUSIONS: Determination of the serum-to-urinary PSA ratio enhances the specificity of PSA in screening for CaP and monitoring of patients with CaP under androgen deprivation therapy.

[Carcinoid tumor with cystic liver metastases]. / Karzinoid mit zystischen Lebermetastasen.

Generally metastases of carcinoid tumours are pseudocystic in nearly 10% of the patients. In our case the guiding diagnostic importance of sonography and computed tomography could be proved. Results have to be completed by histologic findings and hormonal analysis (serotonin, 5-hydroxyindol acetic acid). - Morphological signs especially of the new imaging techniques are often a supposition for the modern therapy, e.g. the application of serotonin antagonists, local perfusion of cytostatic substances and if possible transplantation of the liver.

Hypoxic modulation of systolic blood pressure and urinary sodium excretion in spontaneously hypertensive rats after carotid body denervation.

To explore the role of arterial chemoreceptors, the effect of hypobaric hypoxia on urinary sodium excretion and systolic blood pressure was investigated in conscious spontaneously hypertensive rats (SHR) with carotid body denervation (CBD) or after sham-operation (SO). Denervation of the carotid bodies was performed by section of the carotid sinus nerves. Exposure to hypobaric hypoxia equivalent to high altitude of 4000 m led to a more pronounced decrease in systolic blood pressure in CBD-rats than in SO-rats. The pattern of urinary sodium excretion observed on the first two days of hypoxia in both groups was not affected by the chemodenervation. It is being suggested that arterial chemoreceptors do not play a critical role in blood pressure and natriuretic responses to hypobaric hypoxia in conscious SHR.

[The status of prazosin in therapy of chronic heart failure]. / Der Stellenwert des Prazosins bei der Therapie der chronischen Herzinsuffizienz.

Cardiac dysfunction and neurohumoral dysregulation show that the administration of vasodilators is reasonable in a cardiac insufficiency which is therapy-refractory against glycosides and saluretics. The alpha 1-blocker prazosin is a potent substance. On the basis of haemodynamic investigations of 55 patients the acute effects are demonstrated. Depending upon the degree of the cardiac insufficiency and the sympathetic dysregulation--measured at the behaviour of the resistance--the acute effects are convincing in more than 60% of the patients. For the long-term course patients with unequivocal initial improvement are suitable. This group can undergo a satisfactory therapy for a longer time by means of a carefully increased dosage, by corrections of the application of saluretics and by short interruptions of therapy and by the change of the dilator, respectively, or by an additional administration of another vasodilator. In the total spectre of the vasodilators which are administered in cardiac insufficiency prazosin occupies one of the first places.

[Cell distribution and macrophage function in bronchoalveolar lavage of patients with sarcoidosis and lung tumors]. / Untersuchungen zur Zellverteilung und Makrophagenfunktion in der Bronchoalveolären Lavage (BAL) von Patienten mit Sarkoidose und Lungentumoren.

BAL was performed to differentiate cases of sarcoidosis and bronchial carcinoma. Significant differences in the cell differentiation are stated. An increase of spontaneous interleukin production seems to be another sign of activity of sarcoidosis.

Comparison of the response of renal sodium excretion to almitrine and hypoxia in conscious normotensive and spontaneously hypertensive rats.

The effect of hypobaric hypoxia and almitrine on renal sodium excretion and systolic blood pressure was investigated in conscious adult normotensive control rats (NCR) and spontaneously hypertensive rats (SHR). Moderate hypoxia caused a significant natriuresis within the first two days in both NCR and SHR. The systolic blood pressure was significantly diminished in SHR only. Oral application of almitrine (1.0 mg/kg b.w.) induced natriuresis in SHR and NCR. However, there are considerable differences in the pattern of natriuresis between the animals of both strains and when compared to the effect of hypoxia. The urinary sodium excretion by almitrine was not associated with a decrease in systolic blood pressure neither in SHR nor in NCR. The results indicate that both hypoxia and almitrine induce a strong natriuresis in conscious rats apparently by different mechanisms. However, there is no real evidence at present as to whether the peripheral arterial chemoreceptors are indeed involved in these mechanisms, or not, and if so, to what degree.

Kidney function during arterial chemoreceptor stimulation. III. Long-lasting inhibition of renal tubular sodium reabsorption due to pharmacologic stimulation of the peripheral arterial chemoreceptors with almitrine bismesylate.

The reactions of the mean systemic arterial blood pressure, arterial acid-base balance kidney function (clearance-technique), and plasma aldosterone concentration (radio-immunoassay) elicited by stimulation of the peripheral arterial chemoreceptors with almitrine bismesylate were determined in chloralosed, non-vagotomized, spontaneously breathing cats in moderate mannitol-saline diuresis. The left renal nerves were cut; urine was collected separately from both the innervated and denervated kidneys. Intravenous injection of 0.2 mg/kg of the drug caused the expected long-lasting increase of the pO2 and pH and a decrease of pCO2 in the arterial blood, whereas the mean systemic arterial blood pressure slightly rose by an average of 2-4 mm Hg in the first hour of chemoreceptor stimulation but afterwards considerably decreased below the pre-injection values. The renal responses were characterized by a moderate vasoconstriction particularly in the innervated kidneys and a pronounced increase of sodium and urine excretion especially in the denervated kidneys. The inhibition of renal tubular sodium reabsorption underlying these natriuretic and diuretic reactions was fully demonstrable even at the end of the experiments, i. e. 4 h after the administration of the agent. Plasma aldosterone increased with the time of the experiments but did not show any clear relationships to the activity of the arterial chemoreceptors. The results show that the intravenous injection of almitrine bismesylate is connected with a renal response pattern which is typical for an excitation of the peripheral arterial chemoreceptors, i. e. moderate vasoconstriction (efferently mediated by the renal nerves) and an inhibition of renal tubular sodium reabsorption (efferently mediated by hormonal mechanisms). Furthermore, the data suggest that, on the one hand, under certain conditions these reactions of the kidney function could play the role of undesirable side effects but, on the other hand, the inhibition of renal tubular sodium reabsorption caused by almitrine bismesylate might possibly be used to treat diseases that are connected with a reduced ability of the kidneys to sufficiently excrete sodium.

Kidney function during arterial chemoreceptor stimulation. II. Suppression of plasma aldosterone concentration due to hypoxic-hypercapnic perfusion of the carotid bodies in anaesthetized cats.

The reactions of the mean systemic arterial blood pressure, kidney function (clearance technique) and plasma aldosterone concentration (radio-immuno-assay) elicited by perfusion of the vascularly isolated carotid bodies with venous blood were studied in two series of chloralosed, vagotomized, relaxed, and constantly ventilated cats undergoing saline diuresis. In one group of animals the carotid body chemoreceptors were left intact; in the other one, they were abolished by injecting acetic acid into the glomera carotici. In the cats with intact chemoreceptors perfusion of the carotid bodies with venous blood immediately caused a small and transient increase of the blood pressure, whereas renal plasma flow tended to fall despite continuous chemoreceptor stimulation. Renal fractional sodium excretion already increased in the first 25 min of chemoreceptor stimulation, whereas plasma aldosterone concentration showed a significant decrease only after 45 min of venous perfusion of the glomera carotici. Plasma electrolytes changed only little at that time. No clear relationships between the responses of plasma aldosterone and those of the other parameters measured could be obtained. On subsequent perfusion of the carotid bodies with arterial blood plasma aldosterone returned to the values determined before chemoreceptor stimulation. Inactivation of the carotid body chemoreceptors per se already enhanced plasma aldosterone concentration. Perfusion of the glomera carotici with venous blood in the cats with abolished chemoreceptors did not suppress plasma aldosterone content. The data show that plasma aldosterone changes are not involved in the development of the initial phase (first hour) of the inhibition of renal tubular sodium reabsorption provoked by arterial chemoreceptor stimulation, but during long-lasting chemoreceptor stimulation they might contribute to the maintenance of this type of natriuresis. Furthermore the experiments suggest that the decrease of plasma aldosterone repeatedly observed during exposure of mammals to acute hypoxic hypoxia is possibly the reflex result of the stimulation of the arterial chemoreceptors.