Connective tissue metabolism in children with chronic renal failure

To assess the characteristics of connective tissue metabolism in chronic renal failure (CRF), urinary excretion of glycosaminoglycan (GAG) fractions and hydroxyproline (HYP) was determined in ten patients with CRF and in ten age-matched healthy children. CRF was found to be associated with elevated free HYP (19.9±6.1 vs 9.8±3.6 mol/day,P<0.05) and depressed peptide HYP excretion (33.1±13.5 vs 225.2±17.7 mol/day,P<0.01), a low rate of total GAG excretion (7.0±2.4 vs 16.1±1.9 mol uronic acid/day,P<0.05) with low chondroitin 4 — sulphate + chondroitin 6 — sulphate (Ch-Ss) (14.0±9.9 vs 65.0±22.1%) and a high proportion of non-sulphated or under-sulphated fractions, i.e. hyaluronic acid + chondroitin + heparan sulphate (HA+Ch+HS) (75.3±11.4 vs 31.5±5.7%). Urinary 3-methyl-histidine (3-met-HIS) excretion and plasma essential free amino acids did not differ in the two groups. In response to haemodialysis no consistent change occurred in urinary excretion of 3-met-HIS, peptide-bound HYP, total GAG or percentage distribution of individual GAG fractions. After haemodialysis all plasma amino acids decreased significantly, and there was a significant increase in urinary excretion of free HYP (P<0.05). We conclude that the alterations in urinary excretion of total and individual GAGs observed in CRF may reflect disturbed connective tissue metabolism which does not appear to be accounted for by protein malnutrition or enhanced protein breakdown and remains uninfluenced by haemodialysis therapy.     

Effect of vinpocetine on retrograde axoplasmic transport

Vinpocetine, a derivate of vincamine, is widely used in the clinical pharmacotherapy of cerebral circulatory diseases. Herewith we report on a novel effect of vinpocetine: inhibition of retrograde axoplasmic transport of nerve growth factor (NGF) in the peripheral nerve. Blockade of retrograde transport of NGF results in transganglionic degenerative atrophy (TDA) in the segmentally related ipsilateral superficial spinal dorsal horn, which is characterized by depletion of the marker enzymes fluoride-resistant acid phosphatase (FRAP) and thiamine monophosphatase (TMP). At the same time, pain-related neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), are depleted from lamina I-III from the segmentally related, ipsitateral Rolando substance of the spinal cord. On the basis of these experiments it is suggested that vinpocetine may result in a locally restricted decrease of nociception, that might be useful in clinical treatment of intractable pain. Pilot self-experiments support this assumption.     

Measurement of respiratory function in isolated cardiac mitochondria using Seahorse XFe24 Analyzer: applications for aging research

Mitochondria play a critical role in the cardiomyocyte physiology by generating majority of the ATP required for the contraction/relaxation through oxidative phosphorylation (OXPHOS). Aging is a major risk factor for cardiovascular diseases (CVD) and mitochondrial dysfunction has been proposed as potential cause of aging. Recent technological innovations in Seahorse XFe24 Analyzer enhanced the detection sensitivity of oxygen consumption rate and proton flux to advance our ability study mitochondrial function. Studies of the respiratory function tests in the isolated mitochondria have the advantages to detect specific defects in the mitochondrial protein function and evaluate the direct mitochondrial effects of therapeutic/pharmacological agents. Here, we provide the protocols for studying the respiratory function of isolated murine cardiac mitochondria by measuring oxygen consumption rate using Seahorse XFe24 Analyzer. In addition, we provide details about experimental design, measurement of various respiratory parameters along with interpretation and analysis of data.     

Evidence for a lipochaperonin: Association of active proteinfolding GroESL oligomers with lipids can stabilize membranes under heat shock conditions

During heat shock, structural changes in proteins and membranes may lead to cell death. While GroE and other chaperone proteins are involved in the prevention of stress-induced protein aggregation and in the recovery of protein structures, a mechanism for short-term membrane stabilization during stress remains to be established. We found that GroEL chaperonin can associate with model lipid membranes. Binding was apparently governed by the composition and the physical state of the host bilayer. Limited proteolysis of GroEL oligomers by proteinase K, which removes selectively the conserved glycine- and methionine-rich C terminus, leaving the chaperonin oligomer intact, prevented chaperonin association with lipid membranes. GroEL increased the lipid order in the liquid crystalline state, yet remained functional as a protein-folding chaperonin. This suggests that, during stress, chaperonins can assume the functions of assisting the folding of both soluble and membrane-associated proteins while concomitantly stabilizing lipid membranes.     

Die Bedeutung der Phagozyten und des T-Lymphozyten-Systems bei der Abwehr von Candida albicans-Infektionen*(Übersicht)

Zusammenfassung: Die Immunität gegenüber Candida-Infektionen stellt ein komplexes Geschehen dar. Als Ergebnis der unterschiedlichen Schädigungsmöglichkeiten der verschiedenen Abwehrfaktoren kommt es zur Variabilität der klinischen Erscheinungsformen der Candidosen. Zu ausgedehnten und schweren Mykosen kann es kommen bei Mängeln der Barrierefunkrion der Haut, bei verminderterbiologischerAktivitätderSchleinihäute, oder bei spontanenbzw. artefiziellen strukturellen oder funktionellen Schädigungen der Granulozyten und Lymphozyten. Summary: Immunity to Candida infections is based on a number of complex mechanisms. The diversity of clinical features of candidoses is determined by a variety of modes of impairment of the defense factors. Extended and severe mycoses may develop if the barrier function of the skin is damaged, if the mucous membranes lose their biological defense activity and if structural or functional deficiencies of polymorphonuclear cells or lymphocytes occur.     

Long Term Post-Treatment Follow-up of Onychomycoses Treated with Ketoconazole/Langzeit-Nachuntersuchungen mit Ketokonazol behandelten Onychomykosen

Summary: Between 1978–1982, 56 cases of mycoses of finger-nails and 47 mycoses of toe-nails caused by yeasts were treated with ketoconazole. During the follow-up period the patients were examined twice. The first control examination was carried out after 33.5 months on average, and the second after 61.7 months of the treatment During the observation period, the cure rate did not change in respect of finger-nail infections but decreased considerably in toe-nail mycoses.
Zusammenfassung: Zwischen 1978–1982 wurden Sproßpilz-Infektionen an 56 Fingernägeln und an 47 Fußnägeln mit Ketokonazol behandelt. Während einer Langzeit-Nachuntersuchung wurden die Patienten zweimal kontrolliert. Die erste Kontrolluntersuchung wurde durchschnittlich 33,5 Monate nach dem Abschluß der Behandlung, die zweite durchschnittlich nach 61,7 Monaten durchgeführt. Im Verlauf der Studie änderte sich die Heilungsquote der Fingernägel-Infektionen nicht, aber bei den Mykosen der Fußnägel ergab sich eine wesentliche Verringerung der Heilungsquote.     

Rapid re-enlargement of a macroprolactinoma after initial shrinkage in a young woman treated with bromocriptine.

We report the case of a macroprolactinoma in a 32-year-old woman, who presented with secondary amenorrhea, galactorrhea, increased plasma prolactin level (3259 ng/ml), headache and bi-temporal visual field defect. Magnetic resonance imaging showed a large pituitary tumor. The patient responded well to bromocriptine (7.5 mg/day) with improvement of clinical symptoms and normalization of plasma prolactin within a few weeks. After 4 months of treatment, tumor size was also reduced markedly. During continued treatment at the same dose of bromocriptine the plasma prolactin level remained normal, but after 8 months of treatment the patient suddenly complained of worsening of her visual fields, and magnetic resonance imaging indicated re-enlargement of the tumor. Bromocriptine was discontinued and transsphenoidal pituitary surgery was performed. After surgery the visual field defect improved, but postoperative plasma prolactin level (1104 ng/ml) and magnetic resonance imaging indicated a residual tumor. Postoperative treatment with quinagolide (0.15 mg/day) resulted in disappearance of all clinical symptoms, normalization of prolactin level and a reduction in size of the residual tumor. This case demonstrates that a dissociation of the inhibitory effect of bromocriptine on tumor size and prolactin level may rarely develop during the course of drug treatment in a patient with macroprolactinoma.