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Biomedical subjects

M Knorr

Publications and source records attributed to M Knorr.

At least 73 records · Page 4Linked to original sources

[Effect of anti-glaucoma eyedrops on cell differentiation of the conjunctiva].

After local application of pilocarpine (minimum 1%), timolol (0.5%) or levobunolol (0.5%) to 6 patients, cell differentiation of the conjunctival epithelium was compared to that in 48 healthy persons. The least difference was found after pilocarpine application. The five ultrastructurally defined cell types were found to vary least when compared to the same cell types in normal subjects. The patients treated with timolol and levobunolol showed a reduction in secretory epithelial cells, especially within the conjunctiva bulbi, and a pronounced increase in cells with rough endoplasmatic reticulum. In addition to a loss of desmosomes and zonulae occludentes on the cell surface, a minimum 1-year application of the three antiglaucomatous medications leads to a reduction in the microvilli and microplicae and, particularly in patients treated with beta blockers, to intracellular changes, specifically increased vacuolization and dilation of the rough endoplasmatic reticulum. The latter may be attributable to the action of benzalkonium chloride (present as a preservative in all three eye drops studied) on the superficial epithelial cells. The cytotoxic action of the preservative may be intensified by the simultaneous application of beta blockers due to their destabilizing effect on the tear film.

Cell Differentiation↗

[Activation of phosphatidylinositol metabolism of corneal epithelial cells by platelet derived growth factor].

Numerous recent studies have found that the ubiquitous platelet-derived growth factor (PDGF) is central to the regulation of proliferative processes. PDGF's mitogenic effect in many cell types, for instance, is made possible by a receptor-mediated activation of phospholipase C, the key enzyme in the phosphatidylinositol (PI) turnover in membranes. Activation of the PI turnover then leads to an increase in the intracellular concentration of inositoltriphosphate (IP3), which functions as a second messenger and mobilizes cytosolic-free calcium from the endoplasmatic reticulum. The goal of the present study was to show that PDGF in corneal epithelial cells stimulates this transmembrane signal transmission system. Cell incubation was carried out on long-term cultures of rabbit corneal epithelial cells. IP3 was determined by ion-exchange chromatography, as described by Berridge et al. PDGF in nanomolar concentrations (5-50 ng/ml) was found to induce a dose-dependent rise in IP3, which peaked after 60 s. The maximum 300% increase in IP3 was accompanied by a pronounced rise in cytosolic-free calcium. These results show that PDGF can activate PI turnover in corneal epithelial cells.

Animals↗

[The second, mucus-secreting system of the conjunctiva. Ultrastructural findings].

The second mucus-secreting system (type II cells according to our classification) of the conjunctiva is important for moisturization of the ocular surface epithelia. Ultrastructurally, a merocrine and an apocrine type of secretion can be differentiated. The merocrine secretion (epithelial cells containing homogeneous or inhomogeneous osmiophilic granules) appears more or less in all conjunctival areas. The apocrine mode of secretion is only found in the multilayered cylinder epithelium of the fornix conjunctivae. On the whole, the type II cells with inhomogeneous, osmiophilic vesicles are the most common. In the apical area of these cells secretory vesicles either coalesce with the cell membrane or they are completely released to the cell surface. Within the human conjunctiva about 10% of the superficial epithelial cells have secretory functions. Their number slightly increases in the temporal areas of the conjunctiva and in persons under 20 years and over 60 years of age. These results were obtained by electron microscopical investigations of conjunctival biopsies from 48 persons without conjunctival diseases.

Adolescent↗

Rapid activation of human platelets by low concentrations of low-density lipoprotein via phosphatidylinositol cycle.

The interaction of low-density lipoprotein (LDL) with the human platelet was investigated with regard to saturable high-affinity binding, shape change, cytosolic free Ca2+ concentration, phosphatidylinositol (PtdIns) turnover, and thromboxane B2 biosynthesis. The experiments show that LDL, at a concentration approximately 100 times lower than in plasma, causes platelet activation concomitantly with stimulation of the PtdIns cycle and thromboxane B2 formation, similarly to other activators of platelets. The effects of LDL were inhibited by high-density lipoprotein. The results suggest that activation of platelets by low concentrations of LDL may play a role in pathophysiological conditions and that platelet can serve as a model for studying the influence of LDL on various target cells.

Binding Sites↗

Low density lipoprotein causes general cellular activation with increased phosphatidylinositol turnover and lipoprotein catabolism.

Low density lipoprotein (LDL), at concentrations high enough for receptor binding but not high enough to saturate the receptor, induces activation of phosphatidylinositol (PtdIns) turnover in a variety of cell types with various biological functions. Using both biochemical and electron microscopic studies, we have shown that blood platelets take up and degrade LDL in a manner reminiscent of phagocytic cell types. The activation of both PtdIns turnover and LDL metabolism is inhibited by high density lipoprotein. Thus, LDL at hormonal concentrations causes general cellular activation. Since all cell types studied responded to LDL with increased PtdIns turnover and uptake of LDL cholesterol, the PtdIns cycle may also be involved in the cellular regulation of LDL cholesterol metabolism.

Animals↗

[Diagnostic value of atrial natriuretic peptide in hypertension and heart insufficiency].

Serum ANP levels were measured by radioreceptor assay in 40 patients with various forms of secondary hypertension and 6 patients with heart failure. In addition, serum ANP was determined in 4 patients with renal artery stenosis before and after dilatation, as well as in 5 anephric patients before and after haemodialysis. Our results showed elevated serum ANP level in most patients with various forms of secondary hypertension and chronic heart failure. A distinction between these two groups and a control group of healthy individuals was not possible due to the wide range and occasional normal levels in the first two groups. ANP levels in patients with renal stenosis decreased after dilatation but there was no correlation with the success of this procedure. A positive correlation between ANP and plasma renin level was detectable in patients with renal artery stenosis, but was also elevated in anephric patients with absent renin production. In summary, our results show that measurements of serum-ANP are of little significance in the diagnosis of hypertension and chronic cardiac failure.

Atrial Natriuretic Factor↗

ACE inhibitor versus beta-blocker in the treatment of essential hypertension.

It is to be expected that in the near future the success or failure of antihypertensive substances will be mainly determined by their spectrum of side effects so long as their antihypertensive efficacy is comparable. This double-blind study with crossover of enalapril and atenolol in 58 mild to moderate hypertensive patients is, as far as we know, the first clinical trial evaluating next to the antihypertensive efficacy also compliance and side effects. On the grounds of excellent compliance results (ca. 95%) blood pressure values as well as the incidence of side effects can be assumed to be accurate. Our results show that the antihypertensive efficacy of enalapril is comparable to that of atenolol. The number of patients with side effects did not differ significantly between enalapril and atenolol.

Adult↗

Prescription patterns and costs of antihypertensive drugs in two outpatient clinics: Zürich (Switzerland) and Münster (FRG), 1975-1985.

In the present study the prescription patterns and cost of antihypertensive drugs in two outpatient clinics located in two different countries (Zürich, Switzerland, and Münster, FRG), were analyzed from 1975 till 1985 by using representative random samples of hypertensive outpatients. Throughout the observed period the leading positions were held by diuretics and beta-blockers, whereas central sympatholytics and ganglion blockers nearly disappeared. A rapid increase in the use of calcium antagonists occurred within the last 2 analyzed years. Drugs in fixed combination containing reserpin showed a constant decrease during the observed period, whereas beta-blocker-containing combination drugs increased in both clinics. The comparison between the two clinics revealed only minor differences in the prescription pattern of the various known classes of antihypertensive drugs. However, marked differences were observed within given classes between the preferred products. Both in Zürich and Münster the mean annual drug cost per patient doubled from 1975 to 1985. Especially during the last few years these changes took place with a remarkable rapidity, obviously the result of a more intense promotion of new antihypertensive drugs.

Adrenergic beta-Antagonists↗

Effect of atrial natriuretic polypeptide on angiotensin II-induced increase of cytosolic free calcium in cultured smooth muscle cells.

We investigated the effects of angiotensin II (ANG II) and synthetic atrial natriuretic polypeptide (ANP) on cytosolic free calcium concentration [( Ca2+]i) of cultured rat vascular smooth muscle cells. Incubation with ANP alone showed little or no change in [Ca2+]i, whereas ANG II alone increased [Ca2+]i in a dose-dependent manner up to 164%, compared with basal levels of 253 +/- 17 nmol/l (mean +/- s.e.m.). Simultaneous addition of 10 nmol/l ANG II and varying concentrations of ANP produced a reduction in the ANG II-induced increase in [Ca2+]i. These data suggest that the vasorelaxant effect of ANP is at least partly mediated by changes in [Ca2+]i.

Angiotensin II↗

Enalapril as a first-step agent in essential hypertension: a comparative study with atenolol.

The aim of the present double-blind crossover study was to compare the antihypertensive efficacy and tolerability of enalapril and atenolol in 48 patients with mild to moderate essential hypertension. After a 2-week wash-out period, treatment was started with either enalapril 20 mg or atenolol 50 mg daily. In patients with a diastolic blood pressure value of more than 90 mmHg after 2 weeks of therapy, doses were doubled. After 4 weeks of therapy, cases were classified as responders (diastolic blood pressure less than or equal to 95 mmHg) or non-responders (diastolic blood pressure greater than 95 mmHg) and after a 2-week wash-out phase switched over to the alternative drug for another 4-week therapy period. Both substances significantly lowered mean systolic and diastolic blood pressure to a comparable degree. After 2 weeks, 57% of patients under enalapril and 59% under atenolol shared a satisfactory response, which did not change at the higher dose levels. After 4 weeks of therapy the incidence of side effects was slightly, but insignificantly, higher on atenolol than on enalapril. Thus, our results show that both agents seem equally qualified as first-step drugs in the treatment of mild to moderate essential hypertension.

Adult↗