Effects of inorganic divalent cations on the renal basolateral transport system for organic anions.

Recent work demonstrated that the heavy metal ion Cd2+ increases the transport of p-aminohippuric acid (PAH) across the basolateral membrane of microdissected non-perfused rabbit kidney S2 proximal tubule segments. Usually, such ions induce damage of various renal transport systems, therefore the effects of divalent metal ions Zn2+, Co2+ and Ni2+ on this transporter were investigated. Addition of Ni2+ or Zn2+ to the bathing solution leads to a significant reduction of basolateral PAH transport, with IC50 values of 2 x 10(-5) and 10(-6) M, respectively, whereas Co2+ failed to inhibit PAH accumulation. Simultaneous incubation with thrombin (10(-9)M), which is known to increase [Ca2+]i, abolished the effects of the divalent ions. Our results indicate that Ni2+ and Zn2+ reduce cellular PAH uptake. Because Ni2+ and Zn2+ are calcium channel blockers, these effects are probably due to a reduction of [Ca2+]i by an interaction of these metals with binding sites in the calcium channel, whereas Co2+ does not affect these binding sites. This finding is supported by the fact that thrombin abolished the cation effects.     

Preoperative radiotherapy for muscle-invading bladder-carcinoma

One hundred five patients with clinical stage T2-T4 transitional cell bladder carcinoma who completed either low-dose (20-26 Gy) or high dose (40-50 Gy) preoperative radiotherapy (RT) followed by cystectomy were reviewed. Five-year actuarial survival was 42%, 52%, and 17% for stages T2, T3, and T4, respectively. Five-year local control rates for stages T2, T3, and T4 was 93%, 93% and 22%, respectively. Survival, local control, distant metastasis and complications were similar for both preoperative regimens. The high rates of local control support the use of preoperative RT in selected patients with bladder carcinoma.     

Action of the competitive angiotensin II antagonist saralasin during the initial phase of glycerol-induced acute renal failure of the rat

Summary The effects of the competitive angiotensin II antagonist saralasin (1-sarcosine-8-alanine-5-isoleucine-angiotensin II) on renal function in healthy rats and in rats with myohemoglobinuric acute renal failure were studied. Acute renal failure was induced by an intramuscular injection of 50% glycerol (10 ml ·kg^–1). Functional impairment of the glycerol treated animals consisted in a decrease of renal blood flow (electromagnetic flowmeter) and GFR and in an increase of urine volume and arterial blood pressure.In healthy rats saralasin (6 g·kg^–1·min^–1 i.v.) had no renal effects by itself but antagonized the angiotensin II (200 ng·kg^–1·min i.v.) induced fall of renal blood flow and GFR and the increase of arterial blood pressure. Given to glycerol treated animals saralasin did not induce any change of arterial blood pressure, renal blood flow, GFR or the urinary excretion of fluid and sodium.Supported by Deutsche Forschungsgemeinschaft     

Transport of anionic drugs across the basolateral membrane of proximal S2 segments of the rabbit kidney. Inverse relationship between the affinity to the p-aminohippurate transport system and the transport rate

The renal p-aminohippurate (PAH) transport system, which resides in the S2 segments of proximal tubules, is a main tubular secretory system for drugs. Previous studies have shown that the hydrophobicity of drugs is positively correlated with their affinity for the basolateral PAH transporter. Affinity was deduced from inhibition of tubular 3H-PAH uptake. However, up to now, no studies are available which tested the relationship between hydrophobicity and transport rate of drugs. Therefore, in the present study, the basolateral transport rates of several drugs (probenecid, CAS 57-66-9, furosemide, CAS 54-31-9, bumetanide, CAS 28395-03-1, mefruside, CAS 7195-27-9) which are substrates of the PAH transporter and which differ markedly regarding their hydrophobic properties (log P values ranging from 1-3) were determined on non-perfused proximal S2 segments microdissected from rabbit kidneys without the use of enzymatic solutions. To measure the transport rate advantage of the finding was taken that the PAH transporter in the basolateral membrane of proximal S2 segments acts as a countertransporter which exchanges PAH with dicarboxylates (glutarate or alpha-keto-glutarate). Hence, the stimulatory effect of a drug on the 14C-glutarate efflux rate of 14C-glutarate preloaded S2 segments is a measure of its translocation across the basolateral cell membrane. The results revealed that with increasing hydrophobicity (mefruside < furosemide < bumetanide < probenecid) the stimulating effect of the drugs on 14C-glutarate efflux decreased indicating that the compounds are more slowly translocated although their potency to inhibit 3H-PAH uptake increased. Thus, an inverse relationship between hydrophobicity and hence affinity of the drugs for the PAH transporter and transport rate could be established.     

Pseudophakic retinal detachments. Anatomic and visual results.

Retinal reattachment rates and visual results were analyzed in 227 consecutive primary pseudophakic rhegmatogenous retinal detachments. The overall anatomic reattachment rate was 90%, with no significant difference between the anterior chamber (AC) and posterior chamber intraocular lens groups. Visual results were significantly worse in the AC lens group (P less than 0.05). Negative prognostic indicators for reattachment included age greater than 65 years, poorer preoperative vision, larger extent of the retinal detachment, inability to identify a retinal break, longer duration of symptoms before presentation, and grades C or D proliferative vitreoretinopathy (P less than 0.05). In addition to the above factors, eyes with AC reaction, AC lenses, and macular detachment had a poorer visual prognosis.     

Hydrostatische Drucke in proximalen und distalen Konvoluten und in peritubulären Capillaren von Rattennieren nach Furosemid und Acetazolamid

Zusammenfassung An Rattennieren wurden hydrostatische Drucke in proximalen und distalen Tubuli und in peritubulären Capillaren unter Kontrollbedingungen und nach Gabe von Acetazolamid und Furosemid gemessen. Die Kontrollwerte betrugen 11,5 mm Hg proximal und 4,9 mm Hg distal. Die Drucke stiegen nach Acetazolamid proximal auf 13,4 mm Hg und distal auf 10,8 mm Hg. Der Unterschied zwischen proximalen und distalen Drucken war auch nach Acetazolamid signifikant. Nach Furosemid nahm der proximale Druck im Mittel auf 32,7 mm Hg zu, der distale auf 29,5, die Differenz zwischen beiden war nicht mehr signifikant.Es bestand eine signifikante lineare Korrelation zwischen Drucken in proximalen und distalen Tubuli und Harnvolumen sowohl nach Acetazolamid als auch nach Furosemid. Der Druckanstieg bei zunehmendem Harnvolumen ist nach Entfernen der Nierenkapsel relativ geringer. Er ist im Vergleich zum Harnvolumen in den ersten 10 min nach Gabe von Furosemid größer als in der Folgezeit, obwohl das Harnvolumen später stärker zunimmt. Die Drucke in den peritubulären Capillaren lagen unter Kontrollbedingungen um 3,1 mm über den Drucken in proximalen Konvoluten, nach Furosemid dagegen um etwa denselben Betrag darunter.Es wird angenommen, daß der Strömungswiderstand der Henleschen Schleife mit zunehmendem Harnfluß stärker vermindert wird, während ein Widerstand am Ende des Nephrons zum Aufstau der intratubulären Flüssigkeit und zur Druckerhöhung führt, die die Erweiterung der Tubulusquerschnitte erzwingt.Auszugsweise vorgetragen auf der 32. Tagung der Deutschen Pharmakologischen Gesellschaft in Düsseldorf 1968.     

Delayed visual loss after pars plana vitrectomy for retained lens fragments

PURPOSE: To report visual results and postoperative complications in patients undergoing vitrectomy for retained lens fragments. METHODS: Retrospective, noncomparative, interventional case series of 42 consecutive patients undergoing vitrectomy for retained lens fragments by a single surgeon, all with a minimum of 6 months' follow-up. The main outcome measurement was best corrected visual acuity at 3 months and at final follow-up visit. RESULTS: Although 67% of eyes achieved a postoperative visual acuity of 20/40 or better at 3 months, 17% had events during follow-up that resulted in loss of vision to less than 20/40. Final best corrected visual acuity 20/40 or better was achieved in 50% of eyes. Retinal detachment occurred in 17%, and 21% of eyes required long-term therapy for glaucoma. CONCLUSION: Patients undergoing vitrectomy for retained lens fragments often develop delayed visual loss. Long-term surveillance is necessary in these patients.