Impact of Ultrafiltration on Back-Diffusion in Hemodialyzer

Abstract: Ultrafiltration of water from blood to dialysate decreases the rate of back–diffusion of solutes from dialysate to blood. Therefore, back–clearance ( bK ) of hemodialyzers may be expressed as bK = bK _o – bTrQ _u, where bK _o is the diffusive back–clearance, bTr is the "back–"transmittance coefficient, and Qu is the net ultrafiltration rate. A formula for bK was derived from the one–dimensional theory of hemodialyzer, and bTr was described as a function of bK _o and the Staverman reflection coefficient. The transport parameters, bK _o and bTr , for creatinine and vitamin B₁₂ were measured in two types of hemodialyzers with negligible back–filtration, using water solutions, and compared with the transport parameters, K _o and Tr , for the case of both diffusion and ultrafiltration from blood to dialysate. bK _o was in general equal to K_o. bTr was not different from Tr for creatinine whereas bTr was lower than Tr for vitamin B₁₂. Experimental values of bTr for vitamin B₁₂ were in general agreement with theoretical predictions. However, experimental values of bTr for creatinine were lower than predicted values. We conclude that the impact of ultrafiltration on back–clearance for slowly diffusing solutes is weaker than on their clearance.     

Biological effects and receptor binding affinities of new pseudononapeptide bombesin/GRP receptor antagonists with N-terminal d-Trp or d-Tpi

In an attempt to produce more powerful (effective) bombesin/GRP receptor antagonists, the d forms of Trp or Trp analog (Tpi) were introduced at position 6 in two pseudononapeptides, Leu¹³Ψ (CH₂NH)Leu¹⁴-bombesin(6-14) and Leu¹³Ψ(CH₂NH)Phe¹⁴ -bombesin (6-14). These antagonists were tested for their ability to inhibit basal and gastrin releasing peptide (GRP) (14-27)-induced amylase release from rat pancreatic acini in a superfusion assay. They were also assessed for the inhibition of ¹²⁵I-Tyr⁴ -bombesin binding to Swiss 3T3 and small cell lung carcinoma cell line H-345 and the mitogenic response of Swiss 3T3 cells induced by GRP(14-27). The peptides, when given alone, did not stimulate amylase secretion, but were able to inhibit gastrin releasing peptide (14-27)-induced amylase release. All of the antagonists showed strong binding affinities for Swiss 3T3 and H-345 cells and suppressed the GRP(14-27)-induced increase of [³H]thymidine incorporation into DNA of Swiss 3T3 cells at nanomolar concentrations. Antagonist d -Tpi⁶,Leu¹³Ψ (CH₂NH)Leu¹⁴-bombesin (6-14)(RC-3095) was slightly more potent in these assays than d -Trp⁶,Leu¹³Ψ (CH₂NH)Leu¹⁴-bombesin (6-14)(RC-3125). Nevertheless, d -Trp⁶ Leu¹³Ψ (CH₂NH)Phe¹⁴-bombesin (6-14) showed the highest binding affinity for Swiss 3T3 and H345 cells and it was the most potent inhibitor of GRP(14-27)-induced amylase secretion. This antagonist RC-3420 was particularly effective in inhibiting the growth of Swiss 3T3 cells, exhibiting an IC₅₀ value less than 1 nm . Our work indicated that the substitution of d -Trp and d -Tpi at position 6 of the pseudononapeptide bombesin analogs (Ψ^13-14), in which the Met¹⁴ residue is replaced by Leu or Phe, results in potent bombesin/GRP antagonists with improved in vivo activity.     

Transesophageal Programmed Atrial Pacing as a Method of Selecting Patients with Sick Sinus Syndrome for Permanent Atrial Pacing

Many recent studies have shown transesophageal programmed atrial pacing (TP) as a very practical, safe and convenient way for assessment of sinus node function and AV conduction. On the other hand, permanent atrial pacing is known to be superior to ventricular pacing due to arrhythmogenic and hemodynamic reasons. This is the reason why we decided to use TP as a method of choosing patients with sick sinus syndrome (SSS) for permanent atrial pacing. Sixty-three patients with symptomatic (58) and asymptomatic (5) SSS in a variety of clinical situations were examined in this way. The following electrophysiological features were examined: sinus cycle length, sinus node recovery time as well as corrected time, secondary pause after overdrive stimulation, sinoatrial conduction time, Wenckebach point, induction of supraventricular arrhythmias by S1, S2, S3 programmed stimulation and burst pacing. Patients with abnormal parameters were examined once more after intravenous atropine 0.2 mg/kg to evaluate parasympathetic component. Standard 12-lead ECG was performed in ail, and Holter monitoring in most of patients.
Twenty-six patients were candidates for permanent AAI pacing. Failures occurred in eight patients usually due to low P wave amplitude and electrode instability. Eighteen patients received AAI pacing systems: eight with brady-tachycardia syndrome, nine with brady-arrhythmia and one with sinoatrial block. In the follow-up of 5–28 months in one patient occurred high degree AV block (11°) during digitalis therapy. Reduction of doses made this block disappear. Examination of Wenckebach point and possibility of inducation of supraventricular lachyarrhythmias in cases of atrial overexcitability are particularly useful in selecting patients for AAI pacing. (PACE, Vol 11 November Part II 1988)     

First‐in‐Man Study of Dedicated Bifurcation Sirolimus‐eluting Stent: 12‐month Results of BiOSS LIM® Registry

Objectives

The aim was to assess the effectiveness and safety profile of a new dedicated bifurcation stent ‐ sirolimus‐eluting BiOSS LIM® (Balton, Poland) in 12‐month Registry.

Background

The optimal approach to coronary bifurcations treatment by percutaneous coronary intervention (PCI) has been still a subject of debate. Dedicated bifurcation stents are one of the proposed solutions.

Methods

This was the international, 3‐center registry, which enrolled patients with non‐ST‐elevation acute coronary syndrome (NSTE‐ACS) and stable angina. Provisional T‐stenting was the obligatory strategy of the treatment. Angiographic control was planned at 12 months. The primary endpoint was cumulative rate of death, myocardial infarction (MI) and target lesion revascularization (TLR) at 12 months.

Results

A total of 60 patients with coronary bifurcations were enrolled (mean age 66.4 ± 11 years, 28.3% of female). There were 21.7% of patients with NSTE‐ACS, 78.3% with hypertension, 38.3% with diabetes, 28.3% had previous MI, and 46.7% and 10% underwent prior revascularization, respectively, PCI and coronary artery bypass graft. The device success rate was 100%. Side branch was treated with an additional classical drug‐eluting stent implantation in 23.3% of cases. At 12 months, the cumulative major adverse cardiovascular events rate was 11.7%. During follow‐up (11 ± 1 months) there was 1 non‐cardiac death (1.7%), 1 non‐ST‐elevated myocardial infarction (1.7%) due to restenosis and no case of stroke or in‐stent thrombosis. Overall TLR was 8.3% (clinically driven TLR – 1.7%, angiographically driven – 6.6%). Mean late lumen loss was as follows: In main vessel – 0.35 ± 0.33 mm, in main branch – 0.34 ± 0.27 mm and in side branch – 0.18 ± 0.38 mm.

Conclusion

Dedicated bifurcation stent BiOSS® LIM proved to be feasible device, with promising safety and long‐term clinical effectiveness in the treatment of coronary bifurcation lesions, including distal left main stem stenosis. (J Interven Cardiol 2015;28:51–60)

     

Evaluation of biological activities of new LH-RH antagonists (T-series) in male and female rats

A series of new highly potent LH-RH antagonists (T-series) has been synthesized in our laboratory. Among these analogs, antagonists [Ac-d -Nal(2), d -Phe(4Cl)². d -Pal(3)³, d -Lys(A₂pr(Car)₂)⁶, d -Ala¹⁰LH-RH (T-140); [Ac-d -Nal(2)¹, d -Phe(4Cl)², d -Pal(3)³, d -Lys(A₂pr(Ac)₂)⁶, d -Ala¹⁰]LH-RH (T-148); [Ac-d -Nal(2)¹, d -Phe(4Cl)², d -Pal(3)³, d -Lys(A₂pr(For)₂)⁶, d -Ala¹⁰)]LH-RH (T-151) and [Ac-d -Nal(2)¹, d -Phe(4cl)², d -Pal(3)³, d -Lys(A₂bu(For)₂)⁶, d -Ala¹⁰]LH-RH (T-159) were the most powerful. Antagonists T-140, T-148 and T-151 produced a complete blockade of ovulation in normal cycling rats at a dose of 1.5 μg/rat and antagonist T-159 at a dose of only 0.75 μg/rat. The inhibitory effects of compounds T-148, T-151 and T-159 on gonadotropin and sex steroid secretion were investigated in male and female rats. To determine their effect on LH levels in castrated male and ovariectomized female rats, T-148, T-151 and T-159 were injected subcutaneously in doses of 0.625 and 2.5 μg/rat. Blood samples were taken at different intervals for 48 h. All three compounds at either dose caused a significant (P< 0.01) decrease in LH levels for more than 6 h. Significant (P <0.01) inhibition of LH lasted for more than 24 h following a dose of 2.5 μg sc of all 3 antagonists in both male and female rats. Serum FSH levels were also suppressed significantly for more than 48 h in castrated male rats by all three antagonists at a dose of 5 μg/rat sc. Serum testosterone levels were measured in intact male rates injected with antagonists T-148, T-151 and T-159 in doses of 50 and 100 pg sc. Both doses produced a dramatic fall in testosterone (P<0.01) to castration levels 6 h after injection. The inhibition of serum testosterone lasted for more than 48 h, but only 100 μg of T-148 maintained testosterone in the castration range for more than 48 h. Antagonists T-148, T-151 and T-159 injected at a dose of 100 μg to intact female rats reduced serum estradiol levels significantly (P<0.01) for more than 48 h, as compared to control animals. In the cutaneous anaphylactoid test (CAT), T-148, T-151 and T-159 proved to have very low histamine releasing activities. These data demonstrate a high efficacy of these new LH-RH antagonists in suppressing the pituitary-gonadal axis in male and female rats. These LH-RH antagonists could possibly be used for treatment of sex-hormone sensitive cancers and other disorders and conditions, in which a reduction in circulating sex steroids would be beneficial.     

Comparison of GH-stimulation by GH-RH(1-29)NH2 and an agmatine29 GH-RH analog,after intravenous,subcutaneous and intranasal administration and after pulmonary inhalation in rats

Many studies have shown that human GH-RH(1-29)NH₂ possesses full intrinsic activity of GH-RH(1-44)NH₂in vitro and in vivo. This investigation was performed to evaluate the efficacy of GH-RH(1-29)NH₂ given by different routes of administration in stimulating GH release in rats. In each case GH-RH(1-29)NH₂ was administered intravenously, subcutaneously, intranasally and by pulmonary inhalation at two different doses to groups of seven male rats. At a dose of 150 μg/kg GH-RH(1-29)NH₂, the magnitude of GH response was significantly higher for the pulmonary inhalation group (355 ± 33.2 ng GH/mL) than for the subcutaneous group (246 ± 36ng GH/mL) or for the intranasal group (175 ± 30ng GH/mL). The group injected intravenously with GH-RH(1-29)NH₂ at a dose of 2.5 μg/kg showed the highest response, GH levels reaching 877.2 ± 115 ng/mL. A similar pattern of responses was obtained for the superactive GH-RH(1-29) agmatine²⁹ analog, MZ–3-149, at doses that were 50 times lower. Our results indicate a high bioavailability of GH-RH(1-29)NH₂ or analog MZ-3-149 administered by a convenient pulmonary inhalation route. The GH-releasing effect of GH-RH(1-29)NH₂ or analog MZ-3-149 delivered by pulmonary inhalation is superior to subcutaneous and intranasal administration.     

Late caliceal fistula after kidney transplantation

Caliceal fistula is a rare urological complication that can occur usually shortly after kidney transplantation (KTx). The occlusion of the renal accessory artery with subsequent necrosis of the kidney pole is the most common cause of the fistula development. We report a case of a 57-year-old man with reconstruction of two accessory renal arteries by anastomosis to the side of the main artery during graft placement complicated by late caliceal fistula, managed surgically. Directly after KTx good kidney graft function (serum creatinine concentration 151 micromol/L) was observed. The patient noticed protuberance and pain in the kidney graft area 5 months later. Diagnostic imaging revealed moderate urostasis and liquid collection in the region of the lower graft pole. Administration of a contrast medium through the inserted drain visualized a fistula of a lower renal calyx and ureteric stenosis. Percutaneous drainage was applied with subsequent stop of diuresis through the urethral catheter. During the surgery, the resection of a lower kidney graft pole necrosis was performed, with the closure of caliceal fistula. Simultaneously double pigtail ureteric stent was inserted. After the next two months the pigtail catheter was removed, and neither urostasis in the kidney graft nor liquid collection in the perigraft area were observed. The exceptionality of the case is the late caliceal fistula occurrence. We may only speculate, why it happened 5 months after KTx. The thrombosis of stenosed accessory artery is the most probable cause.