Effect of protein load on kidney functions in patients with chronic glomerulonephritis

AIM: To study changes in renal function in response to protein loads in patients with chronic glomerulonephritis (CGN) who have normal renal function and initial uremia. MATERIAL AND METHODS: 63 CGN patients were divided into two groups: 40 patients of group 1 (17 males, 23 females, age 16-53 years, plasma creatinine-Pcr < 0.132 mmol/l); 23 patients of group 2 (10 males, 13 females, age 18-57 years, Pcr > 0.132 mmol/l). Renal functional reserve (RFR) was assessed with oral soa isolate SUPRO 760 test (protein Techn. Int., USA), 1.0 g of protein per 1 kg of ideal body mass. By three 2-h clearance periods measurements were made of RFR, absolute and fractional excretion, concentration indices and clearances of creatinine, urea, electrolytes, osmolality. All the parameters were referred to the standard body surface. RESULTS: RFR was intact in 14 patients of group 1 and 10 patients of group 2. In CGN without uremia with intact RFR, maximal Pcr corresponded to the highest values of minute diuresis and sharp increase of urea excretion, osmotically active substances. In CGN patients with uremia and intact RFR, development of hyperfiltration was accompanied with a significant rise in Pcr, minute diuresis, absolute excretion of urea and osmotically active substances. The rise in the latter two was much less active in CGN if RFR was absent. Multiple stepwise regression analysis showed that RFR intactness depends primarily on baseline values of absolute excretion of urea and osmotically active substances. CONCLUSION: A reverse relationship exists between absolute excretion of urea, osmotically active substances and the degree of SKF in response to protein load in CGN patients both in intact nitrogen-excreting function and uremia. It is suggested that urea may be involved in regulation of intraglomerular hemodynamics by means of effect on tubular-glomerular feedback mechanism.     

From PET detectors to PET scanners

This review describes the properties of available and emerging radiation detector and read-out technologies and discusses how they may affect PET scanner performance. After a general introduction, there is a section in which the physical properties of several different detector scintillators are compared. This is followed by a discussion of recent advances in read-out electronics. Finally, the physical performance of the several commercial PET scanners is summarized.     

Mycalosides B-I,eight new spermostatic steroid oligoglycosides from the sponge Mycale laxissima

New steroidal oligoglycosides mycalosides B-I (2-9) have been isolated from the polar extract of the Caribbean sponge Mycale laxissima, and their structures have been elucidated by 1D and 2D NMR ((1)H, (13)C, DEPT, COSY-45, COSY-RCT, HSQC, HMBC, and NOESY spectra) and MALDI-TOF mass spectrometry. Mycalosides B (2) and C (3) were shown to be 27- and 28-nor derivatives of the previously known tetraoside mycaloside A (1). Mycaloside D (4) differs from 1 only in the presence of an additional acetyl group in the carbohydrate moiety. Mycaloside E (5) was structurally identified as a 28-nor-4-dehydroxy derivative of 1. Mycalosides F-H (6-8), differing from each other by the structures of their side chains and nonacetylated (7, 8) or acetylated (6) tetrasaccharide carbohydrate moieties, have new 5(6)-unsaturated 3 beta,4 beta,21-trihydroxy-15-keto-steroidal aglycons. Mycaloside I (9) is a tetraoside of a new 7,24(28)-diunsaturated 3beta,15 beta,29-trihydroxystigmastane aglycon. It was established that the total fraction of the mycalosides as well as mycalosides A (1) and G (7) inhibit the fertilization of eggs by sperm of the sea urchin Strongylocentrotus nudus preincubated with these compounds.     

Free radicals potentiate the negative dromotropic effect of adenosine in guinea pig isolated heart

OBJECTIVE: Adenosine is released during myocardial ischaemia and delays atrioventricular nodal (AV) conduction. We hypothesized that free radicals present during reperfusion potentiate the negative dromotropic effect of adenosine on the AV node. METHODS AND RESULTS: Guinea pig hearts were prepared using the Langendorff technique, paced (200 beats/min), and instrumented to measure the atrium-to-His bundle (A-H) interval, an index of AV nodal conduction time. Adenosine (2 microM) prolonged the A-H interval by 5.7 +/- 0.5 ms from a control value of 35.7 +/- 1.3 ms. (n = 10, P < 0.05). In the absence of adenosine, the superoxide (O2-) generator pyrogallol (20 microM) did not affect the A-H interval (0.7 +/- 0.2 ms prolongation, n = 10). However, concurrent infusion of adenosine (2 microM) and pyrogallol (20 microM) lengthened the A-H interval by 11.0 +/- 0.8 ms from control (n = 10, P < 0.001). This A-H interval prolongation was reversed by cyclopentyl-1,3-dipropylxanthine (100 nM), a selective A1-adenosine receptor antagonist (P<0.001, n = 5). Similarly, A-H interval prolongation was decreased to 4.3 +/- 0.4 ms when NG-methyl-L-arginine (100 microM), a nitric oxide (NO) synthase inhibitor, was infused (n = 4). The superoxide scavenger superoxide dismutase (200 U/ml) also diminished the A-H interval prolongation to 7.1 +/- 0.6 ms (n = 4, P < 0.001). Ba2+ ( 100 microM), a blocker of the adenosine-induced inward potassium current (I(K,ADO)), did not significantly affect this potentiation (13.0 +/- 0.8 and 10.8 +/- 0.7 ms greater than control A-H interval in the absence and presence of Ba2+, respectively, n = 4). CONCLUSIONS: Superoxides and adenosine delay AV nodal conduction in a synergistic manner via a NO-dependent mechanism involving an I(K,ADO)-independent component. This phenomenon may contribute to the genesis of reperfusion arrhythmias.     

The influence of anticonvulsant and antioxidant drugs on nitric oxide level and lipid peroxidation in the rat brain during penthylenetetrazole-induced epileptiform model seizures

Nitric oxide (NO) generation in the brain cortex of Wistar rats was measured by direct method of electron paramagnetic resonance (EPR) spectroscopy. Dramatic (fivefold) elevation of NO production was found during penthylenetetrazole (PTZ)-induced epileptiform seizures. The level of secondary products of lipid peroxidation (LPO; thiobarbituric acid reactive substances, TBARS) was also significantly increased in the cerebral cortex of rats with PTZ-evoked seizures. The effects of anticonvulsant drugs phenobarbital, lamotrigine, phenazepam, as well as antioxidant substances alpha-tocopherol and novel original Russian synthetic drug mexidol (2-ethyl-6-methyl-3-oxypiridine succinate), were investigated. All the substances studied significantly decreased seizure manifestations and partially prevented both enhancement of NO generation and increase in TBARS formation. Mexidol and phenobarbital were found to be the most effective in the preventing of PTZ-induced seizures among all the substances studied. The data obtained support our speculation that neuroprotective action of mexidol may correlate with its ability to inhibit not only excessive reactive oxygen species (ROS) formation but also NO generation. While the molecular mechanism underlying action of mexidol and phenobarbital still remains unclear, it is likely that the effect of these drugs on NO production is contributing to their neuroprotective action. It might be concluded that both the suppression of seizure-induced NO generation and LPO enhancement may be involved in the mechanism of action of antiepileptic drugs.     

Course of pulmonary hypertension in patients operated for rheumatic mitral heart disease

AIM: To study changes in pulmonary hypertension in patients with isolated mitral valvular defects of rheumatic etiology after surgical correction and in the early postoperative period. MATERIALS AND METHODS: Central hemodynamics in heart chamber probing before operation and intraoperatively were measured in 98 patients with rheumatic mitral defects (41 males, 57 females, mean age 39.5 +/- 8.74). Manometry before and after the defect correction, intraoperative catheterization (cath. Swan-Ganz) for hemodynamics 24-h follow-up were made. RESULTS: After valvular defect correction 90(91%) patients had residual pulmonary hypertension, stage II-III in 41%. CONCLUSION: Patients operated for rheumatic heart disease complicated by pulmonary hypertension often suffer from residual pulmonary hypertension. This requires pharmacological correction.     

Tumor-targeted liposomes: doxorubicin-loaded long-circulating liposomes modified with anti-cancer antibody.

Commercially available doxorubicin-loaded long-circulating liposomes (Doxil, Alza Pharmaceuticals) were modified with the monoclonal nucleosome (NS)-specific 2C5 antibody (mAb 2C5) that recognizes a broad variety of tumors via the tumor cell surface-bound NSs. For incorporation into liposomes, mAb 2C5 was modified with poly(ethylene glycol)-phosphatidyl ethanolamine conjugate (PEG-PE) with the free PEG terminus activated with the p-nitrophenylcarbonyl group (pNP-PEG-PE). Derivatives of mAb 2C5 containing a variable number of PEG-PE residues (10-32) per protein molecule were prepared with a reasonably good preservation of the antibody specific activity even at the highest degree of modification. PEG-PE-modified antibody quantitatively incorporated into the liposomal membrane of doxorubicin-loaded liposomes with a loss of not more than 20% of the encapsulated doxorubicin. 2C5-targeted Doxil liposomes acquired the ability to recognize NSs and specifically bind to various tumor cells. Doxorubicin-loaded long-circulating liposomes modified with the mAb 2C5 kill various tumor cells in vitro with the efficiency higher than non-targeted doxorubicin-loaded liposomes.