Acid ribonuclease and alkaline ribonuclease isoenzymes in plasma of patients with decreased glomerular filtration rate.

Removal of low molecular weight proteins from plasma by kidneys depends on glomerular filtration rate (GFR), protein-glomerular membrane electric charge, steric interactions and a number of functionally active nephrons present in the kidneys. There is a well documented relationship between the concentration of low molecular weight proteins in plasma and GFR value in patients with impaired renal function. Accumulation of low molecular weight proteins in plasma along with a decrease in GFR value may in the long run enhance formation of protein tissue deposits known as various forms of amyloidosis. In this paper we present studies on plasma concentrations of acid leukocyte-type ribonuclease (RNase) and alkaline pancreatic-type RNase and GFR value in 54 patients with renal failure. RNase isoenzymes' activities were assayed by measuring their enzyme activities manifested as ability to decompose yeast RNA and assay of digestion products' concentration by spectrophotometry. The studies show that decreasing filtration rate produces an increase in serum activities of both acid and alkaline RNases, which is proportional to the logarithm of GFR value. However, the increase rate vs. GFR value is by four times higher for acid RNase than for alkaline RNase. Acid RNase in human plasma is mostly of leukocytic origin and differs from pancreatic-type alkaline RNase, which is of pancreatic origin. The obtained results may suggest that leukocyte originating proteins essentially contribute to low molecular weight protein accumulation in plasma of patients with chronic renal insufficiency.     

The efficacy and safety of once-weekly and once-fortnightly subcutaneous epoetin beta in peritoneal dialysis patients with chronic renal anaemia.

BACKGROUND: Reducing the dosage frequency of subcutaneous epoetin in peritoneal dialysis (PD) patients is convenient and should improve patient satisfaction and, possibly, compliance. We investigated if a weekly dosage of epoetin beta in PD patients safely maintained haemoglobin (Hb) concentrations equivalent to those obtained with previous twice- or thrice-weekly administration. In addition, we investigated if a fortnightly dosage of epoetin beta was safe and as effective as previous weekly administration. METHODS: After a 4 week run-in period, PD patients were switched to either weekly or fortnightly epoetin beta administration, depending on their previous treatment schedules, for 25 weeks. RESULTS: The per-protocol cohort included 128 patients, of whom 54 received epoetin beta once weekly and 74 once fortnightly. The mean change in Hb concentration from baseline over weeks 13-25 and the 90% confidence intervals (CIs) remained within the target range (10-12 g/dl) and specified equivalence (+/-0.75 g/dl) limits in the weekly (-0.34 g/dl; 90% CI: -0.14 to -0.54 g/dl) and fortnightly (-0.39 g/dl; 90% CI: -0.24 to -0.55 g/dl) cohorts. The mean change from baseline in the epoetin beta dose was 1.4 IU/kg/week (90% CI: -3.8 to 6.6 IU/kg/week; 2%) in the weekly cohort and 4.4 IU/kg/week (90% CI: 1.7-7.2 IU/kg/week; 13%) in the fortnightly cohort. Both treatment regimens were well tolerated. CONCLUSIONS: In stable PD patients switched from twice- or thrice-weekly to weekly epoetin beta treatment, Hb concentrations could be maintained within the specified range over 25 weeks without significant change in their mean epoetin beta doses. In patients switched from weekly to fortnightly treatment, Hb concentrations could also be maintained over 25 weeks. There was a small increase in the mean dose during this period, but >/=50% of patients could be maintained without dose increase. Reducing dosage frequency may improve compliance in PD patients who self-administer their epoetin.     

Analgesis and convulsant effects of guanidinoethylmercaptosuccinic acid (GEMSA) — A potent enkephalin convertase inhibitor

We studied behavioral effects of the intraventricularly and intrathecally administered guanidinoethylmercaptosuccinic acid (GEMSA) — a potent inhibitor of enkephalin convertase. When given intraventricularly in doses of 3 and 6 μg, GEMSA elicited analgesia; after doses of 12.5 and 25 μg the explosive motor behavior and convulsions occurred. Following the intrathecal administration of GEMSA (12.5, 25 and 50 μg), an increase in the tail-flick latency was observed; moreover that drug potentiated analgesic effects of the intrathecally applied Met⁵-enkephalin-Arg⁶-Phe⁷ and Met⁵-enkephalin-Arg⁶-Gly⁷-Leu⁸. All the above effects of GEMSA were significantly attenuated by naloxone. The rats subjected to chronic pain showed a weaker analgesic response to the intrathecally injected GEMSA. The ³H-GEMSA binding to enkephalin convertase in the spinal cord of these rats produced only a slight increase in K_D; besides, no changes in the enzyme activity were observed. The study shows that GEMSA has a potent pharmacological action in the central nervous system. Furthermore, this effect is partly due to the influence of GEMSA on endogenous opioid peptide systems, possibly on proenkephalin A.     

Response to anti-SARS-CoV-2 mRNA vaccines in multiple myeloma and chronic lymphocytic leukemia patients

Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients have increased morbidity and mortality rates of COVID-19 due to immunosuppression associated with the disease and ongoing therapy. The same immune impairment accompanying CLL and MM also affects suboptimal vaccine response. The study assessed the effectiveness of the humoral and T cell-mediated immunity following mRNA COVID-19 vaccination (using either BNT162b2 or mRNA-1273) in short-term (2-5 weeks after second dose) and long-term follow-up (12 weeks after vaccination). Between March and August 2021, blood samples were obtained from 62 CLL and 60 MM patients from eight different hematology departments in Poland. Total anti-RBD antibodies were detected in 37% MM patients before vaccination, increased to 91% and 94% in short- and long-term follow-up, respectively. In CLL, serological responses were detectable in 21% of patients before vaccination and increased to 45% in the short-term and 71% in long-term observation. We detected a tendency to higher frequencies of specific CD8+ T cells against SARS-CoV-2 after vaccination compared to samples before vaccination in MM patients and no changes in frequencies of specific T cells in CLL patients. Our study provides novel insights into mRNA vaccination efficacy in immunocompromised MM and CLL patients, and our findings highlight that specific CD8+ T cells against SARS-CoV-2 might be induced by vaccination but do not correlate positively with serological responses.     

The first detection of <Emphasis Type="Italic">Neospora caninum</Emphasis> DNA in the colostrum of infected cows

Limited data is available on the vertical transmission of Neospora caninum via the colostrum. The results of our previous research revealed the presence of N. caninum DNA in the milk of seropositive cows. The aim of the present work is to demonstrate parasite DNA in colostrum samples. A polymerase chain reaction using Np21 and Np6 primers was applied to DNA isolated from the colostrum sediment in order to amplify the corresponding genomic Nc-5 region. The expected 328-bp product was obtained in colostrum samples collected both on the calving day and the day after. This is the first detection of N. caninum DNA in the colostrum of seropositive cows, and these findings implicate the possibility of N. caninum transmission through the colostrum.