The influence of the atrial natriuretic factor on venous tone in man

To assess the effect of the human atrial natriuretic factor (ANF) in vivo on human veins, a series of investigations was done on the dorsal hand vein of 11 healthy volunteers (ten men, one woman), aged from 25 to 49 years. In the case of intact veins the human ANF effect was evaluated by the "venoconstriction" test; on veins constricted by a reflex sympathetic discharge, the ANF effect was evaluated by the test of "venous reflexes", and on veins constricted with serotonin and angiotensin II by the "preconstriction" test. The results were expressed in venoconstrictive units (VCU). ANF was injected into the vein under study in increasing bolus doses (from 50 pg to 500 ng). The results indicate that this peptide did not affect either intact veins or these constricted by sympathetic discharge. On veins preconstricted with serotonin, ANF had a slight, statistically insignificant effect (848.57 +/- 378.67 VCU 30 sec before, compared to 670.00 +/- 460.25 VCU 30 sec after the injection of 50 pg; n = 7; p greater than 0.05), up to a maximal local dose of 500 ng. The same was true for the vein preconstricted with angiotensin II. It is concluded that the human atrial natriuretic factor has no significant influence on peripheral venous tone in man.     

Prion Protein-Specific Antibodies-Development,Modes of Action and Therapeutics Application

Prion diseases or Transmissible Spongiform Encephalopathies (TSEs) are lethal neurodegenerative disorders involving the misfolding of the host encoded cellular prion protein, PrP^C. This physiological form of the protein is expressed throughout the body, and it reaches the highest levels in the central nervous system where the pathology occurs. The conversion into the pathogenic isoform denoted as prion or PrP^Sc is the key event in prion disorders. Prominent candidates for the treatment of prion diseases are antibodies and their derivatives. Anti-PrP^C antibodies are able to clear PrP^Sc from cell culture of infected cells. Furthermore, application of anti-PrP^C antibodies suppresses prion replication in experimental animal models. Major drawbacks of immunotherapy are immune tolerance, the risks of neurotoxic side effects, limited ability of compounds to cross the blood-brain barrier and their unfavorable pharmacokinetic. The focus of this review is to recapitulate the current understanding of the molecular mechanisms for antibody mediated anti-prion activity. Although relevant for designing immunotherapeutic tools, the characterization of key antibody parameters shaping the molecular mechanism of the PrP^C to PrP^Sc conversion remains elusive. Moreover, this review illustrates the various attempts towards the development of anti-PrP antibody compounds and discusses therapeutic candidates that modulate PrP expression.     

Lumbar drainage for control of raised cerebrospinal fluid pressure in cryptococcal meningitis: case report and review

Raised intracranial pressure in the absence of ventricular dilatation is common in cryptococcal meningitis and associated with increased mortality. We report the case of a patient with HIV-associated cryptococcal meningitis, who developed increasing CSF pressure and visual impairment on therapy despite serial lumbar punctures. Insertion of a temporary lumbar drain controlled the opening pressure and resulted in full visual recovery. The advantages and necessary precautions with this approach are reviewed, and alternative protocols for the use of lumbar drains discussed.     

Toxicity of Amphotericin B Deoxycholate-Based Induction Therapy in Patients with HIV-Associated Cryptococcal Meningitis

Amphotericin B deoxycholate (AmBd) is the recommended induction treatment for HIV-associated cryptococcal meningitis (CM). Its use is hampered by toxicities that include electrolyte abnormalities, nephrotoxicity, and anemia. Protocols to minimize toxicity are applied inconsistently. In a clinical trial cohort of AmBd-based CM induction treatment, a standardized protocol of preemptive hydration and electrolyte supplementation was applied. Changes in blood counts, electrolyte levels, and creatinine levels over 14 days were analyzed in relation to the AmBd dose, treatment duration (short course of 5 to 7 days or standard course of 14 days), addition of flucytosine (5FC), and outcome. In the 368 patients studied, the hemoglobin levels dropped by a mean of 1.5 g/dl (95% confidence interval [CI], 1.0 to 1.9 g/dl) following 7 days of AmBd and by a mean of 2.3 g/dl (95% CI, 1.1 to 3.6 g/dl) after 14 days. Serum creatinine levels increased by 37 μmol/liter (95% CI, 30 to 45 μmol/liter) by day 7 and by 49 μmol/liter (95% CI, 35 to 64μmol/liter) by day 14 of AmBd treatment. Overall, 33% of patients developed grade III/IV anemia, 5.6% developed grade III hypokalemia, 9.5% had creatinine levels that exceeded 220 μmol, and 6% discontinued AmBd prematurely. The addition of 5FC was associated with a slight increase in anemia but not neutropenia. Laboratory abnormalities stabilized or reversed during the second week in patients on short-course induction. Grade III/IV anemia (adjusted odds ratio [aOR], 2.2; 95% CI, 1.1 to 4.3; P = 0.028) and nephrotoxicity (aOR, 4.5; 95% CI, 1.8 to 11; P = 0.001) were risk factors for 10-week mortality. In summary, routine intravenous saline hydration and preemptive electrolyte replacement during AmBd-based induction regimens for HIV-associated CM minimized the incidence of hypokalemia and nephrotoxicity. Anemia remained a concerning adverse effect. The addition of flucytosine was not associated with increased neutropenia. Shorter AmBd courses were less toxic, with rapid reversibility.     

Free wall rupture (FWR) in patients with acute ST-elevation myocardial infarction (STEMI) receiving fibrinolytic therapy (FT): a 7-year prospective study

Previous studies have shown a paradoxical increase in early mortality in older patients (>70 years) with acute STEMI treated with fibrinolytic therapy (FT), which has been attributed to the development of free wall rupture (FWR). Our aim was to assess occurrence of FWR in STEMI patients receiving FT. In this 7-year prospective study, data from 1701 consecutive patients were obtained. We analyzed predictors of the in-hospital mortality in patients > 70 years old. The independent contribution of several variables to overall mortality and FWR development was assessed using multiple logistic regression analyses. The mortality of entire cohort was 18% (306/1701). Diabetes mellitus, anterior infarction, smoking, female gender and hypercholesterolemia were independent predictors of in-hospital mortality. FT was given to 18% of all patients (304/1701) of which 13% died (39/304). FWR was 18.4-times more often in patients who received FT. Among patients younger than 70 years who received FT there was no FWR, while in patients ≥70 years of age FWR was found in almost half of the deceased (30/68; 44%). Application of FT in STEMI patients is not associated with higher mortality, but significantly increases number of FWR, especially in patients over 70 years of age.     

Impact of Fabric Construction on Adsorption and Spreading of Liquid Contaminations

A contamination on a textile material is defined as an undesirable, local formation that deviates in appearance from the rest of the material. In this paper the relationship between the shape and surface of liquid contaminations and the firmness factor of woven fabric is investigated. The interdependence of constructional and structural parameters of raw and bleached cotton fabrics were analysed. The results show that selected contaminations are distributed differently, primarily depending on the construction characteristics of the fabric, type of contamination and hydrophilicity of cotton fabric.     

Expression of Hsp70 in kidney cells exposed to ochratoxin A

Ochratoxin A (OTA) is a possible etiological agent of endemic nephropathy, a chronic renal disease with high prevalence in limited geographic areas. Ochratoxicosis has many characteristics of different pathological states in which heat shock proteins (Hsps) are usually induced. The most inducible heat shock proteins belong to the Hsp70 family. We determined the level of expression of Hsp70 by the Western blot analysis in kidneys of rats treated with low doses of OTA and in LLC-PK1 and MDCK cells exposed to OTA. Estimation of cell viability and release of lactate dehydrogenase (LDH) confirmed the toxic effects of OTA on cultured cells. OTA affects the relative distribution of two Hsp70 isoforms (68-kDa and 74-kDa isoforms), but does not change total amount of Hsp70 in rat kidney. No changes in the Hsp70 level were detected in LLC-PK1 and MDCK cells treated with OTA, although the cells were seriously injured, as was seen from the reduced cell viability and increased release of LDH. Both cell lines were capable of having Hsp70 induced following a heat shock. However, exposure of the cells to OTA before the heat shock challenge prevented Hsp70 induction. Results of the study show that OTA does not induce Hsp70 in rat kidney or in cultured kidney cells. The absence of Hsp70 protective effects in the cells and tissues might be a possible explanation for the cumulative destructive effects of OTA and a silent onset of endemic nephropathy in humans and of OTA-induced experimental nephrotoxicity in animals.