The influence of PTH, calcium gluconate and EDTA on the parotid saliva in the goat

1. The role of exogenous parathyroid hormone (PTH) and stimulation or inhibition of endogenous hormone release, on the parotid gland of normal and thyroparathyroidectomized (t.x.p.t.x.) goats was studied. 2. The intravenous infusion of PTH and EDTA produced a transitory rise in saliva flow rate in intact animals. In t.x.p.t.x. goats the flow of saliva decreased transiently throughout the infusion. 3. The calcium levels in parotid saliva was unchanged throughout the infusion of PTH, EDTA, calcium gluconate both alone or with propranolol, in either intact or t.x.p.t.x. animals. 4. The parathyroid hormone infusion caused an increase in salivary phosphate concentration in both intact and operated goats. The effects of PTH upon the salivary flow and concentration of P are discussed.     

Bilayer packing stress and defects in mixed dilinoleoylphosphatidylethanolamine and palmitoyloleoylphosphatidylcholine and their susceptibility to phospholipase A2

The hydrolysis of mixed dilinoleoylphosphatidylethanolamine (DiLinPE) and 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) dispersions by porcine phospholipase A2, under conditions leading to the bilayer-to-nonbilayer phase transition, has been studied. Two structurally distinct forms of the dispersions were used, multilamellar vesicles (MLV) and supercritical large unilamellar vesicles (SCLUV). In MLV, maximum free fatty acid was produced in dispersions containing 85 mol % DiLinPE. The peak in the fatty acid release is found at the onset of appearance of the nonbilayer defects reported earlier. DiLinPE was found to be preferentially hydrolyzed as compared to POPC. When cholesterol was added to the mixed DiLinPE/POPC MLV, the onset of the observable appearance of nonbilayer defects, the positions of the peaks for total hydrolysis, and the preferential hydrolysis of DiLinPE were all shifted toward lower DiLinPE concentrations. In SCLUV, where the appearance of nonbilayer structures is prevented by constraining the lipids in bilayer configuration, the hydrolysis by PLA2 increases with increasing DiLinPE as predicted from the increase in the calculated monolayer bending energy. The results are interpreted to be related to the pretransition molecular-packing stress and defects at the onset of the bilayer-to-nonbilayer transition. Results indicate that the porcine pancreatic phospholipase A2 activity is controlled by bilayer-packing stress, which may cause structural defects of the substrate, among other factors. Results also indicate a preferential localization of PE at stress-related defect regions.     

Selective Interaction Model and Photoreceptor Cell Membrane

A mathematical model is proposed in order to describe, from the thermodynamic point of view, the changes in the photoreceptorcell membrane induced by light stimuli. The phenomenologicalbackground is the increase of the fly microvillar membrane ionicconductivity as a consequence of Ca^++-Na⁺ affinity modification under light action. On the basis of the analogywith the model of protein interaction in mixed solvents, themodel is focused on the selective interaction between ionchannels gates and two ionic ligands. Three possible theoretical cases are examined.     

Differences in Sepsis Treatment and Outcomes between Public and Private Hospitals in Brazil: A Multicenter Observational Study

Background

Previous studies showed higher sepsis mortality rates in Brazil compared to other developed or developing countries. Moreover, another trial demonstrated an increased mortality rate in public hospitals compared to private hospitals in Brazil. The reasons for these findings may include delayed recognition and inadequate treatment of sepsis in public facilities. We designed this study to evaluate the factors associated with mortality in septic patients admitted to intensive care units in a network of public and private institutions.

Materials and Methods

This study is a retrospective analysis of a prospective cohort of sepsis patients in 19 private and public institutions in Brazil. We analyzed data from the original database and collected additional data to assess compliance to the treatment guidelines and to determine the time from the onset of organ dysfunction and the sepsis diagnosis by the healthcare team.

Results

A total of 396 patients were analyzed. Patients in public hospitals were younger, had a greater number of dysfunctional organs at baseline and a lower chance to have sepsis diagnosed within two hours of the onset of organ dysfunction. Private hospitals had a better compliance to lactate and blood culture sampling and maintenance of glycemic control. The multivariate analysis showed that age, disease severity at baseline and being treated at a public hospital were independent risk factors for mortality. A delay in the sepsis diagnosis of longer than two hours was associated with mortality only in the public setting.

Conclusions

We confirmed a lower sepsis mortality rate in the private hospitals of this network. Being treated in a public hospital was an independent factor for mortality. Delayed recognition of sepsis was more frequent in public institutions and this might have been associated with a higher mortality. Improving sepsis recognition and early diagnosis may be important targets in public institutions.     

Nephrology Referral and Outcomes in Critically Ill Acute Kidney Injury Patients

Background

Delayed nephrology consultation (NC) seems to be associated with worse prognosis in critically ill acute kidney injury (AKI) patients.

Design, Setting, Participants, & Measurements

The aims of this study were to analyze factors related with timing of NC and its relation with AKI patients'' outcome in intensive care units of a tertiary hospital. AKI was defined as an increase ≥50% in baseline serum creatinine (SCr). Early NC and delayed NC were defined as NC performed before and two days after AKI diagnosis day. Multivariable logistic regression and propensity scores (PS) were used to adjust for confounding and selection biases. Hospital mortality and dialysis dependence on hospital discharge were the primary outcomes.

Results

A total of 366 AKI patients were analyzed and NCs were carried out in 53.6% of the patients. Hospital mortality was 67.8% and dialysis required in 31.4% patients (115/366). Delayed NCs (34%) occurred two days after AKI diagnosis day. This group presented higher mortality (OR: 4.04/CI: 1.60–10.17) and increased dialysis dependence (OR: 3.00/CI: 1.43–6.29) on hospital discharge. Four variables were retained in the PS model for delayed NC: diuresis (1000 ml/24 h - OR: 1.92/CI: 1.27–2.90), SCr (OR: 0.49/CI: 0.32–0.75), surgical AKI (OR: 3.67/CI: 1.65–8.15), and mechanical ventilation (OR: 2.82/CI: 1.06–7.44). After correction by PS, delayed NC was still associated with higher mortality (OR: 3.39/CI: 1.24–9.29) and increased dialysis dependence (OR: 3.25/CI: 1.41–7.51). Delayed NC was associated with increased mortality either in dialyzed patients (OR: 1.54/CI: 1.35–1.78) or non-dialyzed patients (OR: 2.89/CI: 1.00–8.35).

Conclusion

Delayed NC was associated with higher mortality and increased dialysis dependence rates in critically ill AKI patients at hospital discharge. Further studies are necessary to ascertain whether this effect is due to delayed nephrology intervention or residual confounding factors.     

A novel technique to assay adducts of DNA induced by anticancer agent cis-diamminedichloroplatinum(II).

The dideoxynucleotides d(pGpG) and d(pApG) and the tetradeoxynucleotide d(CpTpApG) were synthesized in solution phase by a modified phosphotriester technique and reacted with the anticancer agent cis-diamminedichloroplatinum(II) (cisplatin). The major products were isolated by HPLC and characterized by NMR and mass spectrometry as cross-link adducts of cisplatin with the neighboring purine bases. The cross-link adducts of d(pGpG) and d(pApG) were dansylated through a 5'-phosphoramidate linkage with ethylenediammine. The labeling efficiency of the adducts was quantitative as in the case of the normal dinucleotides. The modified tetramer was digested with nuclease P1. The excised adduct was enriched by HPLC and labeled with dansyl chloride. The analysis of the postlabeled adduct by HPCL, using a fluorescence detector, detected a peak with retention time corresponding to that of the dansylated cis-Pt(NH3)2d(pApG). Cochromatography with the authentic marker confirmed the identification. The same overall procedure was used to assay calf thymus DNA exposed to cisplatin. The major adducts were identified as cis-Pt(NH3)2d(pGpG) and cis-Pt(NH3)2d(pApG). The quantitative labeling efficiency of platinum adducts combined with highly sensitive fluorescence detection technique (subfemtomol) suggests that fluorescence postlabeling assay could be a novel approach for real-time analysis of DNA modification induced by platinated drugs in biological system.     

Plakoglobin is essential for myocardial compliance but dispensable for myofibril insertion into adherens junctions

Plakoglobin (gamma-catenin), a member of the armadillo family of proteins, is a constituent of the cytoplasmic plaque of cardiac junctions and is involved in anchorage of cytoskeletal filaments to specific cadherins. Its genetic inactivation leads to an embryonic lethal phenotype due to heart dysfunction related to an impairment in the architecture of intercalated discs and in the stability of the heart tissue. To elucidate the functional consequences of the loss of plakoglobin for myofibrillar function, we monitored passive stress-strain relationship and contractility parameters of demembranated embryonic fibers. Heart fibers obtained from plakoglobin-deficient embryonic mice were significantly less compliant than were fibers from wild-type embryos. This difference was especially pronounced at lower fiber extension levels: at 120% of slack length, compliance was 2.5-fold lower in plakoglobin-deficient mice than in the corresponding wild-type group. Contractile paramenters (force per cross-section; Ca2+ sensitivity of isometric force and shortening velocity at near-zero load) were comparable in all experimental groups. Therefore, we suggest that plakoglobin is important for cardiac compliance but not necessary for the attachment of the myofibrillar apparatus to adherens junctions. Thus, we conclude that the loss of function of desmosomes and the profound disarrangement of junctional components in plakoglobin null embryos is associated with a decreased passive compliance, which may explain the ventricular rupture and consequent pericardial tamponade in embryos lacking plakoglobin.