Influence of the geographical origin on substance concentrations in herring as basis for dietary exposure assessments.

Previous investigations on agricultural products showed that geographical origin influences concentrations of selected undesirable substances and ultimately dietary exposure assessment. This could also be relevant for fish from different catching areas, as substance concentrations have been found to vary between catching areas. Herring was chosen as an example. Norwegian and German data on consumption and substance concentrations were considered. To investigate if concentrations of substances are different in Norway and Germany, monitoring data between 2012 and 2017 were used. Norway provided data of commercial catching areas from the Norwegian Spring Spawning (NSS) herring stock, while Germany had market data available. Concentrations of cadmium, mercury and selenium tended to be higher in herring from Norway, while lead concentrations were higher in Germany. Polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/Fs), dioxin-like polychlorinated biphenyls (DL-PCBs) and non-dioxin-like PCBs (NDL-PCBs) tended to have higher concentrations in Germany, while perfluorinated alkylated substances (PFAS) were mostly below quantifiable levels in the two countries. These differences could be attributed to different herring stocks available on the market in Germany and Norway. Country-specific data on consumption and substance concentrations give a basis for a refined exposure assessment covering both the Norwegian and the German situation. This is of special importance if European risk assessments are carried out combining concentration data recorded in several countries without taking origin into account.

[Clinical polymorphism of myasthenia gravis beginning with isolated ocular symptoms; a five years retrospective analysis]. / Polymorphisme clinique de la myasthénie à point de départ oculaire; analyse rétrospective sur cinq ans.

INTRODUCTION: myasthenia gravis is a neuromuscular junction disorder that can jeopardize the patient's life and has a high clinical polymorphism that makes it difficult to diagnose. PATIENTS AND METHODS: after reviewing the disease physiology, its clinical symptoms, and the different means to diagnose and treat it, we present a 15-patient series that we cared for at the Rothschild ophthalmologic foundation from 2002 to 2007 for myasthenia gravis that began with isolated ocular symptoms, so as to highlight the clinical diversity of this pathology. RESULTS: when the disease was diagnosed, 11 patients out of 15 had a ptosis with diplopia, two had an isolated ptosis, and two had isolated diplopia. After investigations, we discovered that three patients had a malignant thymoma and one had thymic hyperplasia. An autoimmune disease association was found in two patients: the first one had Hashimoto thyroiditis and the second one developed optical neuromyelitis a few years after his myasthenia gravis. Only three patients secondarily developed a generalized myasthenia gravis. DISCUSSION: our series of patients has a low disease generalization rate in comparison with the published data in the medical literature, indicating that two-thirds of patients with ocular myasthenia gravis should develop generalized myasthenia gravis within approximately 2 years after the beginning of their illness. This could be explained by the early consultation of these patients and the common prescription of an immunosuppressive therapy, reducing the risk of secondarily generalized myasthenia gravis according to some studies. CONCLUSION: despite the small number of patients, this study underlines the clinical polymorphism of ocular myasthenia gravis and the risks it may cause. Close collaboration between ophthalmologists and neurologists is needed to ensure good care for these patients.

[Bilateral papilledema: prospective study of fifty patients]. / OEdèmes papillaires bilatéraux : étude prospective de 50 patients.

In this prospective study, we report fifty consecutive cases of bilateral papilledema without neurosurgical or obvious ophthalmologic etiology, referred to our institution between January 2005 and March 2007. Lumbar puncture with opening CSF pressure measurement distinguished two groups of patients: Group 1 (n=39) with and Group 2 (n=11) without intracranial hypertension. In Group 1, 9/39 patients presented secondary intracranial hypertension mainly due to cerebral venous thrombosis. In 30 patients, after complete investigations, a diagnosis of idiopathic intracranial hypertension was made: as commonly reported, patients were predominantly overweight (96.7% with body mass index>25kg/m2) young (mean age=27.6 years) and women (96.7%). Eleven patients with intracranial hypertension had no headaches. In Group 2, the most common diagnosis was bilateral non-arteritic anterior ischemic optic neuropathy, but rare causes have been identified.

Ratio of serum gamma-GT/ALT rather than ISDR variability is predictive for initial virological response to IFN-alpha in chronic HCV infection.

Chronic hepatitis C virus (HCV) infection in humans is treated at present with interferon (IFN)-alpha. Because the proportion of patients responding to therapy with sustained or even just with transient elimination of viral RNA is low, several potential prognostic parameters have been evaluated to predict the outcome of the therapy. The present study aimed to prove the validity of a predictive parameter described previously for initial virological response, namely the ratio of serum gamma-glutamyltransferase/alanine transaminase (gamma-GT/ALT) activity in connection with virus genotypes 1a, 1b, and 3a, prospectively and to compare the predictive value of these combined parameters with amino acid variability within the interferon sensitivity determining region (ISDR). The prospective analysis confirmed previous data on the predictive value of the serum gamma-GT/ALT ratio. Concerning ISDR variability, the majority of ISDR sequences obtained from the mostly nonresponding type 1b-infected individuals (23/28) resembled nonmutant types (27/ 28). Isolates from type 3a-infected patients responding to therapy in the majority of cases (13/ 20) exclusively resembled nonmutant types when compared with databank type 3a sequences, but were mutant when compared with the prototype sequence HCV-J. However, the initial virological responsiveness among both type 1b- and type 3a-infected patients did not correlate to ISDR variability. In contrast, virological responsiveness was closely related to serum gamma-GT/ALT ratio. The data are not necessarily contrary to the concept that the number of amino acid exchanges within the ISDR compared with the prototype HCV-J sequence is related to some extent to IFN-alpha sensitivity. The ratio of serum gamma-GT/ALT in combination with HCV genotype, however, was found to be a more reliable and stringent predictive parameter.

Renal response to hemorrhage in dogs with subacute biliary obstruction.

In the present study, we tested the hemodynamic and renal response of 15 sham-operated dogs and 15 dogs with subacute (5-9 days) biliary obstruction to either acute or more chronic hemorrhage. All studies were conducted on sedated but unanaesthetized animals. Both groups were comparable before blood withdrawal with respect to central hemodynamics and renal perfusion. Serum bilirubin was 0.70 +/- 0.09 mg/dL for control dogs and 8.25 +/- 0.14 for experimental dogs (P less than 0.05). In the acute protocol, nine control and seven jaundiced dogs were bled over a period of 30-40 min to lower blood pressure by 19.1 and 19.5%, respectively. Blood volumes required to achieve this drop were 21.3 and 20.05 mL/kg, respectively (P greater than 0.05). Cardiac output declined by an equivalent value for each group and glomerular filtration rate and clearance of p-aminohippurate remained unchanged from control values. In six control and eight experimental dogs, 500 mL of blood was withdrawn over 5 days. Although blood pressure and cardiac output declined for each group by an equivalent amount, renal perfusion remained unchanged for each group from control values. We conclude that acute or chronic hemorrhage of modest degree does not predispose to acute renal insufficiency in dogs with subacute biliary obstruction.

Effects of bile and bile salt infusions on renal function in dogs.

A previous study in dogs indicated that 4 h of acute biliary obstruction was associated with an increment in the glomerular filtration rate (GFR), renal perfusion, and urinary sodium excretion. These effects could also be transmitted to a "recipient" dog following 2 h of cross circulation. In this study we examined the possible role of bile and bile products in reproducing these effects. The i.v. infusion of 15 mL of undiluted gallbladder bile produced a marked diuresis and natriuresis, while arterial pressure and GFR declined. Bile diluted as much as 1/100 in isotonic saline could produce an effect when infused intravenously. When bile diluted to 1/250 was infused into th left renal artery at 0.5 mL/min, a diuretic and natriuretic response was obtained. GFR and renal blood flow declined with more concentrated solutions, though blood pressure remained normal. Dialysis of bile, or prior incubation with cholestyramine or plasma, failed to uncover a renal vasodilator effect. Following the first two procedures, the diuretic properties of infused bile were lost. The infusion of small amounts of synthetic bile salts (taurocholate or glycocholate) into the left renal artery caused marked increments in urinary sodium excretion without any change in renal hemodynamics. The infusion of bilirubin was without effect on renal function. Taurine and glycine, the amino acids present in the conjugated bile acids, were injected i.v. Both caused marked diuresis and natriuresis, but only glycine increased GFR and renal perfusion. The plasma levels of these substances, however, were unchanged following 4 h of acute biliary obstruction. We conclude that while bile salts probably cause the diuresis of biliary obstruction, the mechanism for the increase in GFR has not yet been identified.

Action of renal vasodilators in dogs following acute biliary obstruction.

The renal vasodilator properties of six endogenous substances were tested before and 4 hr after ligation of the common bile duct. Two substances, acetylcholine and a glucocorticoid, retained their vasodilator properties at a fixed dose following acute biliary obstruction. Dopamine was still able to increase glomerular filtration rate and renal blood flow, but demonstrated an attenuated response. Several other agents, glucagon, glycine, and bradykinin, lost their renal vasodilator actions at the dosages employed. For these latter three compounds, control studies using sham-obstructed dogs and identical waiting periods demonstrated no loss of vasoactive effect. When the order of experimental protocol was reversed, i.e., acute biliary obstruction followed by a 4-hr period without obstruction, the same phenomenon was observed. When dogs were tested 5 days following biliary obstruction, glycine, glucagon, dopamine, and dexamethasone all failed to raise either GFR or renal perfusion. The infusion of bile or dialyzed bile, but not bile salts or bilirubin, also caused the failure of glucagon, glycine, and bradykinin to exert a renal vasoactive effect. Dogs with 4 hr of biliary obstruction appeared to react normally to the pressor effects of noradrenaline and angiotensin II and to the diuretic effects of iv furosemide. The obstruction of the bile ducts with percolation of bile constituents into the circulation appears to alter the sensitivity of the renal vasculature to certain endogenous vasoactive agents.

Renal perfusion in dogs with experimental hepatic cirrhosis: role of prostaglandins.

Increased renal production of prostaglandins are thought to be important for the maintenance of kidney blood flow in advanced cirrhosis. In alert, unanesthetized dogs with chronic cirrhosis and ascites, produced by bile duct ligation, we measured inulin and p-aminohippurate (PAH) clearance before and after the intravenous administration of 2 mg/kg indomethacin, an inhibitor of prostaglandin production. Inulin and PAH clearance declined by 42 and 43%, respectively. This decline in renal perfusion was not associated with changes in blood pressure or cardiac output. If portal hypertension was prevented by creating an end-side portacaval anastomosis at the time of bile duct ligation, indomethacin was without effect on renal perfusion whether or not the dog had ascites. If ascites was completely mobilized in cirrhotic dogs with portal venous hypertension with the aid of a LeVeen valve, indomethacin depressed inulin and PAH clearance as usual during the steady-state period once all ascites had been removed. An attempt was made to determine some of the factors mediating the apparent increase in renal prostaglandin synthesis by administering various pharmacological antagonists. The inhibition of angiotensin effect with saralasin and the inhibition of kallikrein with aprotinin prevented the usual indomethacin effect. It is concluded that portal hypertension, but not a "sick liver per se, in cirrhosis activates the renin-angiotensin system to both produce renal vasoconstriction and stimulate prostaglandin synthesis, thereby normalizing renal perfusion. Renal kallikrein also appears to play a role, probably by augmenting renin release.

Suitability of commercial control sera for the quality control of activity determination of alkaline phosphatase.

The suitability of thirteen commercially available control sera for measuring alkaline phosphatase (EC 3.1.3.1; orthophosphoric acid monoester phosphohydrolase, ALP) activity in human serum was tested. Apart from differences in ALP activity observed in some reconstituted commercial sera, the behaviour of control materials towards experimental variables such as the nature and concentration of the substrate, pH and type of buffer (or PO4-acceptor) together with the composition of the isoenzymes present in human serum highlights the problems and difficulties if commercial materials are to be used as control sera. The half-saturation constants in control sera were in all cases smaller than those of ALP isoenzymes from bone and liver. The shape of substrate activity curves and the pH optimum in most of control sera differed from that of human serum. The discrepant kinetic data of control materials and human serum may mask or suggest changes relevant to commercial quality control serum but not to samples of human serum.

Suitability of commercial enzyme control sera for the quality control of activity determinations of L-aspartate aminotransferase and L-alanine aminotransferase in human serum.

Details of a systematic approach to suitability testing of commercial control sera are given for substrate optimized L-aspartate aminotransferase and L-alanine aminotransferase methods at 37 degrees C. Their acceptability for control purposes of standardized methods depends on: (1) the range of control values in relation to borderline values, (2) stability, (3) aspect, clarity, (4) NADH consumption in preincubation time, (5) blank activities, (6) kinetic data as half saturation constants and saturation curves, (7) influence of effectors, (8) isoenzyme pattern. These evaluation criteria are proposed for suitability testing. The term "representativeness" should be introduced as a special criterion for main characteristics of control materials. The authors want to point out the close connection with standardization of methods.

Influence of auxiliary enzymes on the spectrophotometric measurement of alanine aminotransferase and aspartate aminotransferase activities.

We investigated the enzyme activity of the blank in the spectrophotometric determination of the aminotransferase activities and aspartate aminotransferase activity. 6 lactate dehydrogenase and 3 malate dehydrogenase preparations from different manufactures and from different organs showed additional and contaminating activity. The additional activity depends upon the 2-oxoglutarate concentration. The contaminating activity is caused by alanine aminotransferase and aspartate aminotransferase in the auxiliary enzymes. We propose that exact definitions must be given for the auxiliary enzymes in the recommendations of standard determinations for enzyme activities.