Ticagrelor and Dapagliflozin Have Additive Effects in Ameliorating Diabetic Nephropathy in Mice with Type-2 Diabetes Mellitus

Cardiovascular Drugs and Therapy - Ticagrelor and dapagliflozin can suppress the activation of the NOD-like receptor 3 (NLRP3)-inflammasome and activate AMP-activated protein kinase (AMPK). The...     

Treatment of intracardiac thrombi with argatroban

Intracardiac thrombi are well known complications associated with diverse cardiac diseases and venous thromboembolism. Therapeutic recommendations like thrombolysis, surgical thrombectomy, or treatment with low molecular heparin and intravenous unfractionated heparin based on small numbers of patients or retrospective case series have failed to reach a consensus. We report on the use of argatroban, a new direct thrombin inhibitor in 4 patients with intracardiac thrombi. Therapy was effective in all patients with complete resolution of thrombi. Treatment was complicated by recurrent strokes with complete neurological recovery in one patient. Therapy of intracardiac thrombi by argatroban is safe and effective. The drug requires no dosage adjustments for age, sex, or renal impairment, including in dialysis-dependent patients. Argatroban has been found to increase predictably activated partial thromboplastin time (aPTT) and activated clotting time (ACT) in a dose-dependent manner.     

Repeated poisoning of the life partner by thallium — a case of questionable Munchausen by adult proxy syndrome with ensuing attempted murder

After the use of thallium as rat poison was banned, the knowledge about the severe and treacherous course of poisonings with this toxic metal has widely been lost. In the present case, the male victim sustained two insidious poisoning attacks in 2017 and 2020 by the perpetrator, his female life partner. In the first poisoning episode, he suffered from increasing heavy pain of the abdomen, stinging pain of both legs, persistent obstipation, hyperesthesia, and, after about 2 weeks, tuft-wise loss of hair as typical symptoms of the thallium poisoning. Within 7 weeks, he was successively examined in six hospitals with a wide variety of diagnostic methods, but a conclusive explanation of the complaints was not found. The possibility of a metal intoxication was then suggested by the perpetrator who privately arranged the analysis of a blood sample with the result of 175 µg/l thallium. Although a criminal poisoning was assumed, the perpetrator was not identified. After the victim left the perpetrator, she subtly executed a second poisoning attack with thallium sulfate (blood level 1230 µg/l after 1 day, urine level 4760 µg/l after 10 days, and hair concentrations 3.26–0.49 from proximal to distal in 9 segments). The perpetrator was sentenced to 10.5 years imprisonment for grievous bodily harm and attempted murder. Because of the behavior of the perpetrator, a Munchausen by proxy syndrome was discussed as a motivation of the first poisoning but was excluded by the psychiatric expert because of a missing antisocial personality disorder.

     

Relationship of backwash ileitis to ileal pouchitis after ileal pouch-anal anastomosis

To assess whether the presence of backwash ileitis predisposed to the subsequent development of ileal pouchitis after ileal pouch-anal anastomosis, 131 patients who had the operation were studied. Fifteen patients had nonspecific inflammation in the terminal ileum noted at the time of the operation, while 20 patients subsequently developed pouchitis. No correlation between the two conditions was found. Pouchitis developed in two of 15 patients (13 percent) with backwash ileitis and in 18 of 116 patients (16 percent) without the ileitis (P>0.05). Among the 20 patients (16 percent) without the ileitis (P>0.05). Among the 20 patients with pouchitis only two (10 percent) had had previous backwash ileitis. It is concluded that the presence of backwash ileitis does not predispose to later development of pouchitis, and so does not contraindicate use of the inflammed terminal ileum for construction of the ileal pouch and anastomosis. Supported by the Swedish Medical Research Council Grant 7093, Pfimmer/Meda, Virding Fortia Foundation, and the Mayo Foundation.     

On the accumulation of alloxan in the pancreatic β-cells

Summary Autoradiographic studies revealed that the radioactivity in the pancreatic islets was higher than in any other mouse tissue after intravenous injections of tracer doses of ¹⁴C-2-alloxan. The concentration of radioactivity in the endocrine pancreas concerned a great majority of the cells indicating that at least cells were involved. The uptake of the radioisotope in the pancreatic islets was considerably reduced when the small amounts of ¹⁴C-2-alloxan were complemented with carrier to bring up the total dose to the diabetogenic level or were proceeded by higher doses of non-radioactive alloxan. There was no accumulation of radioactivity in the islets after injection of the non-diabetogenic conversion products of ¹⁴C-2-alloxan obtained in an alkaline medium and only insignificant uptake was noted after exposure of the radioactive alloxan to the reactive SH-groups of glutathione. The absence of significant radioactivity in the islets of growing animals after tracer doses of ¹⁴C-2-alloxan suggests that the ability of the cells to concentrate alloxan is confined to the adult age.This study was supported by grants from the Swedish Medical Research Council, the United States Public Health Service (AM-05759-05) and Knut and Alice Wallenbergs Stiftelse.     

Coagulation disorders in patients with cirrhosis and severe sepsis

Background: In patients with cirrhosis, severe sepsis may stimulate the extrinsic coagulation pathway resulting in thrombin generation and fibrin formation. Aims: To compare 23 patients with severe sepsis to 13 infected patients without severe sepsis and 18 patients without infection. Methods: Zymogen forms of clotting factors involved in the extrinsic pathway (i.e., factors VII+X, V, prothrombin), and the presence of soluble fibrin were assessed. Results: Zymogen forms of clotting factors were significantly lower, while Child–Pugh score and the proportion of patients with soluble fibrin were higher in the severe‐sepsis group than in the other groups. Decreased zymogen levels were independently correlated with an elevated Child–Pugh score and the presence of severe sepsis. In the severe‐sepsis group, after adjustment for the severity of cirrhosis, decreased zymogen levels were associated with significant increases in the relative risk ratios of in‐hospital death. Conclusions: Cirrhotic patients with severe sepsis have decreased blood levels of zymogen forms of factors VII+X, V, and prothrombin, which may be due not only to the severity of cirrhosis but also, at least in part, to the consumption of these zymogens by the extrinsic coagulation pathway.