Effect of selected derivatives of histamine H3 receptor antagonists on the remodeling of peritoneal adipose tissue in animal binge eating disorder

Otyłość jest to choroba o podłożu zapalnym. Jest ona spowodowana nadmiernym gromadzeniem się tkanki tłuszczowej. Od dawna trwają poszukiwania skutecznego i bezpiecznego leku przeciwko otyłości. Ostatnio uwagę zwrócono na antagonistów receptora H3 histaminowego.Cel: Celem niniejszej pracy była ocena aktywności wybranych pochodnych receptora H3 histaminowego w tkance tłuszczowej zwierząt z rozwijającym się zespołem nadmiernego objadania się.Materiał i metody: Do przeprowadzonej analizy pobrano tkankę tłuszczową otrzewnową od szczurów rasy Wistar. Zwierzęta podzielono na 6 grup badawczych: kontrolę standardową, kontrolę z otyłością (dieta wysokokaloryczna) oraz grupy B+N, KSK60, KSK73 oraz KSK74 (dieta wysokokaloryczna + 10 mg/kg m.c. danego związku). Preparaty wybarwiono metodą Massona oraz przeprowadzono reakcję immunohistochemiczną. Następnie preparaty poddano analizie mikroskopowej. Oceniano gęstość numeryczną adipocytów, ich średnią wielkość, nasilenie stanu zapalnego oraz immunoreaktywność interleukiny 6. Wyniki poddano analizie statystycznej.Wyniki: W otyłości wywołanej dietą wysokokaloryczną tkanka tłuszczowa otrzewnowa charakteryzowała się większymi adipocytami w porównaniu do tkanki tłuszczowej kontroli standardowej (p<0,000). Stan zapalny został intensywniej wyrażony w grupie KO w stosunku do kontroli standardowej (p<0,05). Tylko związek KSK60, spośród badanych związków, nie wpływał normalizująco na tkankę tłuszczową otrzewnową w otyłości, natomiast związki KSK73 oraz KSK74 wykazały tendencję do wzrostu liczby adipocytów bez ich znaczącej hipertrofii.Obesity is an inflammatory disease. It is caused by too much fat build-up. The search for an effective and safe anti-obesity drug has been going on for a long time. Recently, attention has been focused on histamine H3 receptor antagonists.Aim: The aim was to evaluate the activity of selected derivatives of the histamine H3 receptor in the adipose tissue of animals developing binge eating disorder.Material and methods: Peritoneal adipose tissue from Wistar rats was collected for the analysis. The animals were divided into 6 research groups: standard control, obesity control (high-calorie diet) and groups B+N, KSK60, KSK73 and KSK74 (high-calorie diet + 10 mg / kg b.w. of a given compound). The slides were stained by Masson's method and an immunohistochemical reaction was performed. Then the preparations were subjected to microscopic analysis. The numerical density of adipocytes, their mean size, the intensity of inflammation and the immunoreactivity of interleukin 6 were assessed. The results were analyzed statistically.Results: In obesity induced by a high calorie diet, the peritoneal adipose tissue was characterized by larger adipocytes compared to the adipose tissue of the standard control (p <0.000). Inflammation was more intensively expressed in the KO group as compared to the standard control (p <0.05). Only the compound KSK60, did not normalize the peritoneal adipose tissue in obesity, while the compounds KSK73 and KSK74 showed a tendency to increase the number of adipocytes without their significant hypertrophy

First report of a <i>Staphylococcus caprae</i> isolated from middle ear fluid of an infant with recurrent acute otitis media

Staphylococcus caprae was originally isolated from goat milk. This uncommon coagulase-negative staphylococcus, usually associated with animals, has only infrequently been detected in human clinical specimens. Its association with acute otitis media has not been demonstrated so far. The study reports the first isolation of S. caprae from the middle ear fluid of a 12-month-old infant with recurrent, bilateral acute otitis media. Biochemical traits and susceptibility pattern of the isolated strain are also presente

First report of a <i>Staphylococcus caprae</i> isolated from middle ear fluid of an infant with recurrent acute otitis media

Staphylococcus caprae was originally isolated from goat milk. This uncommon coagulase-negative staphylococcus, usually associated with animals, has only infrequently been detected in human clinical specimens. Its association with acute otitis media has not been demonstrated so far. The study reports the first isolation of S. caprae from the middle ear fluid of a 12-month-old infant with recurrent, bilateral acute otitis media. Biochemical traits and susceptibility pattern of the isolated strain are also presente

KSK-74 : dual histamine H3 and Sigma-2 receptor ligand with anti-obesity potential

Many studies involving compounds that enhance histamine release, such as histamine H(3) receptor (H(3)R) antagonists, have shown efficacy in inhibiting weight gain, but none have passed clinical trials. As part of the search for H(3) receptor ligands that have additional properties, the aim of this study is to evaluate the activity in the reduction in weight gain in a rat model of excessive eating, as well as the impact on selected metabolic parameters, and the number and size of adipocytes of two new H(3)R antagonists, KSK-60 and KSK-74, which also exert a significant affinity at the sigma-2 receptor. Compounds KSK-60 and KSK-74 are homologues and the elongation of the distal part of the molecule resulted in an approximate two-fold reduction in affinity at H(3)R, but simultaneously an almost two-fold increase in affinity at the sigma-2 receptor. Animals fed palatable feed and receiving KSK-60 or KSK-74 both at 10 mg/kg b.w. gained significantly less weight than animals in the control obese group. Moreover, KSK-74 significantly compensated for metabolic disturbances that accompany obesity, such as an increase in plasma triglyceride, resistin, and leptin levels; improved glucose tolerance; and protected experimental animals against adipocyte hypertrophy. Furthermore, KSK-74 inhibited the development of inflammation in obesity-exposed adipose tissue. The in vivo pharmacological activity of the tested ligands appears to correlate with the affinity at the sigma-2 receptors; however, the explanation of this phenomenon requires further and extended research