Montelukast jest skutecznym lekiem w zapobieganiu zespołowi hiperstymulacji jajników: badania eksperymentalne

Objectives: To determine the efficacy of montelukast in comparison with cabergoline in the prevention of ovarian hyperstimulation syndrome (OHSS) in rats. Material and methods: An experimental OHSS model was formed in 35 female Wistar rats. Rats (22 days old) were randomized into 5 groups, each containing 7 animals. The control group received no therapy; the mild OHSS group was administered pregnant mare serum gonadotropin (PMSG) 10 IU for 4 days, hCG 10 IU on the 5th day; the severe OHSS group received PMSG 10 IU for 4 days, hCG 30 IU on the 5th day. The montelukast group: received montelukast 10 mg/kg/day and the cabergoline group was administered cabergoline 100μg/kg/day via oral gavage for 6 days (days 22–27), in addition to those of severe OHSS. All groups were sacrificed on 28th day. Body weight, ovarian diameter and weight, vascular permeability, vascular endothelial growth factor (VEGF), semiquantitative VEGF receptor-1, and VEGF receptor-2 (VEGFR-2) immunohistochemistry were evaluated. Results: Ovarian diameter and VEGF expression were significantly lower in the montelukast and cabergoline groups than in the severe OHSS group. While montelukast was more effective in limiting vascular permeability in the severe OHSS, cabergoline was superior to montelukast with respect to the limiting effect on increased body weight and VEGFR-2 expression. Conclusions: The VEGF/VEGFR-2 interaction plays an important role in OHSS pathogenesis. Montelukast limits VEGF expression, and cabergoline reduces both VEGF and VEGFR-2 expressions; they are both effective therapies for the prevention of severe OHSS.Cel: Ocena skuteczności montelukastu w porównaniu z kabergoliną w zapobieganiu zespołowi hiperstymulacji jajników (OHSS) u szczurów. Materiał i metoda: Model doświadczalny OHSS stanowiło 35szczurów rasy Wistar, płci żeńskiej. Szczury (22 dniowe) podzielono na 5 grup, każda zawierająca 7 zwierząt. Grupa kontrolna nie otrzymała żadnej terapii. Grupa z łagodnym OHSS otrzymała gonadotropinę z surowicy ciężarnych klaczy (PMSG) w ilości 10IU przez 4 dni, hCG 10IU w 5 dniu, grupa z ciężkim OHSS otrzymała PMSG 10IU przez 4 dni, hCG 30IU w 5 dniu. Grupa z montelukastem otrzymała montelukast w dawce 10mg/kg/dzień a grupa z kabergoliną otrzymała kabergolinę 100μg/kg/dzień przez doustny zgłębnik przez 6 dni (dni 22-27). Wszystkie zwierzęta zabito w 28 dniu. Oceniono masę ciała, wymiar i wagę jajników, przepuszczalność naczyń, czynnik wzrostu śródbłonka naczyń (VEGF) oraz w immunohistochemii półilościowo receptor – 1 VEGF i receptor-2 VEGF. Wyniki: Wymiar jajnika oraz ekspresja VEGF były istotnie niższe w grupach z monelukastem i kabergoliną niż w grupie z ciężkim OHSS. Podczas gdy montelukast był bardziej skuteczny w ograniczaniu przepuszczalności śródbłonków w ciężkim OHSS, to kabergolina okazała się lepsza od montelukastu po uwzględnieniu ograniczającego efektu zwiększonej masy ciała i ekspresji VEGFR-2. Wnioski: Wzajemne oddziaływanie VEGF/VEGFR-2 odgrywa istotną role w patogenezie OHSS. Montelukast ogranicza ekspresję VEGF, a kabergolina zmniejsza zarówno ekspresję VEGF jak i VEGFR-2; obie terapie są skuteczne w zapobieganiu ciężkiemu OHSS

The Role of Parafibromin, Galectin-3, HBME-1, and Ki-67 in the Differential Diagnosis of Parathyroid Tumors

Objectives: Parathyroid carcinoma (PC) is a rare parathyroid tumor compared to parathyroid adenoma (PA) and atypical parathyroid adenoma (APA). Recent studies have suggested parafibromin has a role in the differential diagnosis of parathyroid tumors. We sought to determine the role of parafibromin as well as galectin-3, Ki-67, and HBME-1 as diagnostic markers in the differential diagnosis of parathyroid tumors. Methods: A total of 92 cases diagnosed with PA, APA, or PC at Sifa University and Private Ege Pathology Laboratory between 2006–2012 were included in the study. Parafibromin (microarray), galectin-3, Ki-67, and HBME-1 were evaluated using immunohistochemistry in all parathyroid tumors. Results: Eighty-four cases were diagnosed with PA, six with APA, and two with PC. The study group consisted of 82 females and 10 males. Their mean age was 50.9 years, and the mean tumor diameter was 1.97 cm. Parafibromin was negative in the two PC cases but positive in all APA and PA cases. Positivity was observed with galectin-3 in 17 adenoma cases, three atypical adenomas, and two carcinoma cases. Positivity with HBME-1 was found in 26 PA cases and one PC case. Parafibromin and galectin-3 expression was significant between the three tumor groups but not for HBME-1 expression. Parafibromin expression increased in PA whereas galectin-3 expression decreased. A statistical significance was found between the three tumor groups according to the Ki-67 score (p=0.010). Additionally, the Ki-67 proliferation index was under 1% in PAs. Conclusion: The number of PCs in our series was small so our data mostly reflects the immunohistochemical characteristics of PAs. Parafibromin expression, galectin-3 negativity, and a Ki-67 proliferation index under 1% were estimated as beneficial in the differential diagnosis of difficult parathyroid tumors