Effects of Oral Zafirlukast, Sildenafil, or Pirfenidone on the Formation of Postsurgical Intra-abdominal Adhesions in an Experimental Rat Model.

Introduction: Intra-abdominal adhesions' main etiology is surgical procedures that commonly require reintervention. Oral treatments with Sildenafil, Zafirlukast, and Pirfenidone have yielded decreased severity of fibrotic phenomena secondary to the introduction of foreign material. This study aimed to evaluate the efficacy of oral Zafirlukast, Sildenafil or Pirfenidone treatment on reducing or preventing intra-abdominal adhesions in an experimental rat model. Methods: Four groups, each of 10 male Wistar rats weighing 250–300 g, were used. A midline laparotomy was used to excise an area of 1.5´1.5cm and reconstructed with polypropylene mesh fixed to the abdominal wall. After 12 h, oral doses of Zafirlukast (1.25 mg/kg, group B), Sildenafil (15 mg/kg, group C), or Pirfenidone (500 mg/kg, group D) were given every day for eight days. The control group, A, received no treatment. At day nine, animals were reoperated. The implant was resected after ethically approved euthanasia and specimens were fixed in 10% formaldehyde for histopathology. Results: Control group A yielded adhesions with greater fibrovascular density and neighboring organ involvement than the other groups (P = 0.001), as well as intense inflammatory infiltrates and numerous granulomas (P = 0.04). Adhesions in group C had less fibrovascular density (P = 0.03) with decreased serosal injuries (P = 0.001) and less organ involvement. Group D had reduced adhesions without organ involvement (P < 0.01), and less inflammatory infiltrates, collagen fibers, and foreign body granulomas than groups B or C (P < 0.01). Conclusions: Oral administration of these agents did not prevent adhesions but ameliorated them. Oral Pirfenidone offered the best performance and could be recommended for human use.

Activity of Omadacycline in Rat Methicillin-Resistant Staphylococcus aureus Osteomyelitis

Omadacycline, vancomycin and rifampin as well as rifampin combination therapies were evaluated in an experimental rat model of MRSA osteomyelitis. All treatment groups had less MRSA recovered than saline-treated animals. Emergence of rifampin resistance was observed in 3 of 16 animals with rifampin monotherapy, and none with rifampin combination therapy. After treatment, the median tibial bacterial load was 6.04, 0.1, 4.81 and 5.24 log 10 cfu/g for saline-, rifampin-, vancomycin- and omadacycline-treated animals. Omadacycline or vancomycin administered with rifampin yielded no detectable MRSA. Omadacycline, administered with rifampin, deserves evaluation in humans as a potential treatment for osteomyelitis.

Jianpi Qushi Heluo Formula alleviates renal damages in Passive Hemann nephritis in rats by upregulating Parkin-mediated mitochondrial autophagy

Jianpi Qushi Heluo Formula (JQHF) is an empirical traditional Chinese medicine prescription for treating Membranous Nephropathy (MN) clinically in China. The therapeutic effect of JQHF has been reported in our previous studies. However, the exact mechanism is still unknown. In this study, by establishing an experimental rat model of MN induced by Sheep anti-rat Fx1A serum, we evaluated the effects of JQHF and Tetrandrine (TET), and Benazepril was used as a positive control. As an autophagy agonist, TET is one of the most active components in JQHF. After 4 weeks, significant kidney damage was observed in the rats in the Model group; comparatively, JQHF markedly decreased 24 h urinary protein, Total Cholesterol (TC), and increased serum total Albumin (ALB). Histology showed that JQHF caused significant improvements in glomerular hyperplasia, renal tubular damage, IgG immune complex deposition, and the ultrastructure of mitochondria in MN rats. Flow cytometry analysis showed that treatment with JQHF reduced the level of reactive oxygen species and apoptosis rate, and upregulated mitochondrial membrane potential. Western blot analysis demonstrated that JQHF could protect against mitochondrial dysfunction and apoptosis by upregulating the expression of PINK1, Mitochondrial Parkin, and LC3-II/I, downregulating the expression of Cytoplasmic Parkin, P62, Cytochrome c, and Caspase-3 in the kidneys of MN rats. From images of co-immunofluorescence, it is observed significantly increase in the co-localization of PINK1 and Parkin, as well as LC3 and mitochondria. Similarly, TET treatment significantly upregulated the mitochondrial autophagy and reduced apoptosis in rats after 4 weeks compared with the model group. Comparatively, the ability of JQHF to alleviate renal damage was significantly higher than those of Benazepril and TET. It was demonstrated that JQHF could delay pathology damage to the kidney and hold back from the progression of MN by inhibiting apoptosis and upregulating the mitochondrial autophagy by PINK1/Parkin pathways.