Nanobiotic formulations as promising advances for combating MRSA resistance: susceptibilities and post-antibiotic effects of clindamycin,doxycycline, and linezolid

Antimicrobial activity and post-antibiotic effects (PAEs) are both important parameters in determination of the dosage regimen of antimicrobial agents. In the present study, antimicrobial activity and PAEs of clindamycin, doxycycline, linezolid, and their nanobiotic formulations were evaluated against two methicillin resistant Staphylococcus aureus clinical isolates (MRSA) encoded (MRSA-S1 and MRSA-S2). Nanobiotic formulations increased the susceptibility of MRSA isolates by 4–64 folds as compared to their conventional ones. The PAE values were determined after exposure of MRSA isolates for 1 h to 10× the MICs of the tested antibiotics. The duration of PAEs were recorded after bacterial growth in Mueller Hinton broth (MHB) free from antibiotic has been restored. The PAE values for MRSA-S1 were 2.5 h for the conventional antibiotics. However, the PAEs for nanobiotics were 4 h for both clindamycin and linezolid, while 3 h for doxycycline. For MRSA-S2, linezolid and linezolid nanobiotics PAEs were 3 h. PAEs of clindamycin and clindamycin nanobiotics were 3.75 h and 4 h, respectively. Doxycycline and doxycycline nanobiotics revealed the same PAEs patterns of 3.5 h. The findings of the current study may positively influence the pharmacodynamics of the antibiotics and consequently the dosage regimen of nanobiotics as well as on their clinical outcome.

Novel nanobiotic formulations of clindamycin, doxycycline, and linezolid were evaluated for the post-antibiotic effects against biofilm forming methicillin resistant Staphylococcus aureus (MRSA).     

Role of peritoneal ultrasonography and ultrasound-guided fine needle aspiration cytology/biopsy of extravisceral masses in the diagnosis of ascites of undetermined origin

Background and study aimsAscites may be of undetermined origin despite comprehensive study. This study aimed to assess the accuracy and safety of conventional and interventional high-frequency peritoneal ultrasound in the diagnosis of patients with ascites of unclear origin.Patients and methodsA total of 62 patients were prospectively enrolled; they underwent conventional (3.5–5 MHz) and high-frequency (6–8 MHz) transabdominal peritoneal ultrasound to suggest the nature of ascites supplemented by fine needle aspiration cytology (FNAC) of ascites and/or core biopsy of the omentum or other extra-visceral masses for final histopathologic diagnosis. Laparoscopy or laparotomy was needed if biopsy was inconclusive.ResultsUltrasound-guided procedures were diagnostic in 55 (87.7%) patients. Thirty-six (58.1%) were benign, of whom 86% had tuberculous peritonitis, 26 (41.9%) were malignant, of whom 76.9% had peritoneal metastasis. High-frequency ultrasound was able to propose ultrasonographic criteria in a trial to diagnose the nature of ascites. Our proposed ultrasonographic criteria were based on the amount and texture of ascites in addition to the omental and mesenteric features. These were able to suggest the diagnosis with 80.7% sensitivity for malignant ascites and 75% specificity for benign ascites. Moreover, histopathological examination of tissues obtained by ultrasound-guided procedures increased the sensitivity to 88.5% and the specificity to 88.9% in diagnosing malignant and benign disease, respectively, with an overall diagnostic accuracy of 88.6%. These procedures were considered to be safe as only one major (haemoperitoneum) and two minor complications (temporary ascitic fistula) were reported.ConclusionHigh-frequency peritoneal ultrasound together with the minimally invasive ultrasound-guided FNAC/biopsy of extra-visceral lesions may be considered an effective and safe tool in the diagnosis of ascites of undetermined origin.     

Impact of Calcium and Two Doses of Vitamin D on Bone Metabolism in the Elderly: A Randomized Controlled Trial

The optimal dose of vitamin D to optimize bone metabolism in the elderly is unclear. We tested the hypothesis that vitamin D, at a dose higher than recommended by the Institute of Medicine (IOM), has a beneficial effect on bone remodeling and mass. In this double‐blind trial we randomized 257 overweight elderly subjects to receive 1000 mg of elemental calcium citrate/day, and the daily equivalent of 3750 IU/day or 600 IU/day of vitamin D3 for 1 year. The subjects’ mean age was 71 ± 4 years, body mass index 30 ± 4 kg/m², 55% were women, and 222 completed the 12‐month follow‐up. Mean serum 25 hydroxyvitamin D (25OHD) was 20 ng/mL, and rose to 26 ng/mL in the low‐dose arm, and 36 ng/mL in the high‐dose arm, at 1 year (p < 0.05). Plasma parathyroid hormone, osteocalcin, and C‐terminal telopeptide (Cross Laps) levels decreased significantly by 20% to 22% in both arms, but there were no differences between the two groups for any variable, at 6 or 12 months, with the exception of serum calcitriol, which was higher in the high‐dose group at 12 months. Bone mineral density (BMD) increased significantly at the total hip and lumbar spine, but not the femoral neck, in both study arms, whereas subtotal body BMD increased in the high‐dose group only, at 1 year. However, there were no significant differences in percent change BMD between the two study arms at any skeletal site. Subjects with serum 25OHD <20 ng/mL and PTH level >76 pg/mL showed a trend for higher BMD increments at all skeletal sites, in the high‐dose group, that reached significance at the hip. Adverse events were comparable in the two study arms. This controlled trial shows little additional benefit in vitamin D supplementation at a dose exceeding the IOM recommendation of 600 IU/day on BMD and bone markers, in overweight elderly individuals. © 2017 American Society for Bone and Mineral Research.     

Polyarthritis with chondronecrosis associated with osteonecrosis, panniculitis and pancreatitis

Arthritis associated with panniculitis complicating pancreatitis is well described in the literature, usually associated with osteonecrosis. Chondronecrosis has not been reported before in association with pancreatitis. We report a patient with chronic pancreatitis who presented with polyarthritis, panniculitis, osteonecrosis, but in addition had clear evidence of chondronecrosis. We suggest that direct extension of noxious materials from nearby subchondral osteonecrotic bone lesion could be the cause of the osteonecrosis and one of the pathological mechanisms leading to arthritis in patients with pancreatitis.     

Biochemical/metabolic changes associated with hepatocellular carcinoma development in mice

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality after lung and stomach cancers. This work was undertaken to investigate some of the biochemical mediators/pathways associated with or implicated in the pathogenesis of HCC. Male albino mice were classified into two groups: normal control group and HCC group. Early stage HCC was induced by injection of diethylnitrosamine (DEN) i.p. 200 mg/kg as a single dose, and after 2 weeks, the mice were given i.p. injection of thioacetamide (TAA) 100 mg/kg twice per week for 4 weeks. Mice were left for further 2 weeks without any treatment, after which, mice were sacrificed; blood and liver samples were collected. Serum was used for determination of activities of glucose-6-phosphate dehydrogenase (G6PDH) and aldolase as well as levels of insulin-like growth factor-1 (IGF-1) and epithelial cadherin (E-cadherin). One portion of the liver was used for histopathological examination and immunohistochemical staining of the tumor suppressor p53 protein. Another portion of the liver was used for determination of citrate synthase activity. Induction of HCC in mice resulted in significant increase in G6PDH and aldolase activities, and E-cadherin level, but significant decrease in IGF-1. HCC mice group showed moderate expression of p53 protein. These results suggest that the molecular pathogenesis of HCC in mice involves reduction of serum level of IGF-1 and increased serum level of E-cadherin accompanied by dysregulation of p53 protein expression. HCC was also associated with reprogrammed metabolic profile shifted toward increased glycolysis and lipogenesis.