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Judul Asli : Electronic Prinsiples Jilid Ix, 394 p. : il.; 24 c

Antibiotic penetration into bone and joints: An updated review

Treatment of bone and joint infections can be challenging as antibiotics should penetrate through the rigid bone structure and into the synovial space. Several pharmacokinetic studies measured the extent of penetration of different antibiotics into bone and joint tissues. This review discusses the results of these studies and compares them with minimum inhibitory concentrations (MIC) of common pathogens implicated in bone and joint infections in order to determine which antibiotics may have a greater potential in the treatment of such infections. Clinical outcomes were also evaluated as data were available. More than 30 antibiotics were evaluated. Overall, most antibiotics, including amoxicillin, piperacillin/tazobactam, cloxacillin, cephalosporins, carbapenems, aztreonam, aminoglycosides, fluoroquinolones, doxycycline, vancomycin, linezolid, daptomycin, clindamycin, trimethoprim/sulfamethoxazole, fosfomycin, rifampin, dalbavancin, and oritavancin, showed good penetration into bone and joint tissues reaching concentrations exceeding the MIC90 and/or MIC breakpoints of common bone and joint infections pathogens. Few exceptions include penicillin and metronidazole which showed a lower than optimum penetration into bones, and the latter as well as flucloxacillin had poor profiles in terms of joint space penetration. Of note, studies on joint space penetration were fewer than studies on bone tissue penetration. Although clinical studies in osteomyelitis and septic arthritis are not available for all of the evaluated antibiotics, these pharmacokinetic results indicate that agents with good penetration profiles would have a potential utilization in such infections. Keywords: Antibiotics, Bone, Cortical, Cancellous, Penetration, Synovial fluid, Pharmacokinetic

In Vitro Cytotoxic Evaluation and Apoptotic Effects of Datura innoxia Grown in Saudi Arabia and Phytochemical Analysis

Datura innoxia is an important species of Solanaceae family with several purposes in folk medicine. This study intends to explore the cytotoxic effect of D. innoxia on various cancer cell proliferation. D. innoxia ethanolic extract’s effect on the progression of the cell cycle and the induction of apoptosis were investigated by flow cytometry. Further, real-time PCR was employed to confirm apoptosis initiation. In addition, active phytochemicals of D. innoxia was identified by gas chromatography–mass spectroscopy (GC-MS). The cell viability study revealed that the ethanolic extract of D. innoxia demonstrated potent cytotoxicity, with an IC50 value of 10 μg/mL against LoVo colon cancer cells. Cell cycle staining with propidium iodide revealed that D. innoxia treatment leads to cell accumulation in the sub-G1 phase. Using the Annexin V-FITC/PI assay, the ethanolic extract was found to cause a dose-dependent increase in early and late apoptosis when compared to control cells. Apoptosis as the mode of cell death was also confirmed by the increased expression of p53, bax and caspase-8, -9, and -3 along with downregulation of Bcl-2. GC-MS analysis displayed that 3,5-Dihydroxybenzoic acid (16.53%), heneicosyl formate (14.14%), 2,3-dimethyl-3-pentanol (12.89%), 2-hydroxy-4-methyl pentanoic acid (5.19%) were the main phytoconstituents. These findings conclude that D. innoxia causes cell death through apoptosis, suggesting more attention should be paid to further exploration of the active components from D. innoxia responsible for the observed activities