Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR4/NF-kB pathway

BACKGROUND: Neuroinflammation is the response of the central nervous system to events that interfere with tissue homeostasis and represents a common denominator in virtually all neurological diseases. Activation of microglia, the principal immune effector cells of the brain, contributes to neuronal injury by release of neurotoxic products. Toll-like receptor 4 (TLR4), expressed on the surface of microglia, plays an important role in mediating lipopolysaccharide (LPS)-induced microglia activation and inflammatory responses. We have previously shown that curcumin and some of its analogues harboring an α,β-unsaturated 1,3-diketone moiety, able to coordinate the magnesium ion, can interfere with LPS-mediated TLR4-myeloid differentiation protein-2 (MD-2) signaling. Fluoroquinolone (FQ) antibiotics are compounds that contain a keto-carbonyl group that binds divalent ions, including magnesium. In addition to their antimicrobial activity, FQs are endowed with immunomodulatory properties, but the mechanism underlying their anti-inflammatory activity remains to be defined. The aim of the current study was to elucidate the molecular mechanism of these compounds in the TLR4/NF-κB inflammatory signaling pathway. METHODS: The putative binding mode of five FQs [ciprofloxacin (CPFX), levofloxacin (LVFX), moxifloxacin, ofloxacin, and delafloxacin] to TLR4-MD-2 was determined using molecular docking simulations. The effect of CPFX and LVFX on LPS-induced release of IL-1β and TNF-α and NF-κB activation was investigated in primary microglia by ELISA and fluorescence staining. The interaction of CPFX and LVFX with TLR4-MD-2 complex was assessed by immunoprecipitation followed by Western blotting using Ba/F3 cells. RESULTS: CPFX and LVFX bound to the hydrophobic region of the MD-2 pocket and inhibited LPS-induced secretion of pro-inflammatory cytokines and activation of NF-κB in primary microglia. Furthermore, these FQs diminished the binding of LPS to TLR4-MD-2 complex and decreased the resulting TLR4-MD-2 dimerization in Ba/F3 cells. CONCLUSIONS: These results provide new insight into the mechanism of the anti-inflammatory activity of CPFX and LVFX, which involves, at least in part, the activation of TLR4/NF-κB signaling pathway. Our findings might facilitate the development of new molecules directed at the TLR4-MD-2 complex, a potential key target for controlling neuroinflammation

Cell entry of a host targeting protein of oomycetes requires gp96

This work is supported by the [European Community’s] Seventh Framework Programme [FP7/2007–2013] under grant agreement no. [238550] (L.L., J.D.-U., C.J.S., P.v.W.); BBSRC [BBE007120/1, BB/J018333/1 and BB/G012075/1] (F.T., I.d.B., C.J.S., S.W., P.v.W.); Newton Global Partnership Award [BB/N005058/1] (F.T., P.v.W.), the University of Aberdeen (A.D.T., T.R., C.J.S., P.v.W.) and Deutsche Forschungsgemeinschaft [CRC1093] (P.B., T.S.). We would like to acknowledge the Ministry of Higher Education Malaysia for funding INA. We would like to thank Brian Haas for his bioinformatics support. We would like to acknowledge Neil Gow and Johannes van den Boom for critical reading of the manuscript. We would like to acknowledge Svetlana Rezinciuc for technical help with pH-studies.Peer reviewedPublisher PD

PTH assay in the first postoperative day after thyroidectomy early predictor postoperative hypocalcemia?

BACKGROUND: The purpose of our study is to verify if PTH assay on the first postoperative day is a reliable early predictor of the onset of hypocalcemia. METHODS: Between October 1999 and May 2000, a prospective trial involved 162 patients who underwent total or near total thyroidectomy at our institute. On the basis of PTH assay on first day we divided the patients in three groups: group A 28 patients with PTH 16 pg/ml. RESULTS: In group A: 22 of 28 patients (78.5%) developed postoperative hypocalcemia and 20 (71.4%) needed replacement therapy; in group B: 14 of 34 (41.1%) had postoperative hypocalcemia and 10 (29.4%) received treatment; in group C: 23 of 100 (23%) became hypocalcemic after surgery but only 5 (5%) require calcium-vitamin therapy. A statistically significant correlation (p = 0.0017) was identified between post-operative PTH levels and lowest blood calcium values detected after surgery. The correlation between the drop in blood calcium levels after surgery and postoperative PTH (delta Ca) was statistically even more significant (p = 0.0002); the lower the postoperative PTH, the higher the absolute value of the delta Ca. CONCLUSION: The authors suggest a clinical approach and pharmacological treatment protocol based on the outcome of PTH assay on the first post-operative day; a solution that is only apparently more costly because it in fact aims to ensure a more timely recourse to blood calcium monitoring or replacement therapy and also an earlier discharge of the patient

PRIMARY HYPERPARATHYROIDISM IN PATIENTS TREATED FOR NON-MEDULLARY THYROID CARCINOMA

Abstract: The authors report three cases of primary hyperparathyroidism (HPT) in patients with differentiated thyroid carcinoma (DTC) developed a few years after initial surgical and radiometabolic treatment of DTC. The early diagnosis of HPT in these patients was made possible because of laboratory tests performed during follow-up, including the assay of serum calcium and serum phosphorus levels. Scinti-graphy using 99mTc-MIBI enabled the correct preoperative localisation of a single parathyroid adenoma in two of these patients and multiglandular pathology in the third

Incisional hernia treatment with progressive pneumoperitoneum and retromuscular prosthetic hernioplasty

BACKGROUND AND AIM: Major incisional hernias of the abdominal wall often pose a serious surgical problem. The choice between simple suture repair and mesh repair remains uncertain. METHODS: Seventy-seven patients underwent surgery to repair large abdominal incisional hernias, i.e., with parietal defects of 10 cm or more, by retromuscular prosthetic hernioplasty between 1996 and 1999. All patients were treated preoperatively by progressive pneumoperitoneum and were followed up for 2-5 years (mean 38.3 months). RESULTS: Almost all patients tolerated the pneumoperitoneum; no postoperative death occurred. Six patients developed a subcutaneous infection but none of them required removal of the mesh. Two patients (2.6%) had recurrent incisional hernia. CONCLUSIONS: This study shows that pneumoperitoneum is useful in preparing patients for incisional hernioplasty. Retromuscular mesh repair represents an appropriate surgical procedure, particularly in view of its low rate of recurrence

Incisional hernia treatment with progressive pneumoperitoneum and retromuscular prosthetic hernioplasty

Background and aim: Major incisional hernias of the abdominal wall often pose a serious surgical problem. The choice between simple suture repair and mesh repair remains uncertain. Methods: Seventy-seven patients underwent surgery to repair large abdominal incisional hernias, i.e., with parietal defects of 10 cm or more, by retromuscular prosthetic hernioplasty between 1996 and 1999. All patients were treated preoperatively by progressive pneumoperitoneum and were followed up for 2-5 years (mean 38.3 months). Results: Almost all patients tolerated the pneumoperitoneum; no postoperative death occurred. Six patients developed a subcutaneous infection but none of them required removal of the mesh. Two patients (2.6%) had recurrent incisional hernia. Conclusions: This study shows that pneumoperitoneum is useful in preparing patients for incisional hernioplasty. Retromuscular mesh repair represents an appropriate surgical procedure, particularly in view of its low rate of recurrence

PREVENTION AND TREATMENT OF INTRA- AND POST-OPERATIVE COMPLICATIONS IN THYROID SURGERY

Abstract: Frequency of complications in thyroid surgery is evaluated in a series of patients treated during a recent period lasting one year (1997). The records of 455 patients consecutively operated on were analyzed: 396 patients were affected by benign disorders and 59 by thyroid carcinoma. Total thyroidectomy was performed in 158 cases, near subtotal thyroidectomy in 94, thyroid totalization for recurrent disease in 21 and lobectomy in 182 ones. Post-operative haemorrhage, such to require surgical re-exploration of the thyroid bed, occurred in 2 patients (0.4%), both after total thyroidectomy for hyperfunctioning goiter. Recurrent laryngeal lesion has been observed in 2 patients (0.4% of all patients), both after total thyroidectomy for cervico-mediastinal goiter. Transient hypoparathyroidism occurred in 48 patients (10.5%), while definitive one in 9 (1.9%), of which 5 after total thyroidectomy, 2 after subtotal thyroidectomy and 2 after reoperation. Haemorrhage nearly always occurs in the first postoperative hours and gravity is conditioned by tracheal compression exercised by the haematoma. An aspirative drainage located in thyroid bed and a not hermetic closure of the middle line help a precocious diagnosis and sometimes avoid a surgical re-exploration. Some technical surgical devices permit to reduce the risk of inferior laryngeal nerve palsy. Hypoparathyroidism, often transient, is a complication of bilateral thyroid surgery, but unavoidable when more extensive thyroid surgery is required

Technique and results of laparoscopic adrenalectomy

The aim of this report is to evaluate the benefits of laparoscopic adrenalectomy in terms of perioperative morbidity, complications and patients recuperation. We reviewed our experience with laparoscopic adrenalectomy in 47 consecutive patients who underwent adrenalectomy over a 4-year period. We used the lateral transperitoneal approach in all cases. The indications for adrenalectomy were Conn's adenoma in 24 patients, pheochromocytoma in 11, Cushing's syndrome in 3 and incidental adrenal tumour in 9. The average duration of surgery was 130 min (range, 60-300 min) and average adrenal gland size was 3.4 cm (range, 1.2-8 cm). Conversion from laparoscopy to laparotomy was necessary in three patients (6.4%), and postoperative complications occurred in two patients. There was no mortality. Laparoscopic adrenalectomy can be considered the method of choice for managing almost all adrenal masses, because of its low morbidity and short postoperative recovery. The main difficulty is to identify the adrenal gland, so several technical procedures are suggested