Ágnes Janovszky

Methane biogenesis during sodium azide-induced chemical hypoxia in rats.

Previous studies demonstrated methane generation in aerobic cells. Our aims were to investigate the methanogenic features of sodium azide (NaN(3))-induced chemical hypoxia in the whole animal and to study the effects of l-α-glycerylphosphorylcholine (GPC) on endogenous methane production and inflammatory events as indicators of a NaN(3)-elicited mitochondrial dysfunction. Group 1 of Sprague-Dawley rats served as the sham-operated control; in group 2, the animals were treated with NaN(3) (14 mg·kg(-1)·day(-1) sc) for 8 days. In group 3, the chronic NaN(3) administration was supplemented with daily oral GPC treatment. Group 4 served as an oral antibiotic-treated control (rifaximin, 10 mg·kg(-1)·day(-1)) targeting the intestinal bacterial flora, while group 5 received this antibiotic in parallel with NaN(3) treatment. The whole body methane production of the rats was measured by means of a newly developed method based on photoacoustic spectroscopy, the microcirculation of the liver was observed by intravital videomicroscopy, and structural changes were assessed via in vivo fluorescent confocal laser-scanning microscopy. NaN(3) administration induced a significant inflammatory reaction and methane generation independently of the methanogenic flora. After 8 days, the hepatic microcirculation was disturbed and the ATP content was decreased, without major structural damage. Methane generation, the hepatic microcirculatory changes, and the increased tissue myeloperoxidase and xanthine oxidoreductase activities were reduced by GPC treatment. In conclusion, the results suggest that methane production in mammals is connected with hypoxic events associated with a mitochondrial dysfunction. GPC is protective against the inflammatory consequences of a hypoxic reaction that might involve cellular or mitochondrial methane generation.

The role of pancreatic ductal secretion in protection against acute pancreatitis in mice

Objectives:A common potentially fatal disease of the pancreas is acute pancreatitis, for which there is no treatment. Most studies of this disorder focus on the damage to acinar cells since they are assumed to be the primary target of multiple stressors affecting the pancreas. However, increasing evidence suggests that the ducts may also have a crucial role in induction of the disease. To test this hypothesis, we sought to determine the specific role of the duct in the induction of acute pancreatitis using well-established disease models and mice with deletion of the Na+/H+ exchanger regulatory factor-1 that have selectively impaired ductal function. Design:Randomized animal study. Setting:Animal research laboratory. Subjects:Wild-type and Na+/H+ exchanger regulatory factor-1 knockout mice. Interventions:Acute necrotizing pancreatitis was induced by i.p. administration of cerulein or by intraductal administration of sodium taurocholate. The pancreatic expression of Na+/H+ exchanger regulatory factor-1 and cystic fibrosis transmembrane conductance regulator (a key player in the control of ductal secretion) was analyzed by immunohistochemistry. In vivo pancreatic ductal secretion was studied in anesthetized mice. Functions of pancreatic acinar and ductal cells as well as inflammatory cells were analyzed in vitro. Measurements and Main Results:Deletion of Na+/H+ exchanger regulatory factor-1 resulted in gross mislocalization of cystic fibrosis transmembrane conductance regulator, causing marked reduction in pancreatic ductal fluid and bicarbonate secretion. Importantly, deletion of Na+/H+ exchanger regulatory factor-1 had no deleterious effect on functions of acinar and inflammatory cells. Deletion of Na+/H+ exchanger regulatory factor-1, which specifically impaired ductal function, increased the severity of acute pancreatitis in the two mouse models tested. Conclusions:Our findings provide the first direct evidence for the crucial role of ductal secretion in protecting the pancreas from acute pancreatitis and strongly suggest that improved ductal function should be an important modality in prevention and treatment of the disease.

A Novel Method for In Vivo Visualization of the Microcirculation of the Mandibular Periosteum in Rats

The periosteum plays an important role in bone physiology, but observation of its microcirculation is greatly limited by methodological constraints at certain anatomical locations. This study was conducted to develop a microsurgical procedure which provides access to the mandibular periosteum in rats.

The periosteal microcirculation in health and disease: An update on clinical significance

Apart from its nutritive functions, the periosteum critically affects bone regeneration via its stem/osteoprogenitor cell content. Normal healing after bone fractures, trauma-orthopedic interventions and invasive dental procedures is critically linked to the reestablishment of the periosteal microcirculation, but the reconstruction, replacement or repair of lost tissues may also be performed with autologous periosteum. Besides the initiation of cell differentiation during bone repair and remodeling processes, the periosteum together with the endosteum plays significant roles in the pathogenesis of both hormone-related and trauma-induced osteoporotic alterations in the bone metabolism. Nevertheless, the axial bones, and in particular the jawbones, and the appendicular bones display differences not only in their blood supply and fracture healing characteristics, but also in respect of the development of osteoporosis and their reactions to treatment modalities (i.e. bisphosphonates). These reactions may also be linked to the differences in periosteal microcirculatory reactions. The present overview summarizes the relevant data of microcirculatory studies focusing on the periosteal reactions in different anatomical locations together with the optimal background methodologies, study models and the most significant observations.

Estrogen-dependent efficacy of limb ischemic preconditioning in female rats†

Our aim was to examine the effects of ischemic preconditioning (IPC) on the local periosteal and systemic inflammatory consequences of hindlimb ischemia‐reperfusion (IR) in Sprague–Dawley rats with chronic estrogen deficiency (13 weeks after ovariectomy, OVX) in the presence and absence of chronic 17beta‐estradiol supplementation (E2, 20 µg kg−1, 5 days/week for 5 weeks); sham‐operated (non‐OVX) animals served as controls. As assessed by intravital fluorescence microscopy, rolling and the firm adhesion of polymorphonuclear neutrophil leukocytes (PMNs) gave similar results in the Sham + IR and OVX + IR groups in the tibial periosteal microcirculation during the 3‐h reperfusion period after a 60‐min tourniquet ischemia. Postischemic increases in periosteal PMN adhesion and PMN‐derived adhesion molecule CD11b expressions, however, were significantly reduced by IPC (two cycles of 10′/10′) in Sham animals, but not in OVX animals; neither plasma free radical levels (as measured by chemiluminescence), nor TNF‐alpha release was affected by IPC. E2 supplementation in OVX animals restored the IPC‐related microcirculatory integrity and PMN‐derived CD11b levels, and TNF‐alpha and free radical levels were reduced by IPC only with E2. An enhanced estrogen receptor beta expression could also be demonstrated after E2 in the periosteum. Overall, the beneficial periosteal microcirculatory effects of limb IPC are lost in chronic estrogen deficiency, but they can be restored by E2 supplementation. This suggests that the presence of endogenous estrogen is a necessary facilitating factor of the anti‐inflammatory protection provided by limb IPC in females. The IPC‐independent effects of E2 on inflammatory reactions should also be taken into account in this model.

Surgical Management of Progressive Hemifacial Atrophy With De-Epithelialized Profunda Artery Perforator Flap: A Case Report

Progressive hemifacial atrophy (PHA) is a rare disorder characterized by slow, unilateral atrophy of the soft tissues and bones of the craniofacial region. The defect becomes more pronounced with age, leading to esthetic and functional deficits. However, the proper timing and method of surgical reconstruction are still debated. The correction of this defect markedly influencing the quality of life of the patient can be achieved with less invasive to more invasive surgical approaches. A 21-year-old female patient with hemifacial atrophy and extensive alopecia presented to our clinic. Considering the body type and the expectations of the patient, a profunda artery perforator flap was applied for the reconstruction and esthetic improvement of the facial region. The facial asymmetry attenuated after the reconvalescence period. This case shows that in the up-to-date surgical treatment of severe PHA, the use of microvascular free flaps may provide a better approach when trying to achieve an acceptable esthetic result. This is the first time that a profunda artery perforator flap was used to restore facial asymmetry caused by PHA.

An anterolateral thigh chimeric flap for dynamic facial and esthetic reconstruction after oncological surgery in the maxillofacial region: a case report

BackgroundThe surgical management of malignant tumors in the head and neck region often leads to functional and esthetic defects that impair the quality of life of the patients. Reconstruction can be solved with prostheses in these cases, but various types of microsurgical free flaps can provide a better clinical outcome.Case presentationIn this case report, the tumor and parts of the involved facial muscles and nerve were excised surgically from a 42-year-old patient after a third relapse of basal cell carcinoma in the left midface. The tissue defect was reconstructed with an anterolateral thigh chimeric type I fascio-myocutaneous flap, where the facial palsy was restored with a segmental branch of the femoral nerve and the involved mouth corner elevator muscles for the segmented vastus lateralis muscle. The 6-month follow-up revealed a good esthetic outcome, the soft tissue defect reconstruction with good functional activity of the reconstructed facial nerve and with acceptable mimic movements. There has been no subsequent recurrence.ConclusionsIt is concluded that the chimeric type I anterolateral fascio-myocutaneous free flap can offer a good option for the esthetic and functional reconstruction of an extensive tissue defect in the maxillofacial region.

Current approaches for early detection and treatment of medication-related osteonecrosis of jaw

Owing to the increased life expectancy, the incidence of rheumatoid disorders and oncologic cases with bone metastasis has dramatically increased. Despite the beneficial effects of the applied antiresorptive and antiangiogenic drugs (e.g. bisphosphonates), serious side effects such as jaw osteonecrosis may also develop. The aim of the authors was to summarize present knowledge about the possibilities of prevention and treatment in medication-related osteonecrosis of the jaw. Based on literature data, currently used detection methods for medication-related osteonecrosis of the jaw (including their advantages and limitations) are summarized. In addition, novel trends of surgical and adjuvant therapeutic approaches are also reviewed. The authors conclude that possibilities of prevention and efficacy of therapeutic interventions in this disorder are still limited possibly due to an incomplete knowledge of the underlying pathomechanism. An interdisciplinary cooperation for prevention and attentive monitoring in order to decrease the incidence of iatrogenic oral and maxillofacial complications seems to be particularly important.