Rosmarinic acid affects immunological and inflammatory mediator levels and restores lung pathological features in asthmatic rats

Background: The effects of rosmarinic acid (RA) on immunological and inflammatory mediator levels in bronchoalveolar lavage fluid (BALF) as well as lung pathological changes in asthmatic rats were investigated. Methods: The levels of IFN-gama, IL-4, IFN-gama/IL-4 ratio, IgE, PLA2, and total protein (TP) in BALF and pathological changes in the lung were evaluated in control group (C), asthma group (sensitized to ovalbumin) (A), asthma groups treated with RA and dexamethasone. Results: Compared to the control group, asthmatic rats showed increased levels of IL-4, IgE, PLA2, and TP as well as all pathological scores with decreased levels of IFN-gama and IFN-gama/IL-4 ratio (P < 0.05 to P < 0.001). The levels of IL-4, IgE, PLA2, and TP significantly reduced in groups treated with all concentrations of RA compared to asthma group (P < 0.001 for all cases). IFN-gama was significantly decreased in groups treated with two lower concentrations of RA but IFN-gama/IL-4 ratio was increased in groups treated with two higher concentrations of RA compared to asthma group (P<0.05 to P < 0.001). Treatment with all doses of RA led to significant improvement in pathological scores in asthmatic animals (P < 0.05 to P < 0.001). Most measured parameters were also significantly improved in dexamethasone-treated animals (P<0.01 to P < 0.001) but IFN-gama/IL-4 ratio and the scores of interstitial fibrosis, bleeding and epithelial damage did not change in this group. Conclusion: The results indicated a preventive effect for RA on immunological and inflammatory mediators as well as lung pathological changes in asthmatic rats which were comparable or even more potent than that of dexamethasone

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Rosmarinic acid affects immunological and inflammatory mediator levels and restores lung pathological features in asthmatic rats.

BACKGROUND: The effects of rosmarinic acid (RA) on immunological and inflammatory mediator levels in bronchoalveolar lavage fluid (BALF) as well as lung pathological changes in asthmatic rats were investigated. METHODS: The levels of IFN-γ, IL-4, IFN-γ/IL-4 ratio, IgE, PLA2, and total protein (TP) in BALF and pathological changes in the lung were evaluated in control group (C), asthma group (sensitized to ovalbumin) (A), asthma groups treated with RA and dexamethasone. RESULTS: Compared to the control group, asthmatic rats showed increased levels of IL-4, IgE, PLA2, and TP as well as all pathological scores with decreased levels of IFN-γ and IFN-γ/IL-4 ratio (P<0.05 to P<0.001). The levels of IL-4, IgE, PLA2, and TP significantly reduced in groups treated with all concentrations of RA compared to asthma group (P<0.001 for all cases). IFN-γ was significantly decreased in groups treated with two lower concentrations of RA but IFN-γ/IL-4 ratio was increased in groups treated with two higher concentrations of RA compared to asthma group (P<0.05 to P<0.001). Treatment with all doses of RA led to significant improvement in pathological scores in asthmatic animals (P<0.05 to P<0.001). Most measured parameters were also significantly improved in dexamethasone-treated animals (P<0.01 to P<0.001) but IFN-γ/IL-4 ratio and the scores of interstitial fibrosis, bleeding and epithelial damage did not change in this group. CONCLUSION: The results indicated a preventive effect for RA on immunological and inflammatory mediators as well as lung pathological changes in asthmatic rats which were comparable or even more potent than that of dexamethasone.

The Effect of Allium cepa Extract on Lung Oxidant, Antioxidant, and Immunological Biomarkers in Ovalbumin-Sensitized Rats.

OBJECTIVES: To evaluate the effects of Allium cepa (A. cepa) on levels of oxidants, antioxidants, and immunological markers in bronchoalveolar lavage fluids (BALF) of sensitized rats. MATERIALS AND METHODS: Oxidant/antioxidant markers and cytokines in BALF of control rats treated with saline (group C), ovalbumin-sensitized rats (group S), rats treated with 1.25 µg/mL dexamethasone and 3 doses of A. cepa extract (35, 70, and 140 mg/kg body weight [BW]/day) (S + AC) were investigated. Comparison of the results between groups was performed using analysis of variance with the Tukey-Kramer post hoc test. RESULTS: The oxidant markers nitrogen dioxide (NO2), nitrate (NO3-), and malondialdehyde (MDA), and immunological markers interleukin (IL)-4 and immunoglobulin E (IgE) were significantly higher, but the antioxidant markers superoxide dismutase (SOD), catalase (CAT), thiol, and interferon (IFN)-γ, and the IFN-γ/IL-4 ratio were lower in sensitized rats compared to control rats (p < 0.001 to p < 0.01). Compared to group S, the levels of the following markers were significantly lower: NO2, NO3-, and IgE in groups treated with the A. cepa extract, MDA and IL-4 levels in groups treated with 70 and 140 mg/kg BW/day of the A. cepa extract, and all these markers as well as IFN-γ in rats treated with dexamethasone (p < 0.001 to p < 0.05). However, there were significantly higher levels of SOD and CAT and an increased IFN-γ/IL-4 ratio (groups treated with 70 and 140 mg/kg BW/day of the A. cepa extract), and levels of thiol and IFN-γ (group treated with 140 mg/kg BW/day of the A. cepa extract) as well as SOD, CAT, and thiol (dexamethasone-treated group) versus group S (p < 0.00 to p < 0.05). CONCLUSION: A. cepa showed antioxidant and immunomodulatory properties in sensitized rats.

Primary Charnley total hip arthroplasty: a comparison of American and Japanese cohorts followed for 10-20 years.

Primary Charnley total hip arthroplasties (THAs) followed for 10 to 20 years were compared between an American (183 sockets and 178 femoral prostheses) and a Japanese (145 sockets and 148 femoral prostheses) series, each performed by a single surgeon at a single hospital using similar techniques. The primary etiology was developmental dysplasia of the hip (70%) in the Japanese series and primary osteoarthrosis (50%) in the American series. Radiographic socket survival was inferior in the Japanese series at 4- to 11-year follow-up, which was attributed mainly to the etiologic difference. The American patients had higher levels of postoperative activity and developed more accelerated polyethylene wear, which may lead to an increased loosening rate of sockets > or = 10 years after THA. The American series had higher rates of femoral revision at > or = 9 years follow-up, which was attributed mainly to lower canal flare indices in that series.

Osteolysis after Charnley primary low-friction arthroplasty. A comparison of two matched paired groups.

We reviewed 249 consecutive Charnley primary low-friction arthroplasties in 191 patients performed by one surgeon using a transtrochanteric approach at a minimum follow-up of ten years. Of these, 37 hips in 32 patients showed osteolysis and were compared with 41 hips in 37 matched patients with no osteolysis. We assessed in each case the wear rate, stability of the prosthesis, acetabular angle, socket angle, thickness of the acetabular and femoral cement mantle, canal flare index, femoral score, stem alignment, implant:canal ratio and stem:canal ratio. We found that a high rate of wear, component instability and osteolysis were associated. Osteolysis was three times more common in men than in women. Factors which reduced osteolysis were cement mantles of 6 mm at the acetabulum and of 3 mm in all zones of the femur, a stem:canal ratio of 60% to 70% and an implant:canal ratio of over 99%. The overall incidence of osteolysis was 14.9% but when these technical criteria were met, the incidence was 5.2%. This suggests that careful technique can dramatically reduce the risk of this complication.

Interaction between lead acetate and morphine on antinociception in mice by formalin test.

1. In this study, the effects of lead acetate on two types of pain (nociception and inflammation) induced by formalin and its interactions with opioid system and morphine-induced analgesia were examined. Male albino mice weighing 22-27 g were used in the experiments. 2. To study nociception, the formalin test was selected. Morphine was administered subcutaneously 30 min before formalin injection. Lead acetate treatment was administered 90 min before any injection. Comparisons between groups were made by analysis of variance and then by Newman-Keuls test. Differences with P < or = 0.05 was considered statistically significant. 3. Different doses of morphine induced antinociception in both phases of the formalin test. Lead acetate induced non-dose-dependent nociception in the early phase and dose-dependent analgesia in the late phase. 4. Pretreatment with lead acetate antagonized the effect of morphine in the early phase. In the other hand, the effect of lead acetate in the early phase was reduced by morphine and its effect eliminated in the late phase. 5. It is concluded that lead can modulate pain response and interact with morphine-induced antinociception. Additional research to find the mechanisms of these effects are suggested.

Comparative study of total hip arthroplasty between younger and older patients.

Ten- to 20-year (average, 14 years) results of primary Charnley low friction arthroplasties performed in patients 50 years of age or younger (55 sockets and 53 femoral prostheses) were compared with those in patients older than 50 years (273 sockets and 273 femoral prostheses). The incidence of radiologic loosening of the socket, including revision cases, was higher in the younger (29.1%) than in the older patients (14.3%). The revision rate for aseptic loosening of the socket was higher in the younger (20%) than in the older group (4%). This poor performance of the socket may be attributable to the higher incidences of rheumatoid diseases and accelerated polyethylene wear in the younger patients. In contrast, only 3.8% of the femoral prostheses were radiologically loose, and none of them were revised in the younger patients. These figures were comparable with those in the older patients. Quality of structure of bone available for implant fixation may be important for the durability of the arthroplasty. It was considered inferior on the acetabular side and better on the femoral side in the younger patients than in the older. Continued use of the cemented Charnley femoral prostheses can be justified in young patients, although further research is required for the socket problem.

Trochanteric osteotomy and wire fixation: a comparison of 2 techniques.

Between 1986 and 1989, 190 patients (214 hips) with the diagnosis of osteoarthritis or posttraumatic arthritis underwent cemented Charnley total hip replacement surgeries via the biplane or single plane transtrochanteric approach. The technique of surgery was identical in every aspect except for the technique of the trochanteric osteotomy and reattachment. The results indicate that there was no significant difference in union rates between the 2 groups. Six (6.4%) patients in the biplane group and 7 (6.2%) patients in the single plane group had obvious evidence of nonunion at the 1-year evaluation. This study suggests no significant difference in union rate between a group of patients with biplane osteotomy and a closely paired group of patients with single plane osteotomy. Other equally important factors also may influence the rate of union of the trochanter in total hip arthroplasty.

Long term bone remodeling around the Charnley femoral prostheses.

Femoral bone remodeling after total hip replacement was studied by following patients who received 326 Charnley femoral prostheses for 10 to 20 years (mean, 13.3 years). The radiographic state of the bone remodeling was visually assessed and measured with a digitizer. Demineralization that started proximally and then progressed distally caused cortical thinning, which correlated with widening of the intramedullary canal, not with changes that developed in the periosteal width, and occurred in the medial femoral neck, around the proximal half of the stem, and around the distal half in 87%, 33%, and 10%, respectively. Cortical thinning around the distal half of the stem was always accompanied by proximal thinning, and extensive cortical thinning (both proximal and distal) correlated with both lower clinical scores and radiologic loosening of the femoral prosthesis. A low canal flare index of Noble, a large canal width, and a patient age of 60 years or more were risk factors for extensive cortical thinning. Accelerated polyethylene wear was related to resorption of the medial femoral neck but not to cortical thinning or radiological loosening. Cortical thickening occurred only around the distal half of the stem in 29%. These findings establish a basis for the performance of cemented femoral prostheses, and allow comparison of bone remodeling when evaluating other femoral prostheses.

Cemented revision of failed total hip arthroplasty. Survivorship analysis.

A review of 107 total hip arthroplasties performed with acrylic cement in 89 patients at Columbia-Presbyterian Medical Center by 1 surgeon from 1971 to 1990 revealed a clinical survivorship of 97% at 5 years and 76% at 10 years. The average followup was 7.7 years. Analysis of radiographs revealed a 94% success rate at 5 years and 62% at 10 years. A transtrochanteric approach was used in 99% of procedures. The 13 definite failures (12.1%) included 8 rerevisions (7.5%) and 5 failures (4.6%) pending revision. Modified Merle d'Aubigné and Postel postoperative scores increased significantly from preoperative values (pain, 2.8-5.3 points; movement, 3.2-5.2 points; function, 2.6-5.4 points). Bone grafting was required in 33% of procedures and did not affect survivorship: 24% of procedures required acetabular bone grafts; 4% femoral bone grafts; and 5% acetabular and femoral grafts. In 46% of hips, removal of the original well-fixed femoral cement and plug was deliberately incomplete. Stems of standard length were used for these partially rechannelized femurs because the old distal cement column served as a plug for the canal. Old osseointegrated polymethylmethacrylate was left behind to bond with the new cement column. Cement fracture, complete demarcation, and young age were negatively correlated with survivorship.

Predisposing factors in fixation failure of femoral prostheses following primary Charnley low friction arthroplasty. A 10- to 20-year followup study.

To identify factors affecting radiologically detected loosening of the Charnley femoral prosthesis, 326 femoral prostheses with 10- to 20-year followup were studied. After observation of postoperative radiological changes, the criteria for fixation failure detected radiologically, of femoral prostheses were defined as progression or accompanying occurrences of subsidence, demarcation, separation of the prosthesis from cement, cement fracture, or endosteal cavitation. Sixteen femoral prostheses (4.9%) developed radiologically detected fixation failure. Male gender, low canal flare index, low femoral score, large medullary canal width, low implant (cement and stem)/canal ratio, low stem/canal ratio, and varus orientation of the stem affected fixation failure. Inadequate cementing techniques such as low implant/canal and stem/canal ratios and varus stem orientation might be within the surgeon's control and should be avoided. An unfavorable canal geometry (stovepipe canal) and osteopenia of the femur, indicated by a low femoral score, are risk factors that might be out of the surgeon's control, and require future research.

Risk factors affecting radiological failure of the socket in primary Charnley low friction arthroplasty. A 10- to 20-year followup study.

To identify the factors affecting Hodgkinson Type 3 or 4 radiological demarcation (presence of complete demarcation or migration, respectively) of the Charnley socket, 328 sockets with 10- to 20-year followup were studied. Fifty-five sockets (16.8%) developed Type 3 or 4 demarcation. In the osteoarthrosis group (237 sockets), removal of eburnated bone at the acetabular roof, the presence of large acetabular angles before and after surgery, and high placement of the socket were related to development of Type 3 or 4 demarcation. In the rheumatoid group (32 sockets), young patient age predisposed the socket to Type 3 or 4 demarcation. Rapid polyethylene wear, correlated with young age, male gender, and thin cement mantle in Zones I and II, was another important factor related to Type 3 or 4 demarcation in both groups and in the entire series. These risk factors should be taken into account when assessing the indications for arthroplasty, when performing arthroplasty, and when educating the patient.

Postoperative sciatic and femoral nerve palsy with reference to leg lengthening and medialization/lateralization of the hip joint following total hip arthroplasty.

The radiographs and prospective records of 1284 (1152 primary and 135 revisions) Charnley low friction arthroplasties performed by one surgeon were studied in reference to postoperative elongation of the limb and lateralization or medialization of the center of rotation of the hip joint and their effect on postoperative nerve palsy. Displacement of the center of the hip joint in relation to fixed points on the pelvis was measured. In primary low friction arthroplasties, leg lengthening ranged from 0.4 to 4 cm; in the revision group, they ranged from 0.04 to 5.8 cm. Sixty-six hips were lengthened more than 2 cm. The center of rotation of the hip was lateralized in 18.1% of cases and medialized in 61.9%. A single case of postoperative sciatic nerve palsy (the result of laceration of the sciatic nerve at surgery) was identified. These study results indicate that nerve injuries after total hip arthroplasty may be caused by local insult, and may not be related to elongation of the limb or postoperative alteration of the center of rotation of the hip.

Design optimization of a prosthesis stem reinforcing shell in total hip arthroplasty.

The use of a perforated, titanium funicular shell to support the proximal femoral cortex in total hip arthroplasty was evaluated with the aid of both analytical and numerical techniques. The principal interactions between the femoral cortex, the metal shell, the implant stem and the acrylic bone cement were modeled using beam on elastic foundations theory and two-dimensional elasticity theory. Subsequent formulation of this model as a nonlinear design optimization problem enabled the determination of the dimensions of the implant and reinforcing shell which minimized an objective function based on a simplified material failure criterion. Two cases were examined, each with two cervico-diaphyseal angles: case A: with a rigid contact between a proximal prosthesis collar and the calcar femorale and case B: no collar contact (a collarless prosthesis or post-operative loosening). Case A achieved an optimal solution at a stem diameter 11-23 percent of the cortex inner diameter, a stem length to diameter ratio of 12-40, shell diameter 22-53 percent and thickness 0.2-7.2 percent of the cortex inner diameter and thickness, respectively. Case B achieved an optimal solution at a stem diameter 67-92 percent of the cortex inner diameter, length to diameter ratio of 4-6, and no shell. In case A the collar support makes the type of internal fixation unimportant, while in the more realistic case B, the shell is not recommended.

Intrapelvic migration of total hip prostheses. Operative treatment.

We describe a safe operative approach for removal of a prosthesis that has migrated into the pelvis, and we recommend that a two-stage reconstruction be done when revising the total hip-replacement arthroplasty. The first stage consists of the removal of the femoral component and cement through a lateral transtrochanteric approach, followed by removal of the acetabular component through an abdominal-retroperitoneal approach to permit exposure of the major intrapelvic structures and to ascertain their relationship to the acetabular component and cement. After the acetabular component has been removed, bone grafts are applied to the pelvis. Postoperatively, the patient is placed in traction for a time and then is allowed to walk with non-weight-bearing. The second stage of reconstruction, consisting of hip replacement, is performed nine to twelve months after the first stage. A satisfactory result was obtained in the four patients for whom we followed this operative regimen. In one patient, the first-stage procedure yielded a satisfactory result and the second stage was not done.

Incidence and mechanism of failure of cemented acetabular component in total hip arthroplasty.

Clinical results today seem to suggest that acrylic cement is crucial in producing immediate and reproducible results of pain-free joints following total hip replacement. Proper application by the use of contemporary techniques may be suitable in most conditions requiring hip replacement. The incidence of acetabular failure in a specific group of patients at risk may warrant experimentation by the use of a noncemented system. The mechanism of failure of low-friction arthroplasty may be multifaceted, but our experience indicates that the mechanisms of failure of the acetabulum have been due to excessive deepening and expansion of the acetabulum, once thought to be fundamental to the procedure. A rudimentary technique of cement pressurization, both in the femur and in the acetabulum, also may have played a part in late failures of this procedure. Early demarcation at the cement-bone interface was prevalent in young and active or heavy individuals. Demarcation and loosening were time-dependent phenomena. Demarcation and loosening also appeared with the aging process and increased osteopenia. A higher incidence of loosening also was observed in young and light-weight individuals, with presumably increased elasticity of the pelvic bone.