The role of osmic acid in the treatment of immune synovitis

Thirty-seven New Zealand rabbits were observed for up to 1 year after their knee joints were instilled with 1 ml of 1% osmic acid. A selective destruction of synovial lining cells occurred with a concurrent synovitis, but lining cell regenerated by the eighth week. Nonprogressive abnormalities were also present in the cartilage. When an immune synovitis was induced in both knees of 16 rabbits, the osmic acid treated joint demonstrated a significantly greater synovitis and progressive aberrations compared to the untreated knee.     

Cyclosporin a and tissue antigen matching in bone transplantation: Fibular allografts studied in the dog

We studied the mechanical, metabolic, and histologic properties of short-term nonvascularized cortical bone grafts in a canine fibular graft model. Sham operated nonvascularized autotransplanted and allotransplanted bones were compared. The allografts were performed between dog leukocyte antigen (DLA) class I and II matched; DLA class I and II mismatched; and cyclosporin A (CsA) treated, DLA class I and II mismatched animals. Cyclosporin was given for 1 month, and all the animals were followed for 3 months after surgery. Mechanical properties were investigated using standard torsional tests, metabolic kinetics were assessed using isotopic prelabeling techniques, and histomorphometric analysis of cross-sectional area properties and sequential fluorochrome labels were performed. Autografts were mechanically stronger and stiffer than all the types of allograft. CsA-treated, DLA-mismatched allografts performed better than matched allografts. These in turn were stronger than non-CsA-treated, mismatched allografts, which underwent nearly complete resorption. These relationships were preserved in the metabolic and histologic analyses. In this short-term animal study, although DLA matching resulted in a slight improvement in graft outcome, mismatched grafts in dogs receiving a short course of cyclosporin A fared even better.     

Correction of Anemia with Erythropoietin in Chronic Kidney Disease (stage 3 or 4): Effects on Cardiac Performance

Background It is not clear whether the correction of anemia with erythropoietin (rhuEpo) in patients with chronic kidney disease (CKD) has any benefit on cardiac function and geometry. Most studies are based on indices of systolic function and left ventricular mass (LVM) and the results are conflicting. Patients and methods We sought to investigate the effect of rhuEpo on LV systolic and diastolic performance using conventional and novel echocardiographic indices. Thirty one patients with CKD (stage 3 or 4) were included. Fifteen patients (group I) treated with rhuEpo targeting at Hb ≥13.0 g/dL, while the remaining (group II) were not treated. Clinical and laboratory parameters were recorded at baseline and 1 year later. Ejection fraction (EF) and LVM were carefully determined. Diastolic function was assessed by mitral inflow indices (E and A wave velocities, Edt deceleration time and E/A) and novel indices of mitral annulus motion using Tissue Doppler Imaging (Em, Am, and E/Em). An index of global cardiac function (Tei) was also calculated. Results At baseline, the 2 groups had comparable clinical and laboratory characteristics. After 1 year, a significant improvement in Hb levels (13.6 ± 1.2 vs 10.3 ± 1.2 g/dL, p < 0.05) as well as in systolic and diastolic function indexes was observed in group I compared to group II patients: EF (70.5 ± 7.6 vs 63.4 ± 9.3%, p < 0.05), LVM (116.5 ± 34.9 vs 155.6 ± 51.6 g/m², p < 0.05), Edt (233.9 ± 98.6 vs 166.9 ± 45.1 ms, p < 0.05), Tei index (0.35 ± 0.12 vs 0.51 ± 0.17, p < 0.01) and E/Em (9.7 ± 2.4 vs 14.8 ± 5.2, p < 0.05), respectively. Blood pressure and heart rate did not show significant changes. Conclusions Correction of anemia with rhuEpo in patients with CKD seems to improve cardiac performance and geometry.     

Hippocampal neurogenesis is not required for behavioral effects of environmental enrichment

Environmental enrichment increases adult hippocampal neurogenesis and alters hippocampal-dependent behavior in rodents. To investigate a causal link between these two observations, we analyzed the effect of enrichment on spatial learning and anxiety-like behavior while blocking adult hippocampal neurogenesis. We report that environmental enrichment alters behavior in mice regardless of their hippocampal neurogenic capability, providing evidence that the newborn cells do not mediate these effects of enrichment.     

Behavior on the water maze platform: relationship to learning and open field exploration in aged and adult rats

In the present study we examined whether age-related deficits in the water maze could be accounted for by changes in the behavior on the platform, and whether platform behavior represents some form of exploration, akin to that seen in the open field. Twenty-seven aged and 8 adult rats (26 and 3 months old Wistar rats, respectively) were tested in an empty open field and spatial object exploration task, followed by 9 days of escape learning in a water maze. The aged as compared to the adults exhibited lower levels of open field activity and were deficient in the object displacement task. Escape deficits in the water maze and reduced activity levels on the platform were also found. In the aged, water maze performance was correlated with behavior on the platform, including quiescence, orienting-like activity and turning behavior, a form of axial rotation. In both age groups, turning behavior was also correlated with exploratory activity in the open field. In conclusion, the results support the hypothesis that age-related impairments in the water maze relate to changes in platform behavior, which, in turn, might reflect exploratory activity.     

Erythrocyte PAF-acetylhydrolase activity in various stages of chronic kidney disease: effect of long-term therapy with erythropoietin

BACKGROUND: Erythrocytes represent an important component of the antioxidant capacity of blood, comprising, in particular, intracellular enzymes, including platelet-activating factor acetylhydrolase (PAF-AH) and glutathione peroxidase (Gpx). We evaluated the erythrocyte PAF-AH and Gpx activities in various stages of chronic kidney disease (CKD), and further investigated whether erythropoietin (EPO) administration in these patients has any influence on the enzyme activities. METHODS: Thirty-six patients (19 men and 17 women) with CKD (stages 1 to 5) participated in the study. Thirteen of them presented with CKD stage 1 to 2 (group I), whereas 23 patients presented with CKD stage 3 to 5 and randomized into two groups (i.e., groups II and III). Patients of group II (N= 11) were administered EPO subcutaneously, 50 units per kg once per week. In group III (N= 12), EPO was initiated only when the hemoglobin (Hb) levels decreased during follow-up to less than 9 g/dL. All patients were seen on an outpatient basis at 2 and 4 months. Fifteen normolipidemic age- and sex-matched healthy volunteers also participated in the study and were used as controls. The PAF-AH and Gpx activities were determined in isolated washed erythrocytes. RESULTS: The erythrocyte-associated PAF-AH and Gpx activities were higher in all CKD patient groups at baseline compared to controls, the groups II and III exhibiting significantly higher enzyme activities compared with group I. In all studied populations, both enzyme activities were negatively correlated with the creatinine clearance values. Importantly, the PAF-AH and Gpx activities were progressively decreased during the follow-up in patients not treated with EPO (group III), a phenomenon not observed in patients receiving EPO (group II), or in patients of group I. This reduction in enzyme activities was positively correlated with the decrease in the creatinine clearance values in patients of group III. CONCLUSION: Significant alterations in the erythrocyte-associated PAF-AH and Gpx activities related to the disease stage are observed in CKD patients. Administration of EPO prevented the reduction in enzyme activities observed during the progression of the renal insufficiency, thus preserving the erythrocyte defense mechanisms against oxidative stress.     

Intratubular germ cell neoplasia in a man with ambiguous genitalia, 45,X/46,XY mosaic karyotype,and Y chromosome microdeletions

We report the case of a 17-yr-old male with ambiguous genitalia, 45,X/46,XY mosaic karyotype, and Y chromosome microdeletions. The patient underwent a testicular biopsy at the age of 6 with normal findings. A second biopsy at the age of 17 established the diagnosis of intratubular germ cell neoplasia (ITGCN), which was treated with bilateral orchidectomy. This case report deals with three important issues regarding ITGCN: First, although a prepubertal biopsy can be performed in order to provide evidence for future fertility, it is very unreliable for making a diagnosis of ITGCN. Second, because ITGCN tends to be a generalized procedure that affects both testes in a uniform pattern, a small number of biopsies, even a single one, could be adequate for diagnostic purposes in the majority of cases. Third, although the population that requires screening for ITGCN remains controversial, the early postpubertal period could be the optimum time for a testicular biopsy.     

Correlation of MDR-1, nm23-H1 and H Sema E gene expression with histopathological findings and clinical outcome in ovarian and breast cancer patients

The development of a molecular screening method for cancer patients is of great importance, since it would contribute to the selection of the most effective chemotherapy regimen for each patient. In the present study we applied such a method, semi-quantative RT-PCR analysis, and we examined the expression of the multidrug resistance gene MDR-1, the metastasis suppressor gene nm23-H1 and the non-MDR drug resistant gene H Sema E in 53 ovarian and breast cancer specimens. Moreover, we have correlated the expression profile of these genes with the histopathological findings and clinical outcome of the examined patients. The majority of specimens were found to be positive for MDR-1 and H Sema E gene expression, while nm23-H1 was detected in less than 50% of the patients. Correlation and statistical analysis of the molecular data with clinicopathological features showed that nm23-H1 could serve as a good prognostic factor for ovarian cancer patients. In breast cancer patients, nm23-H1 expression was associated with a 6.1 higher death risk. Ovarian cancer patients who express nm23-H1, but not MDR-1 and H Sema E, tend to have longer survival than patients with any other gene combination. Finally, breast cancer patients with advanced disease showed a better response when they were negative for all the three genes studied. In conclusion this work proposes that the combined study of the expression of different genes may be a useful approach for evaluating patients' response to therapy.