The infrapatellar fat pad in knee osteoarthritis: An important source of interleukin‐6 and its soluble receptor

Objective

Obesity is a potent risk factor in knee osteoarthritis (OA). It has been suggested that adipokines, secreted by adipose tissue (AT) and largely found in the synovial fluid of OA patients, derive in part from the infrapatellar fat pad (IFP), also known as Hoffa's fat pad. The goal of this study was to characterize IFP tissue in obese OA patients and to compare its features with thigh subcutaneous AT to determine whether the IFP contributes to local inflammation in knee OA via production of specific cytokines.

Methods

IFP and subcutaneous AT samples were obtained from 11 obese women (body mass index ≥30 kg/m²) with knee femorotibial OA. Gene expression was measured by real‐time quantitative polymerase chain reaction. Cytokine concentrations in plasma and in conditioned media of cultured AT explants were determined by enzyme‐linked immunosorbent assay or by Luminex xMAP technology.

Results

In IFP tissue versus subcutaneous AT, there was a decrease in the expression of genes for key enzymes implicated in adipocyte lipid metabolism, whereas the expression levels of genes for AT markers remained similar. A 2‐fold increase in the expression of the gene for interleukin‐6 (IL‐6), a 2‐fold increase in the release of IL‐6, and a 3.6‐fold increase in the release of soluble IL‐6 receptor (sIL‐6R) were observed in IFP samples, compared with subcutaneous AT, but the rates of secretion of other cytokines in IFP samples were similar to the rates in subcutaneous AT. In addition, leptin secretion was decreased by 40%, whereas adiponectin secretion was increased by 70%, in IFP samples versus subcutaneous AT.

Conclusion

Our results indicate that the IFP cytokine profile typically found in OA patients could play a role in paracrine inflammation via the local production of IL‐6/sIL‐6R and that such a profile might contribute to damage in adjacent cartilage.

     

Fos protein induction,neuropathology, and pharmacological protection after excitotoxic brain insult

The excitotoxins kainic acid and N-methyl d-aspartate (NMDA) were unilaterally injected in the rat striatum. Kainic acid injections resulted in a widespread pattern of Fos protein induction, mainly involving cortical olfactory structures and hippocampus. Immunoreactive cells were observed in large number 2–24 h after injection and had almost completely disappeared by 48 h. NMDA injections elicited a shorter (2–8 h) expression of Fos protein, involving a lower number of cells in cortical olfactory structures, a much larger number of cells in the other cortical regions, and not involving the hippocampus at all. Characteristically none of the two excitotoxins stimulated Fos expression from striatal neurons, even in the close vicinity of the needle tract. In addition to striatal lesions almost equivalent in size, the two excitotoxins caused distant lesions of different extension: kainic acid resulted in extensive neuronal degeneration in the olfactory-entorhinal cortices and among pyramidal neurons of the hippocampus; NMDA caused a less widespread neurodegeneration, restricted to the olfactory cortex. Administration of the competitive NMDA antagonist CGP 39551 largely prevented the distant, but not the local, neuropathological changes caused by intrastriatal kainic acid or NMDA. The expression of Fos protein, however, was partially prevented only in NMDA cases. The present results show a good relationship between the spreading of circuit overexcitation caused by the two excitotoxins and the regional and temporal patterns of Fos expression. The relationship between Fos expression and neuropathological condition remains, however, elusive.     

Effect of β-endorphin on cell growth and cell death in human peripheral blood lymphocytes

Beta-endorphin (β-end) was investigated for its ability to influence sequential metabolic events that accompany the movements of T-lymphocytes into the cell cycle. When cultured lymphocytes are exposed to this endogenous opioid peptide an increase in polyamine transport across cell membrane is observed. This membrane modification is an early cell cycle event, whose enhancement leads to the intracellular polyamine accumulation. It is shown that β-end is able to enhance spermidine transport and that the exposition of cells to this peptide is perceived as an apoptotic signal. The possible relationship between induction of apoptotic death and enhancement of polyamine uptake is discussed.     

Incidence of epilepsy in extremely low-birthweight infants (<1,000 g): A population study of central and southern Sardinia

Purpose:   With the development of intensive care, the survival of extremely low-birthweight (ELBW) infants (<1,000 g) has greatly improved. The aim of our study was to report the incidence of epilepsy after a follow-up of >7 years in a population of ELBW children, born in central and southern Sardinia between 1991 and 2000.
Methods:   We analyzed data of 104 children. All infants had had serial cranial ultrasound echography (CUE) in the neonatal period and some also had magnetic resonance imaging (MRI). At last follow-up we evaluated the occurrence of epilepsy through a review of clinical charts and a structured telephone interview.
Results:   In 11 (10.6%) of 104 of children we observed febrile seizures (FS). Epilepsy occurred in 9 (8.6%) of 104 ELBW children, and in these patients a frequent positive family history for epilepsy and/or FS was present. In four epilepsy patients CUE was highly pathologic, showing intraventricular hemorrhage (IVH) of grade IV and in two mildly abnormal (IVH of grade I–II). In three additional children with normal neonatal ultrasound scan, a later magnetic resonance imaging (MRI) study revealed lesions related to neonatal insult.
Discussion:   In our ELBW population, epilepsy had an incidence clearly superior to that expected in infancy (8.6% vs. 0.6–0.8% ) . A frequent positive familiar history for epilepsy and/or FS suggests that a genetic predisposition may also play a role. Subjects with highly abnormal CUE are a subgroup with high risk for seizures; however, epilepsy can occur even with normal CUE.     

Linkage mapping of a nonspecific form of X‐linked mental retardation (MRX53) in a large Pakistani family

Nonspecific X‐linked mental retardation is a nonprogressive, genetically heterogeneous condition that affects cognitive function in the absence of other distinctive clinical manifestations. We report here linkage data on a large Pakistani family affected by a form of X‐linked nonspecific mental retardation. X chromosome genotyping of family members and linkage analysis allowed the identification of a new disease locus, MRX53. The defined critical region spans approximately 15 cM between DXS1210 and DXS1047 in Xq22.2–26. A LOD score value of 3.34 at no recombination was obtained with markers DXS1072 and DXS8081. © 2001 Wiley‐Liss, Inc.     

Factors influencing outcome of lamivudine in anti-HBe-positive chronic hepatitis B

BACKGROUND/AIMS: Lamivudine has been shown to benefit patients with anti-HBe/HBV-DNA-positive chronic hepatitis B. The aim of the study was to evaluate factors influencing outcome of lamivudine therapy during two years of post-treatment follow-up in a prospective clinical trial. METHODOLOGY: Thirty-one consecutive patients, submitted to liver biopsy, were treated with lamivudine at 100mg/daily for twelve months and followed-up for twenty-four months. The patients were never treated before with interferon or stopped at least six months before starting lamivudine. ALT was measured monthly and HBV-DNA every three months. RESULTS: At the end of therapy 25 (81%) patients had both biochemical and virological response; 2 (6%) patients showed persistent viremia and 4 (13%) patients developed viral resistance during treatment. Twenty-three (92%) out of 25 responders relapsed during the follow-up; over 50% of all cases relapsed within 6 months. The relapse is related to higher HBV-DNA baseline levels. At relapse, 4/23 (17%) patients had symptomatic acute hepatitis. CONCLUSIONS: Lamivudine is associated with the risk of developing viral mutants and, after therapy discontinuation, to high rate of relapse. In relapsing patients severe acute recurrence of hepatitis B may occur. Decisions about lamivudine monotherapy should take into account the limited long-term efficacy, effects of relapse, costs and predictive factors for response.