Evidence of a hydraulically challenging reach serving as a barrier for the upstream migration of infection-burdened adult steelhead.

Anadromous fishes such as steelhead trout, Oncorhynchus mykiss, are exposed to a suite of infectious agents and migratory challenges during their freshwater migrations. We assessed infectious agent load and richness and immune system gene expression in gill tissue of Bulkley River (British Columbia, CA) steelhead captured at and upstream of a migratory barrier to evaluate whether infectious burdens impacted migration success. We further considered the potential influences of water temperature, sex and fish size on host infectious agents and transcription profiles. There were eight infectious agents detected in steelhead gill tissue, with high prevalence of the bacteria Candidatus Branchiomonas cysticola (80%) and Flavobacterium psychrophilum (95%) and the microparasite Sphaerothecum destruens (53%). Fish sampled at the falls had significantly greater relative loads of Ca. B. cysticola and F. psychrophilum, higher infectious agent richness and differential gene expression compared to fish captured upstream. Flavobacterium psychrophilum was only associated with immune gene expression (particularly humoral immunity) of fish sampled at the falls, while water temperature was positively correlated with genes involved in the complement system, metabolic stress and oxidative stress for fish captured upstream. This work highlights interesting differences in agent-host interactions across fisheries and suggests that hydraulic barriers may reduce the passage of fish with the heaviest infectious agent burdens, emphasizing the selective role of areas of difficult passage. Further, this work expands our knowledge of infectious agent prevalence in wild salmonids and provides insight into the relationships between infectious agents and host physiology.

Are low sun exposure and/or vitamin D risk factors for type 1 diabetes?

The global variation in type 1 diabetes (T1D) incidence rates is one of the most significant observed for any non-communicable disease. Geographical patterns in incidence suggest that low sun exposure may contribute to the wide disparity, with incidence rates generally increasing with distance from the Equator. T1D development is associated with hyperactivity of the adaptive immune system leading to autoimmune destruction of insulin-secreting pancreatic ß cells. Both exposure to ultraviolet radiation (UVR) and vitamin D, with their known immunosuppressive effects, have the potential to delay or inhibit the disease. Efforts to confirm the role of UVR by vitamin D dependent and independent pathways in the pathogenesis of T1D have been challenged by inconsistent results among studies. Human observational studies and animal and in vitro experiments indicate that at least some of the benefits of sun exposure come from improved vitamin D status. There is no evidence of benefit for T1D risk of vitamin D supplementation during pregnancy at current recommended levels (400 IU per day); but some evidence supports that higher sun exposure and/or vitamin D sufficiency in pregnancy, or supplementation in early life, decreases T1D risk. Further research is required to confirm an association between UVR exposure and T1D and clarify the mechanisms involved.

Observational study of subclinical diabetic macular edema.

PURPOSE: To determine the rate of progression of eyes with subclinical diabetic macular edema (DME) to clinically apparent DME or DME necessitating treatment during a 2-year period. METHODS: In all, 43 eyes from 39 study participants with subclinical DME, defined as absence of foveal center edema as determined with slit lamp biomicroscopy but a center point thickness (CPT) between 225 and 299 µm on time domain (Stratus, Carl Zeiss Meditec) optical coherence tomography (OCT) scan, were enrolled from 891 eyes of 582 subjects screened. Eyes were evaluated annually for up to 2 years for the primary outcome, which was an increase in OCT CPT of at least 50 µm from baseline and a CPT of at least 300 µm, or treatment for DME (performed at the discretion of the investigator). RESULTS: The cumulative probability of meeting an increase in OCT CPT of at least 50 µm from baseline and a CPT of at least 300 µm, or treatment for DME was 27% (95% confidence interval (CI): 14%, 38%) by 1 year and 38% (95% CI: 23%, 50%) by 2 years. CONCLUSIONS: Although subclinical DME may be uncommon, this study suggests that between approximately one-quarter and one-half of eyes with subclinical DME will progress to more definite thickening or be judged to need treatment for DME within 2 years after its identification.

Temporal changes in blood variables during final maturation and senescence in male sockeye salmon Oncorhynchus nerka: reduced osmoregulatory ability can predict mortality.

This study is the first to characterize temporal changes in blood chemistry of individuals from one population of male sockeye salmon Oncorhynchus nerka during the final 6 weeks of sexual maturation and senescence in the freshwater stage of their spawning migration. Fish that died before the start of their historic mean spawning period (c. 5 November) were characterized by a 20-40% decrease in plasma osmolality, chloride and sodium, probably representing a complete loss of osmoregulatory ability. As fish became moribund, they were further characterized by elevated levels of plasma cortisol, lactate and potassium. Regressions between time to death and plasma chloride (8 October: P < 0·001; 15 October: P < 0·001) indicate that plasma chloride was a strong predictor of longevity in O. nerka. That major plasma ion levels started to decline 2-10 days (mean of 6 days) before fish became moribund, and before other stress, metabolic or reproductive hormone variables started to change, suggests that a dysfunctional osmoregulatory system may initiate rapid senescence and influence other physiological changes (i.e. elevated stress and collapsed reproductive hormones) which occur as O. nerka die on spawning grounds.

Clinical trial: 2-L polyethylene glycol-based lavage solutions for colonoscopy preparation - a randomized, single-blind study of two formulations.

BACKGROUND: The 2-L polyethylene glycol (PEG) lavage solutions provide efficacy similar to that of standard 4-L PEG formulations in spite of the reduced volume. The comparative efficacy and tolerability of two formulations of 2-L PEG solution remain unknown. AIMS: To assess the efficacy, safety and tolerability of PEG + Bis compared with PEG + Asc, and to study the effect of bowel cleansing quality on adenoma detection rates. METHODS: Patients were randomized to receive either 2-L PEG with ascorbic acid (PEG + Asc) or 2-L PEG plus bisacodyl 10 mg (PEG + Bis). The primary endpoint was overall colon cleansing score, assessed by blinded investigators using a validated four-point scale. Secondary endpoints included adenoma detection rate, patient tolerability and compliance and adverse events. RESULTS: Fifty-two patients received PEG + Asc and 55 patients received PEG + Bis. Overall colon cleansing scores (+/-s.d.) were 1.40 +/- 0.69 and 1.75 +/- 0.70 (P < 0.003) in the PEG + Asc and PEG + Bis groups, respectively. Excellent and good ratings were recorded in 69% and 23% receiving PEG + Asc compared to 38% and 51% (P = 0.01) of patients receiving PEG + Bis. More adenomas were detected in colonoscopies performed with PEG + Asc (39%) than in those performed with PEG + Bis (20%) (P = 0.04). Patient tolerability and safety were similar with both preparations. CONCLUSION: The use of PEG + Asc resulted in better colon cleansing and higher adenoma detection rates compared with PEG + Bis.

Ophthalmology inpatient consultation.

OBJECTIVE: To profile inpatients and eye problems evaluated and managed by the Ophthalmology Consultation Service of a large university teaching hospital. DESIGN: A hospital-based retrospective, cross-sectional study. PARTICIPANTS: One thousand four hundred seventy-two patients admitted to the University of California Los Angeles Medical Center. METHODS: We reviewed the inpatient medical records, discharge summaries, and Ophthalmology Consultation Service notes of every patient evaluated by the Service from July 1990 through January 1997. MAIN OUTCOME MEASURES: We recorded demographic information, hospitalization information, and eye examination information, including reason for consultation, type of consultation (screening examination, new eye problem, or preexisting eye problem), as well as primary and secondary ophthalmologic diagnoses. RESULTS: Internal medicine services requested 39.7% of consultations, surgery services 20.9%, and trauma services 13.5%. There were 92 different reasons why consultations were requested. The most common reason was decreased vision. Eye problems that developed either on the day of admission or some time during hospitalization accounted for 39.6% of consultations, preexisting eye problems accounted for 31.6%, and screening examinations for the remaining 28.7%. We recorded 166 unique primary ophthalmologic diagnoses and 130 unique secondary ophthalmologic diagnoses. The top five common primary ophthalmologic diagnoses were refractive error (88 patients), fungal endophthalmitis ruled out (80 patients), conjunctivitis (56 patients), diabetic retinopathy (52 patients), and corneal abrasion (52 patients). Refractive error was the most common secondary ophthalmologic diagnosis (201 patients). Inpatient diagnostic or surgical procedures were performed 7911 times. There were 947 unique primary and 1391 unique secondary hospital discharge diagnoses. The most common primary discharge diagnosis, human immunodeficiency virus infection, accounted for only 1.6% of all hospitalizations, indicating a considerable diversity of systemic disease in the study population. CONCLUSIONS: This study profiled the typical patients and eye problems an ophthalmologist may expect to encounter when inpatient consultation is requested. The information may be useful for the planning and management of consultation services in residency training programs.

Cataract surgery after retinal surgery.

Many patients require surgery for cataract after retinal surgery. When evaluating patients preoperatively, the surgeon should pay careful attention to the assessment of visual function and potential acuity, and to the slit lamp examination of the lens, posterior capsule, anterior cortical vitreous, and zonules. The surgeon's technique must account for increased nuclear sclerosis, intraoperative miosis, a characteristically longer axial length, and fluctuations in anterior chamber depth from movement of the iris-lens diaphragm. Posterior capsule plaques are not unusual. Posterior capsule opacification is the most frequent late complication. Visual outcomes are usually good except when limited by pre-existing macular pathology. Vision-threatening complications of cataract surgery are unusual.

Suppression of apoptosis induced by growth factor withdrawal by an oncogenic form of c-Cbl.

The v-Cbl oncogene induces myeloid and B-cell leukemia; however, the mechanism by which transformation occurs is not understood. An oncogenic form of c-Cbl (Cbl-DeltaY371) was expressed in the interleukin-3 (IL-3)-dependent cell line 32Dcl3 to determine whether it was able to induce growth factor-independent proliferation. We were unable to isolate clones of transfected 32Dcl3 cells expressing Cbl-DeltaY371 that proliferated in the absence of IL-3. In contrast, 32Dcl3/Cbl-DeltaY371 cells did not undergo apoptosis like parental 32Dcl3 cells when cultured in the absence of IL-3. Both 32Dcl3 and 32D/CblDeltaY371 cells arrested in G(1) when cultured in the absence of IL-3. Approximately 18% of the 32Dcl3 cells cultured in the absence of IL-3 for 24 h were present in a sub-G(1) fraction, while only 4% of the 32D/Cbl-DeltaY371 and 2% of the 32D/Bcl-2 cells were found in a sub-G(1) fraction. There was no difference in the pattern of tyrosine-phosphorylated proteins observed following stimulation of either cell type with IL-3. The phosphorylation of JAK2, STAT5, and endogenous c-Cbl was identical in both cell types. No differences were detected in the activation of Akt, ERK1, or ERK2 in unstimulated or IL-3-stimulated 32D/Cbl-DeltaY371 cells compared with parental 32Dcl3 cells. Likewise, there was no difference in the pattern of phosphorylation of JAK2, STAT5, ERK1, ERK2, or Akt when 32Dcl3 and 32D/CblDY371 cells were withdrawn from medium containing IL-3. The protein levels of various Bcl-2 family members were examined in cells grown in the absence or presence of IL-3. We observed a consistent increased amount of Bcl-2 protein in five different clones of 32D/Cbl-DeltaY317 cells. These data suggest that the Cbl-DeltaY371 mutant may suppress apoptosis by a mechanism that involves the overexpression of Bcl-2. Consistent with this result, activation of caspase-3 was suppressed in 32D/Cbl-DeltaY371 cells cultured in the absence of IL-3 compared with 32Dcl3 cells cultured under the same conditions.

Outcomes of cataract surgery in monocular patients.

PURPOSE: To determine the best corrected visual acuity (BCVA) outcomes and surgical complications in a consecutive series of functionally monocular patients who had phacoemulsification and intraocular lens (IOL) implantation. SETTING: University-based referral practice, Los Angeles, California, USA. METHODS: The medical records of 93 monocular patients who had phacoemulsification and IOL implantation between December 1991 and February 1999 were reviewed. Patients were considered to be monocular if Snellen BCVA in their fellow eye (the eye not having surgery) was worse than 20/200. Recorded were demographic information, anesthesia method, additional surgery, IOL model, preoperative and postoperative BCVA, reason for poor vision in the unoperated eye, co-morbidities in the operated eye, intraoperative and postoperative complications, length of follow-up, and postoperative procedures. RESULTS: Mean patient age was 72 years and mean follow-up, 6 months. Thirteen patients (14%) were monocular from complications of surgery. Eighty patients (86%) were monocular because of medical eye conditions. Ocular co-morbidities were present in 75% of eyes having surgery. Preoperative median BCVA was 20/60. Median BCVA was 20/30 by the final scheduled follow-up examination and 20/25 by the final follow-up examination. Thirty-seven percent of eyes were correctable to 20/20 or better, and 67% were correctable to 20/40 or better. Two eyes lost BCVA by the final scheduled postoperative examination, and 3 eyes lost BCVA by the final follow-up examination. Final BCVA of worse than 20/40 was always related to preexisting macular or optic-nerve pathology. There were 16 intraoperative or early postoperative complications. The most common (3 eyes) was posterior capsule plaque that could not be removed by capsule polishing. Twenty eyes (22%) had subsequent surgical procedures, the most common being laser posterior capsulotomy. No patient who was monocular from surgical complications had similar problems with second-eye cataract surgery. CONCLUSIONS: Best corrected visual acuity, the standard measure of efficacy in cataract surgery, improved a median of 3 to 4 Snellen lines. The safety of the procedure, as evidenced by the small number of patients who lost BCVA or experienced surgical complications, was satisfactory. Functionally monocular patients are likely to have ocular co-morbidities, some of which may limit the final visual outcome of surgery.

Visual complaints associated with the AcrySof acrylic intraocular lens(1).

PURPOSE: To describe the visual complaints of a series of patients implanted with the AcrySof(R) (Alcon Surgical) acrylic intraocular lens (IOL) that resolved with IOL exchange. SETTING: Jules Stein Eye Institute, Los Angeles, California, and John A. Moran Eye Center, Salt Lake City, Utah, USA. METHODS: This was a retrospective review of patients who had AcrySof IOL exchange from January 1997 to December 1998. RESULTS: Eight patients (9 eyes) with bothersome visual symptoms following AcrySof IOL implantation were identified. Problems included glare, halos around point light sources, and peripheral arcs of light, often worse at night. In each case, the IOL was well-centered in the capsular bag and there was no significant posterior capsule opacification. Six patients (7 eyes) had the MA30BA model with a 5.5 mm optic, and 2 patients (2 eyes) had the MA60BM model with a 6.0 mm optic. No extralenticular reasons for the patients' complaints could be identified. Exchanging the AcrySof IOLs with silicone or poly(methyl methacrylate) IOLs alleviated most symptoms. In 5 of 8 patients, dysphotopsias resolved completely. CONCLUSIONS: A small number of patients implanted with AcrySof IOLs have specific complaints of glare, halos, and peripheral arcs of light. Optical considerations that may help explain these symptoms include the high refractive index of the IOL material and the truncated design of the optic. Patients who are highly observant and those with large pupils may be particularly symptomatic. Intraocular lens exchange may be necessary in some cases.

Posterior dislocation of a plate-haptic silicone intraocular lens with large fixation holes.

We present a patient who had uneventful phacoemulsification with in-the- bag implantation of a silicone plate-haptic posterior chamber intraocula r lens (IOL) with 1.15 mm fixation holes. Six months after a neodymium: YAG laser capsulotomy, the IOL spontaneously dislocated posteriorly. A pars plana vitrectomy was performed, the IOL was explanted, and a 3-piece loop-haptic IOL was implanted in the ciliary sulcus. Eight weeks after surgery, best corrected visual acuity was 20/20.

Digital overlay technique for documenting toric intraocular lens axis orientation.

PURPOSE: To describe a digital overlay technique for documenting toric intraocular lens (IOL) axis alignment. SETTING: Jules Stein Eye Institute and the Department of Ophthalmology, University of California at Los Angeles School of Medicine, Los Angeles, California, USA. METHODS: Digital overlay imaging was used to evaluate the alignment of Staar toric IOLs in 4 eyes of 3 patients who had regular corneal astigmatism at the time of cataract surgery. Lens axes were determined by computerized analysis of digitally scanned retroillumination photographs. A stock digital image of a Staar AA4203TF toric IOL was superimposed on corneal topography images to document IOL alignment with the steep corneal meridian. RESULTS: Digital overlay images demonstrated that 3 IOLs in the sample group were within 5 degrees and 1 was within 20 degrees of the intended axis at the time of the final postoperative examination. Slitlamp lens axis estimations were 3 to 18 degrees different from that determined by this technique. CONCLUSION: Digital overlay imaging of correctly oriented toric IOLs on computerized corneal topography maps represents an intuitive, accurate, and visually appealing method of documenting toric IOL axis alignment.

Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during bacterial meningitis: association with blood-brain barrier damage and neurological sequelae.

To evaluate the spectrum and regulation of matrix metalloproteinases (MMPs) in bacterial meningitis (BM), concentrations of MMP-2, MMP-3, MMP-8, and MMP-9 and endogenous inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were measured in the cerebrospinal fluid (CSF) of 27 children with BM. MMP-8 and MMP-9 were detected in 91% and 97%, respectively, of CSF specimens from patients but were not detected in control patients. CSF levels of MMP-9 were higher (P<.05) in 5 patients who developed hearing impairment or secondary epilepsy than in those who recovered without neurological deficits. Levels of MMP-9 correlated with concentrations of TIMP-1 (P<.001) and tumor necrosis factor-alpha (P=.03). Repeated lumbar punctures showed that levels of MMP-8 and MMP-9 were regulated independently and did not correlate with the CSF cell count. Therefore, MMPs may derive not only from granulocytes infiltrating the CSF space but also from parenchymal cells of the meninges and brain. High concentrations of MMP-9 are a risk factor for the development of postmeningitidal neurological sequelae.

Approach to colon polyps in the elderly.

Colorectal cancer is a common but potentially preventable disease. Nearly all colorectal cancers are thought to arise from adenomatous polyps. The conclusions from the National Polyp Study strongly support the concept that the removal of polyps may prevent the future development of colorectal cancer. With the growing acceptance of screening for colorectal cancer, many elderly patients with adenomatous polyps will be discovered. Because increasing age is a powerful determinant of a higher prevalence of colonic neoplasia in asymptomatic individuals, physicians will need to be prepared to make informed decisions regarding the treatment of elderly patients with colonic polyps. The literature is reviewed and guidelines are formed regarding the optimal surveillance interval for patients with colonic polyps. The age at which surveillance and screening for colorectal neoplasia should stop is also reviewed. Conclusions are based on the currently available data.

Increased expression of osteonectin/SPARC mRNA and protein in age-related human cataracts and spatial expression in the normal human lens.

PURPOSE: We have previously reported increased levels of Osteonectin/SPARC transcript in age-related cataractous compared to normal human lenses. The purpose of the present study was to evaluate the corresponding levels of osteonectin/SPARC protein in age-related cataractous relative to normal lenses and to evaluate the levels of osteonectin/SPARC transcript in specific types of age-related human cataracts. The spatial expression of osteonectin/SPARC was also evaluated in normal human lenses. METHODS: Specific types of age-related cataracts were collected and graded. Normal human lenses were microdissected into epithelia and fibers. Osteonectin/SPARC protein levels were monitored by Western immunoblotting, and transcript levels were evaluated by reverse transcriptase polymerase chain reaction (RT-PCR). Osteonectin/SPARC expression patterns were examined by RT-PCR and by immunostaining. RESULTS: Higher levels of osteonectin/SPARC protein were detected in age-related cataractous relative to normal human lenses. Increased levels of osteonectin/SPARC transcript were also detected in posterior-subcapsular and nuclear cataractous lenses relative to normal lenses. Osteonectin/SPARC transcripts were detected in the lens epithelium but not fibers. Osteonectin/SPARC protein levels were highest in the peripheral lens epithelium. CONCLUSIONS: Consistent with our previous studies on osteonectin/SPARC mRNA levels, osteonectin/SPARC protein levels were also elevated in cataractous compared to normal human lenses. Increased levels of osteonectin/SPARC mRNA were also found in nuclear and posterior-subcapsular cataracts relative to normal lenses. Osteonectin/SPARC expression is confined to the lens epithelium, and osteonectin/SPARC levels are highest in the peripheral lens epithelium.

Phacoemulsification and lens implantation after scleral buckling surgery.

PURPOSE: To determine the intraoperative and postoperative complications and best-corrected visual acuity outcomes of eyes undergoing phacoemulsification and intraocular lens implantation after retinal detachment repair by the scleral buckling technique. METHODS: The charts of all patients who underwent phacoemulsification and intraocular lens implantation between July 1991 and May 1998 in two surgical practices were reviewed to identify eyes with a history of retinal detachment repaired by the scleral buckling technique. Eyes with a history of pars plana vitrectomy were excluded. Demographic and surgical data, preoperative and postoperative best-corrected visual acuity, and intraoperative and postoperative complications were recorded. RESULTS: We identified 34 eyes of 32 patients. The mean interval from retinal detachment repair to phacoemulsification was 12.4 years. The mean interval from phacoemulsification to final examination was 20 months. Risk factors for retinal detachment included isolated myopia (82%), myopia with lattice retinal degeneration (5.9%), and myopia with trauma (8.8%). One eye (2.9%) had no identifiable risk factors. Final best-corrected visual acuity of 20/40 or better was attained in 29 (85%) of 34 eyes and 20/20 or better in 18 (53%) of the eyes. Of the five eyes with the lowest best-corrected visual acuity, three had a macula-off retinal detachment; one had a posterior capsule opacity, epiretinal membrane, and corneal edema secondary to ocular ischemia; and one had advanced glaucoma. All five eyes still experienced an improvement in best-corrected visual acuity. With regard to complications, one eye had a posterior capsular tear with vitreous loss and another developed a postoperative retinal tear. Posterior capsule opacification requiring laser capsulotomy developed in 13 eyes (38%). No eye developed a retinal redetachment. CONCLUSION: Phacoemulsification and intraocular lens implantation can be performed safely after scleral buckling surgery and excellent best-corrected visual acuity results can be attained in most eyes. No modification of surgical technique is necessary. No retinal redetachment occurred in this series.

Randomized clinical comparison of Healon GV and Viscoat.

PURPOSE: To compare the ability of Healon GV (sodium hyaluronate 1.4%) and Viscoat (sodium chondroitin sulfate 4.0%-sodium hyaluronate 3.0%) to protect the corneal endothelium during endocapsular phacoemulsification and foldable intraocular lens (IOL) implantation. SETTING: A small ophthalmology group practice. METHODS: One hundred forty patients were randomized, 70 per group, in a prospective, partially masked study of cataract surgery using Healon GV or Viscoat. One ophthalmologist performed all surgery. Primary outcome variables were the 2 week postoperative changes in corneal thickness, endothelial cell density, mean endothelial cell size, and endothelial cell hexagonality. Several secondary variables were measured, and an analysis of the statistical power of the study was performed. RESULTS: There were no statistically significant differences between groups in terms of age (P = .856), cataract density (P = .117), preoperative best corrected visual acuity (BCVA) (P = .892), postoperative BCVA (P = .969), amount of viscoelastic material used during surgery (P = .444), amount of irrigating solution used (P = .125), or phacoemulsification time (P = .088). It took longer to remove the Viscoat than the Healon GV (P < .001), and total operating time for the Viscoat group was longer (P < .001). Two weeks after surgery, there were no significant differences between groups in corneal thickness (P = .362), endothelial cell density (P = .351), or mean endothelial cell size (P = .610). However, Viscoat preserved the hexagonal shape of endothelial cells slightly better than Healon GV (P = .043). The study had sufficient power to detect clinically significant differences in corneal thickness, endothelial cell density, and endothelial cell size. CONCLUSIONS: Healon GV and Viscoat were comparable in their ability to protect the corneal endothelium during endocapsular phacoemulsification and foldable IOL implantation. Results may vary, however, if phacoemulsification is performed anterior to the iris plane.

Matrix metalloproteinase upregulation in chronic inflammatory demyelinating polyneuropathy and nonsystemic vasculitic neuropathy.

OBJECTIVE: To determine the expression pattern and cellular source of matrix metalloproteinases (MMPs) in chronic inflammatory demyelinating polyneuropathy (CIDP) and nonsystemic vasculitic neuropathy (NSVN). BACKGROUND: MMPs are endopeptidases involved in tissue destruction and infiltration by immune cells in multiple sclerosis and Guillain-Barré syndrome. Enzyme inhibitors of MMPs attenuate clinical symptoms in corresponding animal models of these diseases. MMP inhibition may therefore be a novel approach for the treatment of CIDP and NSVN. However, the spectrum of MMPs expressed in chronic inflammatory neuropathies has not been established. METHODS: The expression of MMP-2, MMP-3, MMP-7, and MMP-9 in T cells, macrophages, and stromal cells in CIDP, NSVN, and noninflammatory neuropathies (NIN) was quantitated by immunohistochemistry. Results were correlated with clinical and electrophysiologic findings. RESULTS: The production of MMP-2 and MMP-9 is increased in nerve tissue in CIDP and NSVN compared with NIN. T cells are the predominant source of MMP-2 and MMP-9 in CIDP and NSVN, whereas macrophages contribute only to a minor extent. Stromal cells of the perineurium/epineurium are an additional source of MMP-2 in NSVN, but not in CIDP. Expression of MMP-3 and MMP-7 was not detectable in CIDP or NSVN. Expression of MMP-2 and MMP-9 did not correlate with clinical disease activity and electrophysiologic measurements. CONCLUSIONS: The upregulation of MMP-2 and MMP-9 is a specific feature of CIDP and NSVN, and selective inhibitors of these enzymes could be used to prevent inflammatory tissue damage. The similar increase of MMP-2 and MMP-9 in both demyelinating (CIDP) and nondemyelinating (NSVN) neuropathies raises doubts about whether MMPs play a primary role in demyelination.

A central role for astrocytes in the inflammatory response to beta-amyloid; chemokines, cytokines and reactive oxygen species are produced.

Alzheimer's disease (AD) is the commonest form of adult onset dementia and is characterised neuropathologically by the accumulation of plaques containing beta-amyloid (A beta) fibrils, reactive astrocytes, activated microglia, and leukocytes. A beta plays a role in the pathology of AD by directly causing neuronal cytotoxicity and stimulating microglia to secrete cytokines and reactive oxygen species (ROS) which also damage neurons. Here, we demonstrate that A beta activates astrocytes and oligodendrocytes (the most common cell types in the brain) to produce chemokines, in particular MCP-1 and RANTES, which serve as potent in vitro microglial and macrophage chemoattractants. Furthermore, we have shown that A beta activates astrocytes to upregulate pro-inflammatory cytokine expression and enhances the production of ROS. We propose therefore that A beta-mediated astrocyte activation initiates an inflammatory cascade which could be targeted for therapeutic intervention in AD.