Plasma C3c in immune-mediated neurological diseases: a preliminary report

Plasma C3c levels were examined in 56 patients with immune (27) and non-immune (29) mediated neurological diseases by crossed immunoelectrophoresis. Plasma samples were collected during the active phase of illness in both groups, usually within 7 days of admission. 11 patients (4 Guillain-Barré Syndrome-GBS, 3 chronic inflammatory demyelinating polyneuropathy-CIDP, 4 myasthenia gravis-MG) had their plasma saved sequentially during the active and the recovery phase. Plasma C3c levels were elevated in the group with immune mediated diseases when compared with those of non-immune mediated diseases. The sensitivity and specificity of C3c as a diagnostic test for immune mediated neurological diseases were 61.4 and 100% respectively with a positive and negative predictive value of 100 and 41%. the C3c levels in plasma correlated well with disease severity in MG and GBS patients. Such a correlation was also evident in all CIDP patients except one that had persistent elevation in the presence of clinical improvement. Results suggest that the plasma C3c level may be useful for differentiating immune from non-immune mediated neurological diseases. Plasma C3c may also be used for monitoring disease severity, particularly in myasthenia gravis.     

Muscarinic M2 and M4 receptors in anterior cingulate cortex: relation to neuropsychiatric symptoms in dementia with Lewy bodies

Alterations in cholinergic functions have been reported to be associated with neuropsychiatric symptoms in dementia. Increased M1 muscarinic receptor binding in temporal cortex is associated with delusions in dementia with Lewy bodies (DLB) patients and increased M2/M4 receptor binding with psychosis in Alzheimer's disease. However, the relation between M2 and M4 muscarinic receptor and psychotic symptoms in DLB is unknown. The aim of this study was to measure M2 and M4 receptors in the anterior cingulate cortex in DLB and to correlate the neurochemical findings with neuropsychiatric symptoms. Muscarinic M2 and M4 receptor levels in the anterior cingulate cortex and adjacent cortex (Brodmann's area [BA] 32) were measured separately by using a radioligand binding protocol based on binding of [(3)H]AF-DX 384 in the presence and absence of dicyclomine, a potent M4 receptor antagonist. M2 receptor binding was significantly increased, while M4 receptor binding was unchanged in the cingulate cortex and BA32 of DLB patients compared with age-matched controls. Impaired consciousness was significantly associated with increased M4 binding and delusions were significantly associated with increased M2 binding. Increased M2 and M4 receptor binding in DLB was also associated with visual hallucinations. Upregulation of M2 and M4 muscarinic receptors in cingulate and adjacent cortex may thus contribute to the development of psychosis in DLB, with potential implications for treatments with drugs acting on these receptors.     

Nicotinic acetylcholine receptor immunohistochemistry in Alzheimer's disease and dementia with Lewy bodies: differential neuronal and astroglial pathology

Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are common forms of dementia in the elderly. The neuropathology of AD and DLB is related to cholinergic dysfunctions, and both alpha4 and alpha7 nicotinic acetylcholine receptor (nAChR) subunits are decreased in several brain areas in both diseases. In this immunohistochemical study, we compared neuronal and astroglial alpha4 and alpha7 subunits in AD, DLB and age-matched controls in the hippocampal formation. The numbers of alpha4 reactive neurons were decreased in layer 3 of the entorhinal cortex of AD and DLB, whereas those of alpha7 reactive neurons were decreased in layer 2 of the subiculum of AD and DLB and in layer 3 of the entorhinal cortex of DLB. In contrast, the intensity of alpha7 reactive neuropil was significantly higher in AD than in controls or DLB in a number of areas of the hippocampus (CA3/4 and stratum granulosum), subiculum and entorhinal cortex. An increase in alpha7 immunoreactivity in AD was also associated with astrocytes. The number of astrocytes double-labelled with alpha7 and glial fibrillary acidic protein (GFAP) antibodies was increased in most areas of the hippocampus and entorhinal cortex in AD compared with controls and DLB. Increased astrocyte alpha7 nAChRs in AD may be associated with inflammatory mechanisms related to degenerative processes specific to this disease.     

Pregnancy in the broad ligament

Pregnancy in the broad ligament is a rare form of ectopic pregnancy, and one type of abdominal pregnancy. The diagnosis is seldom established before surgery. A 38-year-old, 11-week pregnant woman, gravida 3, para 2, presented with vaginal bleeding. She had undergone two cesarean sections 10 and 6 years earlier. Pregnancy in the right broad ligament was diagnosed from clinical and transvaginal ultrasonographic findings. Emergency laparotomy and excision of a pregnancy in the right broad ligament and right salpingectomy were performed. She was well at discharge and at the 6-week follow up. We suggest the use of clinical and ultrasonographic findings for the suspicion of pregnancy in the broad ligament.     

Posterior leukoencephalopathy following cisplatin,bleomycin and vinblastine therapy for germ cell tumor of the ovary

A 31-year-old female developed multiple episodes of grand mal seizures after combination chemotherapy with cisplatin, vinblastine and bleomycin for germ cell ovarian cancer stage Ic. The clinicoradiologic features in this patient were consistent with posterior leukoencephalopathy, which is a rare complication of chemotherapy. Seizures were controlled by the anticonvulsive agent Dilantin (Pfizer, Khet Klongtoey, Bangkok) and she returned home without any permanent neurologic deficits. Follow-up magnetic resonance imaging 2 weeks later showed complete resolution of the abnormalities. This syndrome has been previously reported following cisplatin-based chemotherapy. Physicians should remain alert to the potential hazards of chemotherapy to the central nervous system. Risks and benefits should be seriously considered before starting treatment.     

Radiographic outcomes following treatment of intrabony defect with guided tissue regeneration in aggressive periodontitis

Objectives

This study reports the radiographic analysis of a split-mouth, single-blinded, randomised controlled clinical trial which was designed to compare the efficacy of simplified papilla preservation flap (SPPF) with or without guided tissue regeneration (GTR) in patients with aggressive periodontitis (AgP).

Methods

Eighteen AgP patients who had similar bilateral intrabony defects were treated. In all patients, the defects presented with radiographic evidence of an intrabony defect ≥3 and ≥5 mm of periodontal pocket depths (PPD). The surgical procedures included access for root instrumentation using SPPF alone (control) or, after debridement, a placement of resorbable GTR membrane (test). The standardised radiographic assessments were carried out at pre-surgical baseline and at 6 and 12 month post-surgery. Radiographic linear measurements and subtraction radiography were used as the method of analysis.

Results

Both treatments showed significant improvements in linear radiographic bone fill and defect resolution at 6 and 12 months, compared to baseline. The 12-month subtraction radiography at the GTR sites showed a significant improvement compared to the 6-month outcomes.

Conclusions

Both therapies were effective in the treatment of intrabony defects in AgP patients although no significant differences between them could be demonstrated. The finding that the bone fill and resolution of the defect at the GTR sites were significantly higher at 12 months than at 6 months after treatment indicates that bone regeneration is still an ongoing process at 6 months post-surgery.

Clinical relevance

Radiographic assessment of periodontal regeneration should be carried out at 12 months post-surgery in order to evaluate the complete healing of the bony defect.

     

Alteration in cytoadherence and rosetting of Plasmodium falciparum- infected thalassemic red blood cells

Hemoglobinopathies have a protective role in malaria that appears to be related to alterations in red blood cell (RBC) properties. Thalassemic RBCs infected with Plasmodium falciparum showed greatly reduced cytoadherence and rosetting properties as well as impaired growth and multiplication. A significant decrease in the levels of falciparum antigens associated with the membrane of infected beta-thalassemic RBCs was observed at trophozoite/schizont stage, but not young ring stage. This reduction was shown when a cytoadherence inhibitory monoclonal antibody, but not a noninhibitory pooled immune serum, was used. These observations suggest that protection against malaria in thalassemia is caused by both reduced parasitemias and altered adherence properties of the infected thalassemic RBCs that promote enhanced clearance of the parasite from the circulation.     

HIV-1 Protein gp120 Induces Mouse Lung Fibroblast-to-Myofibroblast Transdifferentiation via CXCR4 Activation

BackgroundIndividuals with HIV have ～2-fold increased risk of developing pulmonary fibrosis. The mechanism(s) by which this occurs has yet to be determined. HIV-1 protein gp120 activates CXCR4 in the lymphocyte, promoting a variety of intracellular signaling pathways including those common to TGFβ1 associated with lung fibroblast-to-myofibroblast transdifferentiation. We hypothesized that gp120 promotes pulmonary fibrotic changes via activation of CXCR4 in the lung fibroblast.MethodsMouse primary lung fibroblasts (PLFs) were cultured ± gp120, then analyzed for α-SMA expression and stress fiber formation. In parallel, PLFs were cultured ± gp120 ± AMD3100 (a CXCR4 antagonist), and α-SMA, pan and phospho-Akt, and total and phospho-MAPK (or ERK1/2) protein expression was quantified. Finally, lungs and PLFs from wild-type and HIV-1 transgenic mice were analyzed for hydroxyproline and α-SMA content.Resultsgp120 treatment increased α-SMA expression and myofibroblast differentiation in PLFs. gp120 treatment activated phosphorylation of ERK1/2, but not PI3K-Akt. Pretreatment with AMD3100 inhibited gp120-induced ERK1/2 phosphorylation and gp120-induced α-SMA expression. In parallel, there was a significant increase in hydroxyproline content in lungs from older HIV-1 transgenic mice and a >3-fold increase in α-SMA expression in PLFs isolated from HIV-1 transgenic mice.Conclusionsgp120 induces α-SMA expression and fibroblast-to-myofibroblast transdifferentiation by activating the CXCR4-ERK1/2 signaling pathway in mouse PLFs. Lungs of older HIV-1 transgenic mice contain higher hydroxyproline content and their PLFs have a striking increase in α-SMA expression. These results suggest a mechanism by which individuals with HIV are at increased risk of developing pulmonary fibrotic changes as they age.     

Rosetting of Plasmodium falciparum required multiple components of the uninfected erythrocytes

The mechanism of rosette formation of uninfected erythrocytes with Plasmodium falciparum-infected erythrocytes is rarely described. In this study, rosetting of uninfected normal erythrocytes with infected erythrocytes significantly reduced after treatment of the uninfected erythrocytes with neuraminidase. In contrast, the rosetting property of the infected erythrocytes was abolished by trypsinization but not by neuraminidase. The in vitro rosetting model showed that uninfected thalassemic erythrocytes poorly formed rosettes with infected normal erythrocytes when compared with normal erythrocytes of the same blood group. A rosetting parasite clone showed significant reduction in rosetting with thalassemic erythrocytes of all blood groups, however, this reduction was not obvious when the wild P. falciparum isolates were studied. These results suggest that while parasites from a single clone can rosette with uninfected erythrocytes via carbohydrate component, there is more than one type of receptor on uninfected erythrocytes involved in rosette formation with the heterogeneous populations of the wild P. falciparum isolates.