Synthesis of Resolvin E1 and Its Conformationally Restricted Cyclopropane Congeners with Potent Anti-Inflammatory Effect

RvE1 (1) is an endogenous lipid mediator with very potent anti-inflammatory activity, which is due to the inhibition of neutrophil chemotaxis and inflammatory cytokine production and the promotion of macrophage phagocytosis. On the basis of the conformational analysis of RvE1, we designed its four cyclopropane congeners (2a–d), in which the conformationally flexible terminal C1–C4 moiety of RvE1 was rigidified by introducing stereoisomeric cyclopropanes. The four congeners and also RvE1 were efficiently synthesized via a common synthetic route. The evaluation of the anti-inflammatory effects of the compounds in mice resulted in the identification of trans-β-CP-RvE1 (2d), which was significantly more active than RvE1, as a potential lead for anti-inflammatory drugs of a novel mechanism of action.     

Outcome of surgery for rheumatoid cervical spine at one institute over three decades

Background contextSurgical intervention is a therapeutic choice for atlantoaxial subluxation (AAS), vertical subluxation (VS), and subaxial subluxation (SAS) associated with rheumatoid cervical spine. However, the long-term outcomes of different subgroups remain unclear, although rheumatoid arthritis (RA) is a progressive disease even after surgery.PurposeTo evaluate the outcomes of surgery for various subgroups of rheumatoid cervical spine, performed at a single institute over three decades.Study designRetrospective clinical analysis.Patient sampleOne-hundred eighteen seropositive RA patients treated at one institute over the past three decades. Atlantoaxial fixation was performed in 28 AAS patients. Occipitospinal fusion was performed in 41 irreducible AAS or VS patients. Laminotomy with autologous bone fusion was performed in 22 patients, anterior fusion in 5, laminoplasty in 4, and posterior decompression/fusion with instrumentation in 12 with SAS.MethodsClinical outcomes using the Japanese Orthopedic Association score, complications, deterioration of RA, and mortality rate during the follow-up were investigated from preoperation to more than 10 years after surgery in the subgroups.Outcome measuresOutcomes were compared among the subgroups.ResultsPatients with AAS exhibited significantly better clinical outcomes throughout the follow-up period compared with patients from the other subgroups. Patients with SAS had the worst neurologic status even at preoperation, and the symptomatic improvement achieved by surgery deteriorated within less than 5 years. Deterioration of outcome was caused by occurrence of complications and deterioration of RA during the follow-up. The mortality rates at 5 and 10 years after surgery were 20% and 33%, respectively.ConclusionsThe outcome of surgery for rheumatoid cervical spine was different in the various subgroups and associated with the occurrence of complications and deterioration of RA.     

Usual interstitial pneumonia following resolution of cavitated pulmonary masses in a patient with ANCA‐associated vasculitis

A 72‐year‐old woman with slight pulmonary interstitial reticular markings was initially diagnosed with microscopic polyangiitis (MPA). Two years later, cavitated pulmonary masses appeared, and a biopsy specimen revealed granulomas. Granulomatosis with polyangiitis (GPA) was diagnosed. The masses resolved with treatment. Ten years later, the usual interstitial pneumonia (UIP) pattern appeared on chest computed tomography (CT). The diagnosis of lung toxicity from methotrexate (MTX) or cyclophosphamide (CYC) was precluded by the clinical course. Despite treatment with prednisolone (PSL), the UIP progressed. The change of pulmonary pathology from masses to UIP is rare in patients with GPA.     

Optimal reconstruction of left ventricular outflow tract obstruction before surgical myectomy in a case with hypertrophic obstructive cardiomyopathy

We present optimally reconstructed three‐dimensional computed tomography images of left ventricular outflow obstruction, comprehensive left ventriculography, and comparable intraoperative transesophageal echocardiography, as well as serial operative pictures, to facilitate the understanding of live‐heart anatomy of hypertrophic obstructive cardiomyopathy. As shown in this case, detailed morphological analysis around the left ventricular outflow tract using preoperative computed tomography would be feasible and useful. The present case highlights the importance of obtaining complete three‐dimensional information present in the acquired computed tomography dataset because computed tomography is not entirely noninvasive or free of radiation exposure and contrast material.     

Use of everolimus-eluting stent with a bioresorbable polymer coating for treatment of recurrent in-stent restenosis

Recently, an everolimus-eluting stent utilizing a bioresorbabale PLA polymer coating to release the agent everolimus has proven safe and effective in preventing restenosis for up to six months in de novo coronary arteries. But the use of a bioresorbable polymer-coated everolimus-eluting stent for in-stent restenosis lesions has not been previously investigated. This is a case report of one-year angiographic follow-up results after the implantation of a bioresorbable PLA polymer-coated everolimus-eluting stent for the treatment of recurrent in-stent restenosis. The case involved a 63-year-old female who had repeatedly presented with recurrent in-stent restenosis in the LCX. We successfully treated this recurrent ISR lesion by using a bioresorbable PLA polymer-coated everolimus-eluting stent; the one-year follow-up angiography revealed prevention of ISR after the implantation of this device.     

Osteoclastic function is accelerated in male patients with type 2 diabetes mellitus: the preventive role of osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG) on the decrease of bone mineral density

To clarify the pathogenesis of altered bone metabolism in diabetic state and its underlying mechanisms, the bone mineral content and fasting levels of serum intact parathyroid hormone (i-PTH), intact osteocalcin (i-OC), tartrate-resistant acid phosphatase (TRAP) and osteoclastgenesis inhibitory factor/osteoprotegerin (OCIF/OPG) were measured in male type 2 diabetic patients and their age-matched controls. In addition, urine levels of osteoclastic markers, C-telopeptide of type I collagen (CTx), deoxypyridinoline (DPD), and N-telopeptide of type I collagen (NTx) were simultaneously determined. Serum levels of i-PTH and i-OC in diabetic patients were significantly lower than those in the controls. Conversely, serum concentrations of TRAP were significantly elevated in diabetic patients. However, no clear correlation was observed between serum i-OC and TRAP. It was also observed that urinary excretion of CTx, DPD, and NTx was significantly increased in the diabetics as compared with the controls. Unexpectedly, serum levels of OCIF/OPG tended to be higher in the diabetic group, and these values exhibited a significantly positive correlation with those of serum TRAP. There was found a significantly negative correlation between serum TRAP and bone mineral density (BMD) and also between serum OCIF/OPG and bone mineral density. It seems probable that OCIF/OPG has a suppressive role on the increased bone resorption to prevent further loss of the skeletal bone mass in type 2 diabetic patients.     

The c protein fractions of group B streptococci: its distribution and relation to heat-labile antigens for the agglutination method

Distribution of the c protein fractions of group B streptococci and relation to heat-labile antigens for agglutination were investigated. The results were summarized as follows: 1. Analysis of antigenicity of the c protein in group B streptococcal strains isolated revealed that 74% of the type Ia/c strains carried only alpha antigen, and 76% of the type Ib/c strains contained both alpha and beta antigens. Component of the c protein fractions in most of type Ia/c strains isolated was different from that in reference strains. 2. Of 37 Ia/c alpha strains, 45.9% were determined non-typable, 32.4% were Ia/W, 13.5% were Ia/S, and 8.1% were Ia/Q in the agglutination for heat-labile antigens. Of 8 Ia/c alpha beta strains, 87.5% were Ia/Q, and 12.5% were Ia/SW. Of 5 Ia/c beta strains, 60% were Ia/Q, and 40% were Ia/QW. Of 19 Ib/c alpha beta strains, 68.4% were Ib/-, and 31.6% were Ib/S. Of 5 Ib/c alpha strains, 60% were Ib/-, and 40% were Ib/S. One Ib/c beta strain was Ib/-. 3. Because trypsin-sensitive portions of the beta antigens were lost, preparation of antigens for agglutination by pancreatic digestion could not exactly reflect results of the precipitation method.