The pronase resistance of cholesterol-nucleating glycoproteins in human bile

BACKGROUND & AIMS: Many putative pronucleating proteins have been isolated from the biliary concanavalin A (con A)-binding fraction. The pronase resistance of the overall nucleating-promoting activity was almost never taken into consideration. The aim of this study was to identify the major pronase-resistant con A-binding glycoproteins. METHODS: Pronase-treated and -untreated con A-binding glycoproteins were separated on a Superose 12 gel permeation column (Pharmacia, Uppsala, Sweden) and tested in a crystal growth assay. Proteins were identified by amino-terminal sequencing. RESULTS: Con A-binding pronucleating activity eluted in two peaks on the Superose column. This activity was unaltered after pronase treatment. Activity peak I contained too little protein to allow amino-terminal sequencing. In activity peak II, the major pronase-resistant con A-binding glycoproteins were identified as alpha 1-antitrypsin and alpha 1- antichymotrypsin. The 130-kilodalton nucleation promoter was identified as aminopeptidase N, but the full pronase resistance of this protein, reported earlier, was not confirmed. Immunoabsorptive removal of alpha 1-antitrypsin and alpha 1-antichymotrypsin and immunopurification showed that only alpha 1-antichymotrypsin had pronucleating activity. CONCLUSIONS: The pronase resistance of the nucleating-promoting activity of the con A-binding glycoprotein fraction was confirmed. An important part of this activity could be attributed to alpha 1- antichymotrypsin. It is an acute-phase protein, as are many other pronucleating proteins, which might indicate a general mechanism of action in gallstone formation. (Gastroenterology 1996 Jun;110(6):1926-35)     

Evaluation of Vitreous Substitutes in Managing Complicated Vitreo-retinal Surgeries

Background

Vitreous substitutes presently in use for intraoperative tamponade are perfluorocarbon liquids (PFCL) and for post operative tamponade are silicon oil (SO), sulphur hexafluoride (SF₆) and perfluorocarbon gas (PFC). Several factors are important for a thorough understanding of each of these vitreous substitutes. The absorption or necessity for removal, indications for use (including clinical studies and special surgical methods), additives and complications of use have to be considered.

Methods

Three port standard pars plana vitrectomy was performed in 60 consecutive cases requiring intra-vitreal intervention. PFCL was used intra-operatively in 30 cases (PFCL group and X group). The eyes were implanted with SO (silicon oil subgroup), PFC (C₃F₈ sub-group) and SF₆ (SF₆ sub-group) in twenty cases each. Apart from best corrected visual acuity (BCVA), the retinal status and the longevity of gas when used, changes and reaction in both the anterior and posterior segments were noted.

Result

The difference of postoperative BCVA in the PFCL and non-PFCL groups was statistically significant with p < 0.001. In both the PFCL and non-PFCL groups the difference between preoperative and postoperative BCVA was statistically significant with p < 0.0001. All three vitreous substitutes studied are effective given the case where they had been utilised.

Conclusion

PFCL is invaluable in the management of complicated retinal detachment (RD). Where a vitreous microsurgery is indicated, the visual outcome is good. SF₆ is useful for short-term tamponade. Silicon oil and C₃F₈ are useful for longer tamponade.Key Words: Tamponade, Perfluorocarbon liquids, Silicon oil, Sulphur hexafluoride, Perfluorocarbon gas, Retinal detachment     

Teriparatide Followed by Denosumab in Premenopausal Idiopathic Osteoporosis: Bone Microstructure and Strength by HR-pQCT

Premenopausal women with idiopathic osteoporosis (PreMenIOP) have marked deficits in skeletal microstructure. We have reported that sequential treatment with teriparatide and denosumab improves central skeletal bone mineral density (BMD) by dual-energy X-ray absorptiometry and central QCT in PreMenIOP. We conducted preplanned analyses of high-resolution peripheral quantitative computed tomography (HR-pQCT) scans from teriparatide and denosumab extension studies to measure effects on volumetric BMD (vBMD), microarchitecture, and estimated strength at the distal radius and tibia. Of 41 women enrolled in the parent teriparatide study (20 mcg daily), 34 enrolled in the HR-pQCT study. HR-pQCT participants initially received teriparatide (N = 24) or placebo (N = 10) for 6 months; all then received teriparatide for 24 months. After teriparatide, 26 enrolled in the phase 2B denosumab extension (60 mg q6M) for 24 months. Primary outcomes were percentage change in vBMD, microstructure, and stiffness after teriparatide and after denosumab. Changes after sequential teriparatide and denosumab were secondary outcomes. After teriparatide, significant improvements were seen in tibial trabecular number (3.3%, p = 0.01), cortical area and thickness (both 2.7%, p < 0.001), and radial trabecular microarchitecture (number: 6.8%, thickness: 2.2%, separation: −5.1%, all p < 0.02). Despite increases in cortical porosity and decreases in cortical density, whole-bone stiffness and failure load increased at both sites. After denosumab, increases in total (3.5%, p < 0.001 and 3.3%, p = 0.02) and cortical vBMD (1.7% and 3.2%; both p < 0.01), and failure load (1.1% and 3.6%; both p < 0.05) were seen at tibia and radius, respectively. Trabecular density (3.5%, p < 0.001) and number (2.4%, p = 0.03) increased at the tibia, while thickness (3.0%, p = 0.02) increased at the radius. After 48 months of sequential treatment, significant increases in total vBMD (tibia: p < 0.001; radius: p = 0.01), trabecular microstructure (p < 0.05), cortical thickness (tibia: p < 0.001; radius: p = 0.02), and whole bone strength (p < 0.02) were seen at both sites. Significant increases in total vBMD and bone strength parameters after sequential treatment with teriparatide followed by denosumab support the use of this regimen in PreMenIOP. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Psoriasis in childhood and adolescence: evaluation of demographic and clinical features

BACKGROUND: The present study was aimed to define the gender ratio, familial occurrence, age of onset, precipitating factors, clinical types, nail and joint involvement of psoriasis in childhood and adolescence in Turkey. METHODS: A total of 61 children with psoriasis under 18 years old were evaluated retrospectively, for age, gender, age of disease onset, family history, concomitant disease, the clinical type of psoriasis, clinical localization, nail and joint involvement and treatment modalities. RESULTS: Of the patients, 23 (37.70%) were boys and 38 (62.30%) were girls. Mean age was 9.28 +/- 4.02 years in girls and 11.18 +/- 3.85 years in boys (9.96 +/- 4.03 years in all children). Mean age at the onset of the disease was 6.81 +/- 4.11 years in girls and 7.03 +/- 4.28 years in boys (6.89 +/- 4.14 years in all patients). In 14 (23%) cases, a positive family history was detected. The most frequent probable triggering factors were upper respiratory tract infections (14.8%) and positive throat culture for A group ss-hemolytic streptococcus (21.3%). Frequency of emotional stress and psychiatric morbidity were 54% and 9.8%, respectively. The most frequent localizations at onset were trunk (44.3%), extremities (54.0%), and scalp (36.0%). Three children (4.9%) had a history of dissemination from psoriatic diaper rash. In total, 51 (83.6%) patients presented with psoriasis vulgaris, eight (13.1%) with generalized pustular psoriasis, and the remaining two (3.3%) with erythrodermic psoriasis. CONCLUSION: The incidence of psoriasis among dermatological patients in childhood and adolescence was 3.8%. The disease tends to appear earlier in girls than boys. The authors suggested that stress and upper respiratory infections are the most important triggering factors in childhood and adolescence psoriasis.