Physical Stability and Protein Stability of Freeze-Dried Cakes During Storage at Elevated Temperatures

The relationship between physical stability of freeze-dried cakes and protein stability during storage was studied using -galactosidase as a model protein and inositol as an excipient. Amorphous samples freeze-dried from solutions containing the enzyme and various concentrations of inositol in sodium phosphate buffer (50 mM, pH 7.4) were stored for 7 days over P₂O₅ at 40 to 70°C. Structural collapse and inositol crystallization were observed in some of the samples, depending on the formulation and storage temperature. The physical stability of freeze-dried samples was also studied by differential scanning calorimeter (DSC). Inositol showed a protein-stabilizing effect when its amorphous form was retained during storage, regardless of structural collapse. However, crystallization of inositol during storage removed its stabilizing effect. Addition of water-soluble polymers such as dextran, Ficoll and carboxymethyl cellulose sodium salt (CMC-Na) preserved activity of the enzyme by preventing inositol crystallization.     

Basiparallel cut by pneumoencephalotomography and cerebellar atrophy

Summary The basiparallel cut is a nearly horizontal slice of the posterior fossa used in air study and the structures are observed on a plane parallel to the clivus. Total shrinkage of the cerebellum, with or without fourth ventricle dilatation, was found in cases of olivopontocerebellar atrophy, some intoxications, and a few senile subjects. Some atrophy of paleocerebellar portions was seen in Holmes-type degeneration. Another pattern was symmetric shrinkage of neocerebellar lobules and relatively specific for the cases of multiple system atrophy such as progressive supranuclear palsy, striatonigral degeneration, Marie's ataxia, etc. Loss of the superior cerebellar peduncle was clearly demonstrated in this view.     

根据日本乡村绝经后妇女腰椎骨密度的随访研究制定骨质疏松的护理卫生方针

为了检测妇女绝经后发生骨量减少的相关指标进而倡导依据生活方式的特点对绝经后妇女骨质疏松的发生采取相应的预防和护理方针，我们对日本乡村的绝经后妇女（末次月经后六个月或更长时间算起）进行了为期4a的随访。我们运用双能X线骨密度仪（DXA）对腰椎骨密度（BMD）进行检测并对各种变量，包括年龄、绝经时的年龄、骨折史、日常摄奶量以及吸烟习惯进行多元分析，结果表明这些因素对于腰椎骨密度（BMD）的恢复是不相关联的。 在这些变量中，骨折史被证明对于相关人群是最具危险性的，这些对象有高比例的骨量减少（6．6％），其次是不规律的摄奶（13．6％）和吸烟（9．3％）。在护理中使用的作用于足跟骨的检测骨密度的设备被证实与作用于腰椎的DXA设备可以相互替代。依据这些结果，针对居住在日本乡村的绝经后妇女制订了相应的预防骨质疏松的方针。这些卫生指导方针依据特定区域的生活方式而制定并可适用于其他的人群和区域。在本文中，作者列出了不同的有助于预防绝经后妇女出现骨质疏松的方法并进行了调查。     

Successful Treatment of γ-Heavy-Chain Disease with Rituximab and Fludarabine

An 84-year-old Japanese man was admitted because of pancytopenia. The bone marrow was hypoplastic with a predominance of abnormal small lymphocytes and grape cells, which were positive for CD19 and CD20, and partially for the surface ?-light chain. Systemic CT scanning showed neither lymph node swelling nor hepatosplenomegaly. Serum immunoelectrophoresis and rocket immunoselection assays showed the presence of monoclonal IgG protein without a corresponding light chain and faint IgM? monoclonal protein. Histologic analysis of the clot preparation of the bone marrow aspirate facilitated a diagnosis of lymphoplasmacytic lymphoma (LPL). PCR analysis of the marrow cells demonstrated a clonal rearrangement of the immunoglobulin heavy-chain gene. From these results, we made a final diagnosis of γ-heavy-chain disease (γ-HCD) with underlying LPL localized in the bone marrow. We performed only a single course of immunochemotherapy (rituximab and fludarabine) in view of severely impaired hematopoiesis, which resulted in marked reduction of lymphoma cells and improvement of hematopoiesis. This report suggests the efficacy of rituximab plus fludarabine therapy for LPL-associated γ-HCD.     

Humoral immunity patterns based on antibody reactivity to rotavirus antigens in Brazilian children under 5 years of age

The age distribution of antibody to simian rotavirus (SA-11) was studied in serum specimens obtained from 399 children aged to 5 years and living in the city of Recife (PE), located in the north eastern region of Brazil. Sera were examined for group-specific rotavirus antibody using a blocking enzyme immunoassay (bELISA) and a hemagglutination inhibition antibody (HIA) test, and for anti-VP2, anti-VP4, anti-VP6, and anti-VP7 antibodies using an immunoblotting assay (IBA). Antibody prevalence was similar in all bELISA and HIA assays, showing a steep rise in the 6- to 17-month-old age groups. The results indicate early acquisition of antibody to rotavirus. The majority of children aged 2 to 4 years had bELISA (50% to 60%) and HIA (70% to 81%) antibodies. There was an association in prevalence data obtained by HIA and bELISA with immunoblotting (IBA), revealing four serologic profiles. Children with profiles I and II (60%) respectively had HAI and ELISA antibody or HAI antibody alone and all had immunoprotective antibodies to VP4 and/or VP7. These children were regarded as “immune,” resembling convalescent patients with a rotavirus infection. Children with profile III (4%) had no HIA antibody and only non-protective anti-VP6 and/or VP7 antibody, and were considered to be “partially immune.” Children with profile IV (36%) had no detectable antibody and were classified as “nonimmune.” These children should be considered to be susceptible to rotavirus infection, with the risk of developing clinically severe diarrhea. © 1996 Wiley-Liss, Inc.     

The effect of remimazolam on postoperative memory retention and delayed regeneration in breast surgery patients: Rationale and design of an exploratory,randomized, open,propofol-controlled,single-center clinical trial: A study protocol

Background:Remimazolam, a benzodiazepine ultra-short-acting sedative, has been used in general anesthesia since August 2020. It is used in awake surgeries that require awakening the patient in the middle of the surgery because of its rapid awakening effect as well as antagonistic interactions. If remimazolam has associated anterograde amnesia similar to benzodiazepines, it will have a positive effect on preventing psychological trauma. However, to our knowledge, the effect of remimazolam on anterograde amnesia has not been previously examined.Methods/design:The aim of this exploratory, open, propofol-controlled, single-center, randomized clinical trial is to examine the effect of remimazolam on postoperative memory retention and delayed regeneration. Seventy patients undergoing breast surgery will be included in the study. The patients will be randomly assigned to receive propofol or remimazolam as sedatives during surgery. The primary endpoint is the number of posters patients remember 24 hours after surgery (among 4 posters shown after awakening from anesthesia) as an assessment of anterograde amnesia. Secondary endpoints are retrograde amnesia, dose of analgesic given from the time the patient returns to the ward until 24 hours after surgery, immediate postoperative pain numerical rating scale scores, and pain numerical rating scale scores 24 hours after leaving the operating room. Recruitment will take place between October 2021 and March 2022 to achieve the target sample size.Discussion:To our knowledge, this is the first trial designed to examine the effects of remimazolam on postoperative memory retention and delayed regeneration in patients undergoing breast surgery.Trial registration:This clinical trial was registered at the University Hospital Medical Information Network (UMIN) Center on September 28, 2021 (UMIN-CTR: UMIN000045593).     

Bilateral anterior optic neuritis in adult measles infection without encephalomyelitis

PURPOSE: To describe anterior optic neuritis in adult measles infection.DESIGN: Interventional case report. METHODS: A 31-year-old woman presented with bilateral visual loss 6 days after the onset of maculopapular rash. Complete ophthalmic and neurologic examinations, radiologic studies, and lumbar puncture were performed. RESULTS: Visual acuities were counting fingers in both eyes, with bilateral optic disk hyperemia and swelling noted. Neurologic examination was unremarkable, and computed tomography and magnetic resonance imaging of the brain were normal. The cerebrospinal fluid (CSF) was devoid of white cells, although measles immunoglobulin M (IgM) antibodies were detected in both CSF and serum. Intravenous corticosteroids were administered, and clinical findings resolved within 1 month. A fall in serum IgM and a rise in serum IgG titers were observed. CONCLUSIONS: Although rare, optic neuritis in the absence of encephalomyelitis may occur in measles. Whether treatment is effective is unknown.     

Unique uptake and transport of isoflavone aglycones by human intestinal caco-2 cells: comparison of isoflavonoids and flavonoids

Soy isoflavonoids have attracted much attention because of their estrogenic activity. To study the intestinal absorption of the isoflavonoids, we investigated the cellular uptake and metabolism of genistein and daidzein and their glucosides, genistin and daidzin, by Caco-2 cell monolayers as a model of the human intestinal epithelium. When Caco-2 monolayers were incubated with genistein or daidzein at 10 micromol/L from the apical (mucosal) side, aglycone was lost from the apical solution for 2.0 h (P < 0.05) and the glucuronide/sulfates appeared at the level of 1-2 micromol/L. In the basolateral (serosal) solution, both intact aglycones and their glucuronide/sulfates increased (P < 0.05) with time and reached approximately 20 and 15% of the initial dose, respectively. The transport of their glucosides, genistin and daidzin, through Caco-2 monolayers was less than one tenth that of the aglycones. The cellular metabolism of genistein was compared with quercetin, kaempferol, luteolin and apigenin. Only genistein aglycone was transported intact to the basolateral solution. Transport was greater (P < 0.05) than that of flavonoid aglycones and was without an appreciable decrease of transepithelial resistance. Radical scavenging activity was not related to the susceptibility to conjugation of flavonoids/isoflavonoids. Affinity to the liposomal membrane was increased in the order of genistin = daidzin < daidzein < genistein < flavonoid aglycones. These results strongly suggest that isoflavone aglycones are taken up into enterocytes more efficiently than their glucosides because of their moderate lipophilicity. Furthermore, they are generally transported to the basolateral side in intact form in contrast to flavonoids, probably due to their unique isoflavonoid structure.