A study on flow properties of semisolid dosage forms

There are a wide variety of semi-solid ointments used for healing the skin diseases, whose therapeutic and skin penetration abilities may greatly differ from one another depending on the compositions of ointment vehicles. A computer optimization technique was applied to obtain the optimum formula of o/w type ointment giving the in vitro maximum absorption rate through hairless rat skin membrane. Some of the formulations were selected to find out a relationship between skin penetration of ointment and its rheological characteristics. The experimental value of absorption rate obtained from the ointment by optimum formula agreed well with the theoretical value obtained from a polynomial regression analysis. Three kinds of ointments selected among 15 formulations were obtained with a concentric cylinder type rheometer (Model; Rheolab SM-HM Physica, Germany) at 20, 30, 40 and 50°C for rheograms of rhelolgical properties of o/w type ointments. As the temperature was raised, all products showed a decrease in both shear stress and yield values. The higher skin penetration, the lower shear stress showed.     

No news is not good news: information preferences of patients with cancer

Many patients express dissatisfaction with clinicians' information-giving. When the information is complex or potentially upsetting, clinicians may deliberately withhold information, especially if they lack the skills to handle patients' emotional reactions. Others underestimate the amount of information patients require. In this study, a heterogeneous sample of 101 patients participating in a trial assessing the benefits of receiving audio-taped recordings of their ‘bad news’ consultations, completed a questionnaire similar to Cassileth's Information Styles Questionnaire. This questionnaire assessed patients' preferences for both general and specific information about their disease and its treatment. Of the sample, 94% expressed a desire for as much information as possible from their oncologist, be it good or bad; 4% wished for information only if it was good news and 2% declined extra information, preferring to leave things up to the doctor. Patients wanting less specific or no extra information were older and had poorer prognoses than those wanting full disclosure. Although precise information needs varied between patients, this study showed that patients with cancer in general wish to be well-informed about diagnosis, prognosis, therapeutic options and side-effects.     

Effects of a Medical Aid program on medical utilization patterns for low-income patients with affective disorder in Seoul

Mental illness has been increasing globally and its global burden of disease has reached a significant level, and urban dwellers have more chances of having worse mental health status due to high population density, isolated social networks. In Korea''s medical security system, Medical Aid (MA) program and National Health Insurance (NHI), patients covered by MA pay much smaller out-of-pocket payments for outpatient services because of exempt from hospitalization fees. However, as a result of focusing on improving access to medical services for the urban poor due to lower out-of-pocket payment, their healthcare costs have greatly increased, while their health management has thus far been inadequate. In light of the background, this study investigated the differences in patterns of medical utilization among affective disordered patients covered by the MA program and the NHI system respectively.Data used for this study were extracted from customized health information data from the National Health Insurance Service (NHIS). The data source used in this study, customized claims data from the NHIS, is census data, which strengthens the representativeness and reliability of the study results. A total of 6754 inpatients (MA: 3327 and NHI 20%: 3327) diagnosed with the affective disorder were retrieved by Propensity Scores Matching (PSM).The length of stay of MA beneficiaries was found to be longer than that of NHI enrollees. However, the rate of hospital emergency room visits by NHI enrollees was higher than that of MA beneficiaries.Overall, community-based interventions are required to prevent and treat mental health by providing primary medical care in the community, and linking with mental health centers. Such policies will ultimately improve the financial sustainability of medical security systems.     

Lysosomal cathepsin D mediates endogenous mucin glycodomain catabolism in mammals

Mucins are functionally implicated in a range of human pathologies, including cystic fibrosis, influenza, bacterial endocarditis, gut dysbiosis, and cancer. These observations have motivated the study of mucin biosynthesis as well as the development of strategies for inhibition of mucin glycosylation. Mammalian pathways for mucin catabolism, however, have remained underexplored. The canonical view, derived from analysis of N-glycoproteins in human lysosomal storage disorders, is that glycan degradation and proteolysis occur sequentially. Here, we challenge this view by providing genetic and biochemical evidence supporting mammalian proteolysis of heavily O-glycosylated mucin domains without prior deglycosylation. Using activity screening coupled with mass spectrometry, we ascribed mucin-degrading activity in murine liver to the lysosomal protease cathepsin D. Glycoproteomics of substrates digested with purified human liver lysosomal cathepsin D provided direct evidence for proteolysis within densely O-glycosylated domains. Finally, knockout of cathepsin D in a murine model of the human lysosomal storage disorder neuronal ceroid lipofuscinosis 10 resulted in accumulation of mucins in liver-resident macrophages. Our findings imply that mucin-degrading activity is a component of endogenous pathways for glycoprotein catabolism in mammalian tissues.

Mammalian cells append glycans to the majority of their secreted and cell surface proteins (1). These extracellular glycoproteins are broadly categorized as Asn-linked N-glycoproteins and Ser/Thr-linked O-glycoproteins, both of which are typically elaborated into branching structures with many monosaccharide units strung together. Therefore, catabolism of a given extracellular protein typically involves hydrolase-mediated breakdown of both its peptide backbone and one or more complex glycans.Much of our current understanding of glycoprotein catabolism arises from the study of human mutations that cause N-glycoprotein degradation pathways to go awry. Analysis of accumulation products in lysosomal storage disorders such as mannosidosis, aspartylglucosaminuria, sialidosis, Schindler (types I and II), galactosialidosis, and fucosidosis have provided a framework to understand N-glycoprotein catabolism (2). In brief, N-glycoproteins are extensively proteolyzed such that there are free alpha carboxyl and amino groups on the asparagine residue bearing the glycan. After fucose is removed by lysosomal α-L-fucosidase, N-glycanase aspartylglucosaminidase hydrolyzes the glycan-peptide bond. The free glycan can then be broken down from both reducing and nonreducing ends by a variety of hydrolases (2).Lysosomal degradation of O-glycoproteins is understudied relative to that of N-glycoproteins, in part due to unique difficulties associated with structural analysis of O-glycopeptides (3), and is typically assumed to occur analogously to N-glycoprotein catabolism (2, 4). Mucins are a class of extracellular O-glycoproteins that have challenged this assumption. Mucins are characterized by repeating domains bearing a high frequency of N-acetylgalactosamine (GalNAc)-linked serine and threonine residues, such that the biomolecule as a whole can exceed 50% glycosylation by mass (5). The densely spaced glycans in mucin glycodomains endow them with unique properties, including a rigid, extended secondary structure and resistance to proteolysis (6). As such, mucin catabolism has been suggested to proceed in the reverse order of N-glycan catabolism, involving removal of glycans followed by proteolysis of the peptide backbone (2), or through shedding from cell surfaces into luminal spaces (7). Meanwhile, major histocompatibility complex (MHC) I and MHC II peptides bearing mucin-type O-glycans have been repeatedly observed (8–11), indicating that mucin domains can, under some circumstances, be proteolyzed with their glycans intact.We and others have characterized proteases from the bacterial kingdom that cleave within densely O-glycosylated mucin domains without prior deglycosylation, termed mucinases (3, 12–14). The existence of bacterial mucinases indicates that access to the peptide backbone through densely spaced O-glycans is not impossible for a proteolytic enzyme. Given the biological ubiquity and clinical significance of mucins (15–20), we set out to systemically evaluate if mammals encode enzyme(s) with proteolytic activity toward glycosylated mucin domains. At the outset, we considered sequence and structure-based approaches to identify candidates from mammalian genome sequences. However, as bacterial mucinases share poor sequence homology (12, 21), we turned to a biochemical strategy.     

Effect of chitosan oligosaccharide on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced oxidative stress in mice

The abilities of two types of chitosan oligosaccharides, chitosan oligosaccharide I (1-kDa相似文献   

Long-term results of total hip arthroplasty with a cemented custom-designed swan-neck femoral component for congenital dislocation or severe dysplasia: a follow-up note

BACKGROUND: This follow-up study updates the results in a consecutive series of nineteen cemented total hip replacements with a swan-neck femoral component in patients with congenital dislocation or severe hip dysplasia. The series was previously reported on in 1993. METHODS: The patients were petite, with an average height of 152 cm and an average weight of 50 kg, and the femoral canals could not accommodate an off-the-shelf femoral component. Sixteen of the nineteen hips were available for follow-up at an average of 13.3 years (range, eleven to twenty years). Fourteen hips had up-to-date clinical and radiographic examinations. RESULTS: At the time of the latest follow-up, thirteen hips were rated as excellent; two, as good; and one, as a failure because of loosening of both components requiring revision eleven years after the index operation. Another hip required acetabular revision because of loosening fifteen years after the index operation. The rates of femoral and acetabular component revision were 6% and 12.5%, respectively. Radiographic analysis demonstrated that no femoral component was loose. One cup was definitely loose at 19.5 years, and three cups were possibly loose at an average of fourteen years. The radiographic rate of acetabular loosening was 33%. The total rate of cup failure (radiographic loosening and revision) was 43%. CONCLUSIONS: The excellent clinical and radiographic results associated with the swan-neck femoral component, and the 94% rate of survival, at an average of 13.3 years (range, eleven to twenty years) indicate that the biomechanical objectives of this custom-designed prosthesis for patients with congenital dislocation or severe hip dysplasia were met. On the basis of this favorable long-term experience, we still use this prosthesis when the anatomic abnormality cannot be adequately addressed by use of a commercially available prosthetic component.     

Structural identification of skin ceramides containing ω-hydroxy acyl chains using mass spectrometry

The stratum corneum (SC) acts as a barrier that protects organisms against the environment and from transepidermal water loss. It consists of corneocytes embedded in a matrix of lipid metabolites (ceramides, cholesterol, and free fatty acids). Of these lipids, ceramides are sphingolipids consisting of sphingoid bases, linked to fatty acyl chains. Typical fatty acid acyl chains are composed of α-hydroxy fatty acids (A), esterified ω-hydroxy fatty acids (EO), non-hydroxy fatty acids (N), and ω-hydroxy fatty acids (O). Of these, O-type ceramides are ester-linked via their ω-hydroxyl group to proteins in the cornified envelope and can be released and extracted following mild alkaline hydrolysis. Tandem mass spectrometry (MS/MS) analysis of O-type ceramides using chip-based direct infusion nanoelectrospray-ion trap mass spectrometry generated the characteristic fragmentation pattern of both acyl and sphingoid units, suggesting that this method could be applied to the structural identification of O-type ceramides. Based on the MS/MS fragmentation patterns of O-type ceramides, comprehensive fragmentation schemes are proposed. In addition, we have also developed a method for identifying and profiling O-type ceramides in the mouse and guinea pig SC. This information may be used to identify O-type ceramides in the SC of animal skin.     

七氟烷对大鼠海马脑片缺氧损伤的保护作用

目的：应用离体大鼠海马脑片电生理记录技术，观察七氟烷对海马脑片在缺氧过程中突触后诱发群峰电位（PS）的时相以及复氧后幅度变化的影响，探讨七氟烷对脑组织缺氧损伤的保护作用。方法：实验于2004-09／12在徐州医学院江苏省麻醉学重点实验室电生理研究室进行。大鼠乙醚麻醉后迅速断头取脑，低温分离海马，并沿矢状面将其切成0．5mm厚的脑片。实验分为缺氧组和七氟烷（1％，2％和4％）处理组。平衡灌注后，双脉冲方波刺激海马CA3区Schaffer侧支，记录海马CA1区锥体细胞的诱发群峰电位潜伏期和幅度作为基础值，所有取得基础值的脑片分别按上述分组进行实验。用通入95％N2和5％CO2混合气的人工脑脊液灌注脑片，实施缺氧，时间为5min。更换通入人工脑脊液的混合气为95％O2和5％CO2，实施复氧，时间120min。七氟烷在缺氧前10min给予，并维持在缺氧期间和复氧后10min，给药时间为25min。实验结束后各组取脑片四五片用TTC染色，酶标仪测定A490值，与空白对照值比较，分析脑片活性。结果：①与基础值相比，2％七氟烷可明显延长正常脑片诱发群峰电位出现的潜伏期（P〈0.05），不降低诱发群峰电位幅度；4％的七氟烷不延迟诱发群峰电位出现的潜伏期，但可显著降低诱发群峰电位的幅度（P〈0.05）。②与缺氧组相比，2％和4％七氟烷均明显延迟缺氧所致的诱发群峰电位消失时间（P〈0．05）；而4％七氟烷又可明显增加复氧后诱发群峰电位幅度的恢复率（P〈0．05），降低脑片TTC染色下降百分率，差异有显著性意义（P〈0.05）。结论：4％七氟烷可明显延迟海马脑片缺氧所致诱发群峰电位消失的时间，增加复氧后诱发群峰电位幅度的恢复率，具有抗缺氧损伤的神经保护作用。     

Usefulness of physical maneuvers for prevention of vasovagal syncope.

BACKGROUND: It is known that approximately two-thirds of patients with vasovagal syncope have prodromal symptoms and when these start, physical maneuvers that can increase venous return may abort the syncopal attack. The aims of this study were to evaluate the effects of 3 physical maneuvers, squatting, leg-crossing with muscle tensing, and handgrip, on improving hemodynamic status, and to compare the effect of each on aborting or preventing vasovagal syncope. METHODS AND RESULTS: Of 50 patients who underwent the head-up tilt test (HUT) to evaluate syncope, 27 patients with positive HUT were classified as group I (14 men, 13 women; mean age 44.5+/-15.3 years), 23 patients with negative HUT were classified as group II (13 men, 10 women; mean age 41.2 +/-16.7 years), and 21 normal subjects were classified as group III (10 men, 11 women; mean age 28.6+/-6.3 years). The effects of the physical maneuvers were evaluated in 21 patients from group I who underwent a repeat HUT 1 week after the initial test. Leg-crossing significantly increased systolic blood pressure (SBP) in all 3 groups (8.0+/-5.8 mmHg in group I, 7.0+/-8.5 mmHg in group II, 8.7+/-5.7 mmHg in group III; p < 0.05), but not diastolic blood pressure (DBP). Squatting significantly increased SBP and DBP in all 3 groups (7.1 +/-5.1, 4.6+/-5.8 mmHg in group I, 7.8+/-5.9, 4.3+/-4.7 mmHg in group II, 6.5+/-5.0, 3.7+/-3.9 mmHg in group III; p < 0.05). However, handgrip did not exert any significant influence on the hemodynamics in any group nor did heart rate change significantly during the physical maneuvers in any group. During the repeat HUT, prodromal symptoms with hypotension developed in 13 of the 21 patients and of these 5 fainted immediately after and were not able to do the physical maneuvers. Squatting and leg-crossing aborted syncope in 7 of 8 patients, but handgrip aborted syncope in only 1 patient. CONCLUSION: Squatting and leg-crossing with muscle tensing improved the hemodynamics of normal subjects as well as those of patients with vasovagal syncope. Squatting and leg-crossing can be used as a simple and effective preventive maneuver in patients with vasovagal syncope.     

Significance of 40-, 45-, and 48-kDa Proteins in the Moderate-to-Severe Clinical Symptoms of Buckwheat Allergy

Purpose

This study was aimed to investigate the relationship between the allergen components and moderate-to-severe allergic reactions in patients with buckwheat allergy.

Methods

Fifteen patients with a history of buckwheat ingestion and a buckwheat specific IgE level≥0.35 kU/L were enrolled. They were divided into 2 groups according to clinical severity scores, with 0-1 being asymptomatic-to-mild and 2-4 being moderate-to-severe symptoms. Immunoblotting was performed to investigate IgE reactivity toward buckwheat allergens and to measure intensity of each component by using a reflective densitometer.

Results

The proportions of positive band to the 16 kDa (62.5% vs 0%, P=0.026) and 40-50 kDa (87.5% vs 28.6%, P=0.041) buckwheat allergens in the grade 2-4 group were higher than those in grade 0-1 group. The level of buckwheat specific IgE of grade 2-4 group was higher than that of grade 0-1 group (41.3 kU/L vs 5.5 kU/L, P=0.037). The median optical densities (ODs) of IgE antibody binding to 40-50 kDa protein were higher in the grade 2-4 group, compared with those in the grade 0-1 group (130% OD vs 60.8% OD, P=0.037).

Conclusions

The 40-50 kDa protein is implicated as an important allergen to predict moderate-to-severe clinical symptoms in Korean children with buckwheat allergy.