Cannabinoids, loratadine and allopurinol as novel additions to the antipsoriatic ammunition

As the current antipsoriatic medications are commonly associated with deleterious side-effects, a determined search for safer agents, which could be used alone or in combination with current antipsoriatic drugs, would be very imperative. Psoriasis is believed to be characterized by a type 1 cytokine pattern; interferon-gamma, interleukin (IL)-2 and tumour necrosis factor (TNF)-alpha are predominantly expressed in this disorder. Nitric oxide, reactive oxygen species, histamine, leukotriene B4, and decreased [corrected] keratinocyte cyclic adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP) ratio are supposed to play roles in the pathogenesis of this disorder. Based on the immunopathogenesis of psoriasis, this paper introduces three novel, potential treatments for this clinical conundrum: (i) cannabinoids, which exert inhibitory effects on antigen processing and macrophage/T-cell interaction and also on the release of IL-2, TNF-alpha and nitric oxide from immune cells; (ii) loratadine, which is an antihistamine capable of increasing [corrected] the cAMP/cGMP ratio and the production of leukotriene B4; and (iii) allopurinol, which scavenges free radicals, inhibits the production of TNF-alpha, and downregulates the expression of intercellular adhesion molecule-1 and P2X7 receptors on monocytes/macrophages, which are involved in antigen presentation and production of the inflammatory response, respectively. Importantly, allopurinol, especially in combination with cyclosporin, has been shown to be effective against experimental autoimmune uveitis, which, like psoriasis, is a cell-mediated autoimmune disorder.     

Evidence that Wra and Wrb are antithetical

Studies on 24 Wr(a+b+) and 23 Wr(a-b+) blood samples, using anti-Wrb in the enzyme-linked antiglobulin test (ELAT), have shown that Wr(a+b+) red cells bind, on average, a little over half the amount of anti-Wrb bound by Wr(a-b+) red cells. Similarly, ELAT studies using six different anti-Wra and 10 Wr(a+b+) samples, as well as red cells from the original Wr(a+b-) proposita, have shown that Wr(a+b+) red cells bind about half the amount of anti-Wra bound by Wr(a+b-) red cells. Various pitfalls that can arise when the ELAT is used to measure antigen ratios on red cells have been avoided but are described. This conclusive evidence that Wra and Wrb have an antithetical relationship is discussed in light of the knowledge that a ficin-resistant portion of MN sialoglycoprotein (SGP), when carried in liposomes, can inhibit anti-Wrb. It is possible that Wra, Wrb, or both may encode a post-translational change in MN SGP, or production of transferases that glycosylate membrane lipids that affect in situ orientation of MN SGP, or production of protein band 3 that then forms a complex with MN SGP at the red cell membrane surface.     

大鼠脂肪间充质干细胞的成骨分化

目的:观察大鼠脂肪间充质干细胞经成骨诱导向成骨细胞分化的生物学特性,探讨其作为骨组织工程种子细胞的可行性。方法:实验于2004-07/2006-03在中南大学湘雅医院中心实验室完成主要工作。①取健康SD大鼠双侧腹股沟区脂肪垫,消化法分离出脂肪间充质干细胞,接种入含有体积分数为0.1的新生牛血清的低糖DMEM培养基进行原代培养。②取第3代的脂肪间充质干细胞,用含有体积分数为0.1的新生牛血清、0.1μmol/L地塞米松、50μmol/L抗坏血酸、10mmol/Lβ-甘油磷酸钠的高糖DMEM培养基诱导其向成骨细胞分化。③于3,5,7,10,12,14,21d分别采用倒置显微镜观察细胞形态及增殖情况、Gomori改良钙钴法碱性磷酸酶染色、茜素红S钙结节染色和Ⅰ型胶原免疫细胞化学染色检测脂肪间充质干细胞成骨分化的情况。结果:①脂肪间充质干细胞原代细胞呈成纤维细胞样长梭形外观,传代稳定,细胞形态均一。②经成骨诱导,脂肪间充质干细胞体积增大,呈多角形;成骨诱导14d,Gomori改良钙钴法碱性磷酸酶染色,细胞胞浆内可见浅棕色至棕黑色的颗粒,平均染色阳性率为80%;碱性磷酸酶活性随时间的延长而逐渐增高[3,5,7,10,12,14d依次为(2.43±0.09),(3.60±0.08),(5.01±0.09),(7.75±0.07),(9.59±0.09),(10.94±0.10)μkat/L];成骨诱导21d,钙结节形成明显,茜素红S染色,呈红色结节;成骨诱导7d,Ⅰ型胶原免疫细胞化学染色,细胞胞浆呈棕黄色,胞核经苏木精复染为蓝色。结论:大鼠脂肪间充质干细胞经成骨诱导具有成骨细胞的生物学特性,可作为骨组织工程的种子细胞。     

Management of Appendicitis Globally Based on Income of Countries (MAGIC) Study

Background

Our aim is to compare the management approaches and clinical outcomes of acute appendicitis according to annual Gross National Income per Capita (GNI/Capita) of countries.

Methods

Consecutive patients who were diagnosed to have acute appendicitis from 116 centers of 44 countries were prospectively studied over a 6-month period (April–September 2016). Studied variables included demography, Alvarado score, comorbidities, radiological and surgical management, histopathology, and clinical outcome. Data were divided into three groups depending on the GNI/Capita.

Results

A total of 4271 patients having a mean (SD) age of 33.4 (17.3) years were studied. Fifty-five percent were males. Two hundred and eighty patients were from lower–middle-income (LMI) countries, 1756 were from upper–middle-income (UMI) countries, and 2235 were from high-income (HI) countries. Patients in LMI countries were significantly younger (p?<?0.0001) and included more males (p?<?0.0001). CT scan was done in less than 8% of cases in LMI countries, 23% in UMI countries, and 38% in HI countries. Laparoscopy was performed in 73% of the cases in the HI countries, while open appendectomy was done in more than 60% of cases in both LMI and UMI countries (p?<?0.0001). The longest mean hospital stay was in the UMI group (4.84 days). There was no significant difference in the complication or death rates between the three groups. The overall death rate was 3 per 1000 patients.

Conclusions

There is great variation in the presentation, severity of disease, radiological workup, and surgical management of patients having acute appendicitis that is related to country income. A global effort is needed to address this variation. Individual socioeconomic status could be more important than global country socioeconomic status in predicting clinical outcome.

     

Characterization of hyperlipidemia in two patients with analbuminemia

The results of plasma lipid and lipoprotein analysis in two related patients, brother (R.U.) and sister (R.R.) with analbuminemia, and three first-degree relatives (parents and sister) are reported. Both patients showed a remarkable increase in cholesterol and phospholipid levels, and there was a corresponding increase in serum apo B and apo A-I. This hyperlipidemia is due to a selective increase in LDL and HDL concentrations. R.U. showed an increase in both HDL2- and HDL3-cholesterol, R.R. only in HDL3-cholesterol. VLDL concentration was reduced in R.U. and normal in R.R. The plasma lipoprotein electrophoretic pattern did not correspond to any of the phenotypes in Fredrickson's classification. Composition of the different lipoprotein fractions was normal in the patients and family members. Serum FFA level in R.R. was very low. An increase in the plasma protein fractions, particularly the transport fractions, was confirmed in both patients. The possible pathophysiology of the hypercholesterolemia in these patients is discussed. Unlike other reported cases, clinical signs of atherosclerotic complications were absent.     

Trichinella infection and clinical disease

Trichinellosis is caused by ingestion of insufficiently cooked meat contaminated with infective larvae of <it>Trichinella</it> species. The clinical course is highly variable, ranging from no apparent infection to severe and even fatal disease. We report two illustrative cases of trichinellosis. Returning to Denmark a few days after having eaten roasted pork in the Republic of Serbia, a female patient suffered from severe vomiting, epigastric pain, diarrhoea, and later myalgia, generalized oedema, and prostration. A biopsy showed heavy infestation with <it>Trichinella spiralis</it>, 2000 larvae/g of muscle. Life-threatening cardiopulmonary, renal and central nervous system complications developed. The patient recovered after several months. Her husband, who also ate the pork, did not have clinical symptoms, but an increased eosinophil count and a single larva in a muscle biopsy confirmed infection. The epidemiology, clinical manifestations, diagnosis, treatment and prevention of trichinellosis are reviewed.      

JMH variants: serologic, clinical, and biochemical analyses in two cases

BACKGROUND: JMH is a high-frequency red cell blood group antigen that resides on a 76- to 80-kDa glycosylphosphatidylinositol-linked protein also known as CDw108. Antibodies with JMH specificity are often autoimmune and are usually, if not always, clinically benign. Some individuals with JMH-variant antigen produce alloantibodies to JMH, but little evidence concerning their clinical significance is available. This article reports on two patients who express a JMH-variant antigen and produced alloanti-JMH. STUDY DESIGN AND METHODS: Murine monoclonal antibodies and human antibodies to JMH were used in hemagglutination, radioimmunoassay, and Western blot testing of red cells from two JMH- variant patients; antiserum from one of these patients was also used in biochemical studies. In addition, in vivo survival of JMH-positive red cells was studied in the same patient. RESULTS: Biochemically, both examples of red cells with the JMH-variant phenotype expressed a JMH protein with a molecular weight similar to that of the normal JMH protein. For both patients, family studies suggested an autosomal recessive pattern of inheritance. Survival study demonstrated reduced in vivo red cell survival in one patient. CONCLUSION: JMH-variant phenotypes express a protein of normal molecular weight and are inherited in an autosomal recessive pattern. Furthermore, individuals with this phenotype can produce clinically significant antibodies.