Intermediate-term toxicity of repeated orally administered doses of the anti-malarial β-artemether in dogs

The artemisinin derivative beta-artemether, an anti-malarial, was evaluated for its toxicity and tolerability in a 2-week, multiple-dose study in dogs. Eight beagle dogs (4 females, 4 males) were given beta-artemether by oral gavage 3 times daily at 45 mg/kg/dosing (a total daily dose-level of 135 mg/kg) for 2 weeks. This beta-artemether dose regime was well tolerated. Body weight changes were normal although feed consumption during the treatment period reduced compared to that of the pre-trial period. Clinical signs were transient spells of soft to liquid feces. On completion of the treatment period, the animals were sacrificed and submitted to a full macroscopic post-mortem examination. Designated organs were weighed and a complete light microscopic examination was performed on 43 selected tissues from 1 animal per sex, and on the liver, kidneys, thymus, mandibular lymph nodes and lungs of the three other animals per sex. Major findings were high liver weight and histopathologic findings of slight diffuse hepatocellular hypertrophy and distal tubular dilatation, together with flattened epithelium, in the kidneys. With the dose regime used in this trial beta-artemether produced no clinical or apparent histopathological signs of neurotoxicity in dogs.     

Lens junctional protein: analyzing MP26 with monoclonal antibodies

Specific antibodies are versatile tools for analyzing cell surface proteins. This study involves the characterization of monoclonal antibodies which are specific for the junctional protein found in the lens fiber cell. This protein can be expected to include regions on the external membrane surface for junction formation, others on the cytoplasmic surface for regulation of junctional properties and, if cell-cell channels are indeed involved, transmembrane domains forming the hydrophilic connection between adjacent cytoplasms. Antibodies to these various regions would provide for an experimental analysis of the junctional protein, e.g., the identification of "active sites" for junction formation. Three monoclonal antibodies specific for the lens junctional protein in the chicken are described here. The first, termed B2, also recognizes the bovine junctional protein, MP26 (5). We have characterized the submolecular specificity of B2 and have found that it binds approximately ten amino acid residues from the C-terminus of MP26. In isolated lens junction preparations, B2 binds to the cytoplasmic surfaces of the lens junctions (both 12 nm and 16 nm thick forms). Thus, we consider MP26 a component of the lens junction. Monoclonal A4, the second antibody considered in detail here, was produced by immunization with lens membranes after treatment with low pH. We have found that lens junctional membranes are separated, or "split," by treatment at pH 2.5-3.0. It appears that A4 binds to the external surface of the junctional membrane; EM studies to confirm this are in progress. In order to map the A4 binding site within the chicken junctional protein and to explore the arrangement of this protein within the membrane, a number of procedures were used to generate fragments of MP26. These included reactions with N-chlorosuccinimide and proteases after acid treatment. Antibody binding to fragments was evaluated with immunotransfer ("Western") procedures. These studies mapped the A4 binding site to the center of the molecule and suggested that MP26 projected externally from the membrane at two different points. These results are consistent with a recent model, based on sequence data (6), for the arrangement of MP26 within the bovine lens membrane.     

医学生对标准化病人应用于临床医学专业执业医师技能考核的认知及满意度评价研究

目的 了解医学生对标准化病人（SP）应用于临床医学专业执业医师技能考核的认知及满意度评价情况,为加强医学人才培养、推动安徽省医学教育改革提供参考依据。方法 2021年5月以问卷调查的方式收集546名参加安徽省某高校2021年临床执业医师技能考核的学生对SP认知情况及满意度评价情况,同时开展临床执业医师技能考核,收集学生考核通过情况。采用χ2检验对SP应用于临床技能考核的认知情况及满意度评价情况进行分析。结果 546名医学生的临床执业医师技能考核合格率为84.80%。调查对象知晓SP教学或考核的比例为88.64%,接受过SP教学或考核的比例为17.77%。调查对象对SP临床技能考核的满意率为89.38%,五个层面的满意率从高到低依次为剧本内容（94.32%）、场所设施（93.77%）、时间安排（89.93%）、试题难度（88.64%）、角色表现（85.35%）。不同学制、不同SP临床技能考核通过情况的调查对象在SP应用于临床专业执业医师技能考核认知情况及满意度评价方面存在差异（P<0.05）。结论 SP临床技能考核的应用情况和满意度评价情况需进一步提升,建议卫生教育主管部门明确使用...     

Adrenergic,purinergic, and endothelial mediators and modulators of norepinephrine-induced mesenteric autoregulatory escape

We evaluated the effects of potential factors in autoregulatory escape from norepinephrine-induced vasoconstriction in rat anterior mesenteric artery. We determined mesenteric artery blood flow velocity with a pulsed Doppler, sonic flowmeter, and systemic arterial blood pressure with a transducer. A 4-min norepinephrine infusion (0.125–1.0 × 10^–8 M/min) intravenously evoked a dose-dependent, initial vasoconstriction that was followed by rapid escape of blood flow toward or above the control value during sustained norepinephrine administration. Neonatal capsaicin treatment enhanced vasoconstrictor responses to norepinephrine but failed to affect escape parameters. Propranolol decreased norepinephrine-induced escape dose dependently. Adenosine deaminase attenuated escape, and the combination of this enzyme plus propranolol nearly abolished escape from norepinephrine-induced vasoconstriction. Methylene blue also diminished autoregulatory escape. These findings suggest that norepinephrine-induced autoregulatory escape involves simultaneous -adrenoceptor, purinergic, and endothelial mediation. Norepinephrine-evoked mesenteric vasoconstriction appears to involve predominantly ₂-adrenoceptors and is modulated by peptidergic sensory nerves and adenosine.NIH grant number supporting these studies: USPHS # DK37050.     

Parlodel treatment of patients with pathospermia

The response to bromoergocryptine (Parlodel, Sandoz) was examined in 42 pathospermic patients. The authors conclude that Parlodel did not influence the spermiogram considerably. Serum prolactin levels were lowered significantly, while the FSH, LH, testosterone, 17--hydroxyprogesterone and 17--oestradiol concentrations did not change. Improvement was reported in potentia coeundi in one third of the patients.Supported by the Scientific Research Council, Ministry of Health, Hungary (4-29-0302-01-2/S).     

Model of Moderate Hyperhomocisteinemia Associated with Mechanical Injury: Dynamics of Morphometric Parameters of Microcirculatory Vessels

Bulletin of Experimental Biology and Medicine - A model of moderate hyperhomocysteinemia associated with mechanical injury of the musculoskeletal system was developed and experimentally...     

Further investigations on antithrombin III in the plasmas of patients with the abnormality of antithrombin III Budapest.

Antithrombin III (AT-III) was studied in a thrombophilic family with an abnormal AT-III molecule (antithrombin III Budapest) using a modified crossed immunoelectrophoresis technique, gel filtration, 'rocket' immunoelectrophoresis and a heparin cofactor assay. When agarose was applied in the first phase of the crossed immunoelectrophoresis, the normal and the pathological AT-III revealed identical electrophoretic mobility. However, when heparin was mixed with agarose in the first phase of electrophoresis, the propositus' plasma displayed a different AT-III pattern from normal plasma. His plasma contained the first component of the normal plasma (Immune Antithrombin III1, IAT-III) in a concentration of only 5% of normal, and a protein in high concentration which although immunoreactive to AT-III antisera, had an electrophoretic mobility similar (but not identical to that of IAT-III2. This abnormal protein had no heparin cofactor activity and a molecular size greater than normal plasma AT-III. Unlike AT-III, the addition of heparin did not change the molecular size of the pathogic AT-III molecule significantly. The abnormal protein was present in lower concentrations in the patient's children and at the time of study they had no clinical or laboratory evidence of intravascular coagulation.