Trophic Skin Ulceration of Leprosy: Skin and Serum Zinc Concentrations

Skin and serum zinc measurements have been made in patients with leprosy with and without trophic skin ulceration and in several other groups. Serum zinc concentrations were decreased in leprosy irrespective of the presence or absence of skin ulceration. Serum zinc concentrations in leprosy were also unrelated to smears positive for Mycobacterium leprae and to the clinical type of leprosy. Since a decrease of the serum zinc was also found in patients with dermatitis herpetiformis and pulmonary tuberculosis it seems likely that the decreased serum zinc in leprosy is a nonspecific metabolic consequence of chronic skin and internal disease. The mean skin zinc concentration in leprosy did not differ significantly from the corresponding value in control subjects, the lack of agreement between serum and skin concentrations being possibly related to the presence of nonexchangeable keratin-bound zinc in skin. Though the clinical significance of lowered serum zinc concentrations in leprosy is uncertain therapeutic trials of zinc treatment in leprosy with trophic skin ulceration seem justifiable.     

Safety and Efficacy Assessment of Two New Leprosy Skin Test Antigens: Randomized Double Blind Clinical Study

Background

New tools are required for the diagnosis of pre-symptomatic leprosy towards further reduction of disease burden and its associated reactions. To address this need, two new skin test antigens were developed to assess safety and efficacy in human trials.

Methods

A Phase I safety trial was first conducted in a non-endemic region for leprosy (U.S.A.). Healthy non-exposed subjects (n = 10) received three titrated doses (2.5 µg, 1.0 µg and 0.1 µg) of MLSA-LAM (n = 5) or MLCwA (n = 5) and control antigens [Rees MLSA (1.0 µg) and saline]. A randomized double blind Phase II safety and efficacy trial followed in an endemic region for leprosy (Nepal), but involved only the 1.0 µg (high dose) and 0.1 µg (low dose) of each antigen; Tuberculin PPD served as a control antigen. This Phase II safety and efficacy trial consisted of three Stages: Stage A and B studies were an expansion of Phase I involving 10 and 90 subjects respectively, and Stage C was then conducted in two parts (high dose and low dose), each enrolling 80 participants: 20 borderline lepromatous/lepromatous (BL/LL) leprosy patients, 20 borderline tuberculoid/tuberculoid (BT/TT) leprosy patients, 20 household contacts of leprosy patients (HC), and 20 tuberculosis (TB) patients. The primary outcome measure for the skin test was delayed type hypersensitivity induration.

Findings

In the small Phase I safety trial, reactions were primarily against the 2.5 µg dose of both antigens and Rees control antigen, which were then excluded from subsequent studies. In the Phase II, Stage A/B ramped-up safety study, 26% of subjects (13 of 50) showed induration against the high dose of each antigen, and 4% (2 of 50) reacted to the low dose of MLSA-LAM. Phase II, Stage C safety and initial efficacy trial showed that both antigens at the low dose exhibited low sensitivity at 20% and 25% in BT/TT leprosy patients, but high specificity at 100% and 95% compared to TB patients. The high dose of both antigens showed lower specificity (70% and 60%) and sensitivity (10% and 15%). BL/LL leprosy patients were anergic to the leprosy antigens.

Interpretation

MLSA-LAM and MLCwA at both high (1.0 µg) and low (0.1 µg) doses were found to be safe for use in humans without known exposure to leprosy and in target populations. At a sensitivity rate of 20–25% these antigens are not suitable as a skin test for the detection of the early stages of leprosy infection; however, the degree of specificity is impressive given the presence of cross-reactive antigens in these complex native M. leprae preparations.

Trial Registration

ClinicalTrails.gov {"type":"clinical-trial","attrs":{"text":"NCT01920750","term_id":"NCT01920750"}}NCT01920750 (Phase I), {"type":"clinical-trial","attrs":{"text":"NCT00128193","term_id":"NCT00128193"}}NCT00128193 (Phase II)     

Objective Analyses of Tessellated Fundi and Significant Correlation between Degree of Tessellation and Choroidal Thickness in Healthy Eyes

A tessellated fundus is a common characteristic of myopic eyes and is an important clinical marker for the development of retinochoroidal changes. However, the exact cause and significance of tessellated fundi have not been definitively determined. We determined the degree of tessellation in fundi objectively in normal, non-pathological myopic eyes, and correlated the degree of tessellation and the choroidal thickness (CT) and axial length (AL). This was a prospective observational cross sectional study. The eyes were classified subjectively into three groups based on the degree of tessellation observed ophthalmoscopically. Digital color fundus photographs were assessed for the degree of tessellation by ImageJ, an image processing program. Three tessellated fundus indices (TFIs) were calculated and were compared to the three subjectively-determined groups. The subfoveal and nasal CTs were measured in the optical coherence tomographic images. The correlations between the TFIs and the CT were calculated. Additionally, the correlation between the TFIs and the AL was calculated. One hundred right eyes of 100 healthy volunteers (mean age 25.8±3.9 years) were studied. Ophthalmoscopically, 57 eyes were placed in the non-tessellated group, 27 eyes into the weakly tessellated group, and 16 eyes into the strongly tessellated group. There was a significant correlation between the subjective classifications and the TFI values (P<0.05, Kruskal-Wallis test). All of the TFIs were significantly associated with the subfoveal and nasal CT (R = −0.20 to −0.24, P<0.05). The TFIs were not significantly correlated with the ALs. In conclusion, the significant correlation between the subjective and objective classifications of the degree of tessellation indicates that TFIs can be used to classify the degree of tessellation. The results indicate that the differences in the CT account for the degree of tessellation.     

Flat Mount Imaging of Mouse Skin and Its Application to the Analysis of Hair Follicle Patterning and Sensory Axon Morphology

Skin is a highly heterogeneous tissue. Intra-dermal structures include hair follicles, arrector pili muscles, epidermal specializations (such as Merkel cell clusters), sebaceous glands, nerves and nerve endings, and capillaries. The spatial arrangement of these structures is tightly controlled on a microscopic scale - as seen, for example, in the orderly arrangement of cell types within a single hair follicle - and on a macroscopic scale - as seen by the nearly identical orientations of thousands of hair follicles within a local region of skin. Visualizing these structures without physically sectioning the skin is possible because of the 2-dimensional geometry of this organ. In this protocol, we show that mouse skin can be dissected, fixed, permeabilized, stained, and clarified as an intact two dimensional object, a flat mount. The protocol allows for easy visualization of skin structures in their entirety through the full thickness of large areas of skin by optical sectioning and reconstruction. Images of these structures can also be integrated with information about position and orientation relative to the body axes.     

Allergic Skin Test Reactivity to Marijuana in the Southwest

In a general allergy consultation practice in Arizona and western New Mexico, 129 patients were tested for immediate hypersensitivity skin test reactivity to marijuana pollen and tobacco leaf, as well as to a battery of other antigens. In all, 90 patients were diagnosed as allergic (atopic) and, of these, 63 (70 percent) were found to be skin test reactive to marijuana pollen and 18 (20 percent) to tobacco leaf. The incidence of skin test reactivity to marijuana was not significantly different for persons living at low, middle or high elevations throughout the Southwest. Marijuana sensitivity occurred in patients who were, in general, also sensitive to a variety of other airborne plant pollens. There was no close correlation, however, between sensitivity to marijuana pollen and sensitivity to pollens from elm, mulberry, hop and stinging nettle, which are botanically related to marijuana. The data suggest that marijuana pollen may be a relatively common airborne pollen pollutant in the Southwest, allergic persons being sensitized through inhalation. If this is confirmed by further studies, then clinical investigation of marijuana hyposensitization (immunotherapy) may be warranted. This is in contrast to tobacco allergy for which simple avoidance is recommended.     

菜用大豆感官品质性状遗传变异及品质育种目标性状分析

以全国菜用大豆主产区154个品种为试验材料,考察感官品质性状综合位、6个一级、5个二级感官性状及7个有关理化性状的遗传变异,分析它们间的相关,从而概括出品质育种目标的主要性状。结果表明：感官性状综合品质位、6个一级、5个三级感官性状均存在牟它的遗传变异,其中二级感官性状的遗传变异度均大于一级感官性状。有关理化性状中,百英鲜直、百粗鲜直、可容性糖的遗传变异系数较大,遗传力较高,选择潜力较大;英长、英厚、英宽的遗传变异系数、遗传力中等,单英粒数的遗传变异系数、遗传力偏低。相关、偏相关和通径分材结果,粒英外观、熟食口味、生食口感对感官品质综合评定值直接效应显并较大;其中英厚、英长、百英鲜直对粒英外观的直接效应显,甜味及可溶性糖为影响蒸食品味的主要图素,硬度对生食口感直接负效应显。菜用大豆品质育种中,感官品质鉴定应在蒸食口味、生食口感、粒英外观、粒色、生样可剥性、熟食香味六个一级性状基础上综合评价,注重前三项性状的选择,它们可以结合用百英鲜重、英长、英厚、可溶性糖含量、鲜味、豆醒味、粘性、硬度等性状进行辅助选择。     

肾脏去神经化在心力衰竭治疗中的研究进展

生理情况下,心脏和肾脏在血流动力学和神经激素等调节中相互作用,对于循环系统的稳态维持起重要作用。但在充血性心力衰竭的病理情况下,心脏和肾脏之间存在明显的调节紊乱。首先,急性失代偿性心力衰竭的患者住院治疗的研究结果证明其有一定程度的肾脏失调。其次,慢性充血性心力衰竭时肾脏交感神经系统也起到重要作用:肾脏交感纤维活性增强可导致肾素的释放、钠水潴留、肾血流的降低、血管阻力增加、左心室重塑、左心功能失调等。众所周知,肾脏交感神经切除术可以减低血压和改善心脏功能,但是由于有创的手术方式限制了其应用。过去两年间,随着新的导管消融肾脏去神经化技术的日益完善,其有望成为治疗高血压病和心力衰竭的手段。在此,本文综述了心力衰竭时肾脏交感传入神经和传出神经的发病机理,对目前进行的经导管肾脏去神经化治疗慢性心力衰竭的基础及临床试验进行安全性及有效性评价。提示我们经导管肾脏去神经化有望成为心力衰竭治疗的新靶点。     

Medical History of Optic Chiasm Compression in Patients With Pituitary Insufficiency Affects Skin Temperature and Its Relation to Sleep

The hypothalamus is crucially involved in the circadian timing of the sleep-wake rhythm, yet also accommodates the most important thermoregulatory neuronal network. We have shown before that adults with pituitary insufficiency and history of chiasm compression due to a tumor with suprasellar extension fall asleep later and sleep shorter than those without such history and presumed hypothalamic involvement. To solidify the hypothesized link between vigilance and thermoregulation by the hypothalamus, we aimed to test the hypothesis that the presumed hypothalamic impairment in these patients also affects skin temperature and its association with sleep onset. In a case-control study of 50 patients (54.7?±?14.5 yrs of age, 30 males) with pituitary insufficiency, 33 of whom had a history of chiasm compression, ambulatory distal and proximal skin temperatures were assessed continuously for 24?h. Sleep parameters were assessed via questionnaire. Group differences in mean skin temperature, calculated over the wake and sleep periods separately, and group differences in the strength of association between pre-sleep skin temperature and sleep onset latency were compared. Results showed that patients with a medical history of chiasm compression had lower proximal skin temperature during the day (34.1°C?±?.7°C vs. 34.6°C?±?.7°C, p?=?.045). Additionally, the typical association between sleep onset latency and pre-sleep distal-to-proximal skin temperature gradient was absent in these patients (r?=??.01, p?=?.96), whereas it was unimpaired in those without chiasm compression (r?=??.61, p?=?.02). Thus, patients with history of chiasm compression show impaired skin temperature regulation in association with disturbed sleep. The findings support the hypothesis that a medical history of chiasm compression affects hypothalamic regulation of both vigilance and temperature, possibly by chronically affecting relevant nuclei, including the ventrolateral preoptic area and anterior hypothalamic preoptic area. (Corresponding Author: n.romeijn@nin.knaw.nl)     

The Challenge of Producing Skin Test Antigens with Minimal Resources Suitable for Human Application against a Neglected Tropical Disease; Leprosy

True incidence of leprosy and its impact on transmission will not be understood until a tool is available to measure pre-symptomatic infection. Diagnosis of leprosy disease is currently based on clinical symptoms, which on average take 3–10 years to manifest. The fact that incidence, as defined by new case detection, equates with prevalence, i.e., registered cases, suggests that the cycle of transmission has not been fully intercepted by implementation of multiple drug therapy. This is supported by a high incidence of childhood leprosy. Epidemiological screening for pre-symptomatic leprosy in large endemic populations is required to facilitate targeted chemoprophylactic interventions. Such a test must be sensitive, specific, simple to administer, cost-effective, and easy to interpret. The intradermal skin test method that measures cell-mediated immunity was explored as the best option. Prior knowledge on skin testing of healthy subjects and leprosy patients with whole or partially fractionated Mycobacterium leprae bacilli, such as Lepromin or the Rees'' or Convit'' antigens, has established an acceptable safety and potency profile of these antigens. These data, along with immunoreactivity data, laid the foundation for two new leprosy skin test antigens, MLSA-LAM (M. leprae soluble antigen devoid of mycobacterial lipoglycans, primarily lipoarabinomannan) and MLCwA (M. leprae cell wall antigens). In the absence of commercial interest, the challenge was to develop these antigens under current good manufacturing practices in an acceptable local pilot facility and submit an Investigational New Drug to the Food and Drug Administration to allow a first-in-human phase I clinical trial.     

感觉神经损伤性盐敏感性高血压大鼠心、肾AT1R的表达

目的对感觉神经损伤性盐敏感性高血压大鼠的心肌、肾脏组织中的血管紧张素Ⅱ1型受体（AT1R）在mRNA和受体水平的表达进行检测,探讨AT1R与盐敏感性高血压的关系。方法用乳鼠皮下注射辣椒辣素法建立模型。哺乳期后,大鼠被随机分成4组：对照＋正常盐饮食组（CON-NS）;对照＋高盐饮食组（CON-HS）;辣椒辣素＋正常盐饮食组（CAP-NS）;辣椒辣素＋高盐饮食组（CAP-HS）。至7周龄（分组饲养后第4周）处死大鼠,免疫组织化学方法和反转录-聚合酶链式反应（RT-PCR）分别检测大鼠心肌和肾脏AT1R蛋白,以及AT1 R mRNA的表达。结果①Wistar大鼠在给予不同程度的感觉神经损伤和饲料干预后,各组大鼠尾部收缩压均有明显增加,最终CAP-HS组的尾收缩压显著高于其他三组（P〈0.01）。②免疫组织化学结果显示,CAP-HS组组织有显著的AT1R蛋白表达（P〈0.01）;CON-HS组肾脏、心肌组织中AT1R蛋白表达高于CON-NS组（P〈0.05）。③RT-PCR检测基因表达,与对照组CON-NS相比,实验组CAP-HS的AT1R mRNA表达显著升高（P〈0.01）;CON-HS组肾脏、心肌组织中AT1 R mRNA表达有显著性（P〈0.05）。结论感觉神经损伤性盐敏感性高血压大鼠心、肾AT1R表达升高,AT1R表达水平的差异可能与盐敏感性高血压的形成有关。     

血清HBP、uNAG及Lp-PLA2在糖尿病酮症酸中毒患者中的表达及与病情程度的相关性分析

摘要 目的：探讨血清肝素结合蛋白（HBP）、N-乙酰-β-D-氨基葡萄糖苷酶（uNAG）及脂蛋白相关磷脂酶A2（Lp-PLA2）在糖尿病酮症酸中毒患者中的表达及与病情程度的相关性。方法：选择2018年3月至2020年3月于我院进行治疗的78例糖尿病酮症酸中毒患者进行研究,设为病例组,并选择我院同期治疗的单纯糖尿病患者70例作为对照组,分析血清HBP、uNAG及Lp-PLA2水平变化情况及与病情程度的相关性及其预测价值。结果：病例组血清HBP、uNAG及Lp-PLA2水平显著高于对照组,差异显著（P＜0.05）;轻度组血清HBP、uNAG及Lp-PLA2显著低于中度组、重度组患者,中度组HBP、uNAG及Lp-PLA2显著低于重度组患者,差异显著（P＜0.05）;相关性分析结果中显示,血清HBP、uNAG及Lp-PLA2均和病情程度之间呈正相关（P＜0.05）;ROC结果显示,血清HBP预测糖尿病酮症酸中毒的AUC为0.804,灵敏度为82.56%,特异度为86.32%,截断值为59.92 ng/mL;uNAG预测糖尿病酮症酸中毒的AUC为0.886,灵敏度为83.48%,特异度为87.95%,截断值为12.53 IU/L;血清Lp-PLA2预测糖尿病酮症酸中毒的AUC为0.977,灵敏度为88.69%,特异度为89.97%,截断值为194.96 ng/L,（P＜0.05）。结论：血清HBP、uNAG及Lp-PLA2在糖尿病酮症酸中毒患者中表达异常,与病情程度之间关系密切,对于病情控制具有重要临床意义。     

Antibodies to Myelin P0 and Ceramide Perpetuate Neuropathy in Long Standing Treated Leprosy Patients

Anti neural antibodies are known to play a role in the immunopathogenesis of nerve damage in leprosy and HIV/AIDS. Myelin Protein zero (P0) and ceramide are two nerve components which maintain the integrity of the peripheral nerve. The present study was undertaken to identify antibodies to myelin P0 and ceramide in the sera of treated leprosy patients, HIV positive individuals and healthy subjects using enzyme linked immunosorbant assay (ELISA). The results revealed that treated leprosy patients continue to have significantly elevated myelin P0 and ceramide antibody levels as compared to healthy subjects (P??0.05) suggesting that these antibodies do not play a role in early HIV infection.     

哈萨克族原发性高血压患者血浆CGRP水平及其相关性研究

目的:探讨血浆降钙素基因相关肽(CGRP)水平与新疆哈萨克族(哈族)原发性高血压病患者血压、血脂、血糖、肥胖等的相关性。方法:选取新疆哈族原发性高血压患者52例为观察组,哈族健康对照组48例,测量血压(BP)、身高、体重、腰围(WC)、臀围(HC),抽取空腹静脉血测定血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),计算体重指数(BMI)腰臀比(WHR)。结果:①原发性高血压组血浆CGRP水平明显低于对照组,差异有统计学意义(p<0.01);②原发性高血压组血浆CGRP水平与SBP、LDL-C和TG呈显著负相关(p<0.01);对照组血浆CGRP水平与SBP和LDL-C呈显著负相关(p<0.01)。结论:哈族原发性高血压患者血浆CGRP水平与血压、血脂存在相关性。     

Neuron Specific Enolase and C-reactive Protein Levels in Stroke and Its Subtypes: Correlation with Degree of Disability

Stroke is an emergency which threatens life and third leading cause of death and long term disability in developed countries. The use of biomarkers in diagnosing stroke and assessing prognosis is an emerging and rapidly evolving field. The study aimed to investigate the predictive value of biochemical marker of brain damage neuron-specific enolase (NSE) and systemic inflammatory marker C-reactive protein (CRP) with respect to degree of disability at the time of admission and short term in stroke patients. We investigated 120 patients with cerebrovascular stroke who were admitted within 72 h of onset of stroke in the Department of Neurology at Sri Aurobindo Institute of Medical Sciences, Indore, India. NSE and CRP were analyzed by solid enzyme linked immunosorbent assay using analyzer and micro plate reader from Biorad 680. In all patients, the neurological status was evaluated by a standardized neurological examination and the National Institutes of Health Stroke Scale on admission and on day 7. Serum NSE and CRP concentration were found significantly increased in acute stroke cases as compared to control in present study (<0.05 and <0.001 respectively). The maximum serum NSE and CRP levels within 72 h of admission were significantly higher in patients with greater degree of disability at the time of admission. Both biomarkers were found significantly correlated with neurological disability and short term outcome. Our study showed that serum biomarkers NSE and CRP have high predictive value for determining severity and early neurobehavioral outcome after acute stroke.     

Comparative Study of 1,064-nm Laser-Induced Skin Burn and Thermal Skin Burn

Infrared lasers are widely used in medicine, industry, and other fields. While science, medicine, and the society in general have benefited from the many practical uses of lasers, they also have inherent safety issues. Although several procedures have been put forward to protect the skin from non-specific laser-induced damage, individuals receiving laser therapy or researchers who use laser are still at risk for skin damage. This study aims to understand the interaction between laser and the skin, and to investigate the differences between the skin damage caused by 1,064-nm laser and common thermal burns. Skin lesions on Wistar rats were induced by a 1,064-nm CW laser at a maximum output of 40 W and by a copper brass bar attached to an HQ soldering iron. Histological sections of the lesions and the process of wound healing were evaluated. The widths of the epidermal necrosis and dermal denaturalization of each lesion were measured. To observe wound healing, the epithelial gap and wound gap were measured. Masson’s trichrome and picrosirius red staining were also used to assess lesions and wound healing. The thermal damage induced by laser intensified significantly in both horizontal dimension and in vertical depth with increased duration of irradiation. Ten days after wounding, the dermal injuries induced by laser were more severe. Compared with the laser-induced skin damage, the skin burn induced by an HQ soldering iron did not show a similar development or increased in severity with the passage of time. The results of this study showed the pattern of skin damage induced by laser irradiation and a heated brass bar. This study also highlighted the difference between laser irradiation and thermal burn in terms of skin damage and wound healing, and offers insight for further treatment.     

感觉神经损伤性盐敏感性高血压大鼠心、肾ACE和ACE2的表达

目的研究肾素-血管紧张素系统（RAS）基因血管紧张素转换酶（ACE）和血管紧张素转换酶2（ACE2）在感觉神经损伤性盐敏感性高血压大鼠心肌和肾脏中的表达情况,探讨ACE、ACE2在盐敏感性高血压发生发展中的作用。方法用乳鼠皮下注射辣椒辣素法建立模型。哺乳期后,大鼠被随机分成4组：对照＋正常盐饮食组（CON-NS）、对照＋高盐饮食组（CON-HS）、辣椒辣素＋正常盐饮食组（CAP-NS）、辣椒辣素＋高盐饮食组（CAP-HS）。四组大鼠分别接受4周不同的处理。至7周龄（分组饲养后第4周）处死大鼠,免疫组化检测大鼠心肌和肾脏ACE和ACE2蛋白的表达,反转录-聚合酶链式反应（RT-PCR）检测大鼠心肌和肾脏ACE和ACE2mRNA的表达。结果①至7周龄（分组饲养后第4周）各组动物体重差异无显著性（P〉0.05）。②各组动物在分组时（0周）鼠尾收缩压差异无显著性（P=0.583）,至7周龄（分组饲养后第4周）,CAP-HS组鼠尾收缩压明显高于其它三组（P〈0.01）。③心肌和肾脏ACE蛋白表达均升高。心肌组织,CAP-HS组与CON-NS比较,P〈0.01,与CON-HS和CAP-NS比较,P〈0.05;肾脏组织,CAP-HS组与其它三组比较,P〈0.01。④心肌和肾脏ACE2蛋白表达均降低。心肌和肾脏组织,CAP-HS组与CON-NS和CAP-NS比较,P〈0.01,与CON-HS比较,P〈0.05。⑤心肌和肾脏ACE mRNA表达均升高。心肌组织,CAP-HS组与CON-NS比较,P〈0.01,与CON-HS和CAP-NS比较,P〈0.05;肾脏组织,CAP-HS组与其它三组比较,P〈0.01。⑥心肌和肾脏ACE2 mRNA表达均降低。心肌和肾脏组织,CAP-HS组与CON-NS和CAP-NS比较,P〈0.01,与CON-HS比较,P〈0.05。结论感觉神经损伤性盐敏感性高血压大鼠心、肾ACE表达升高的同时有ACE2表达的降低,ACE和ACE2表达水平的差异可能与盐敏感性高血压的形成有关。