Physiology of Intestinal Absorption and Secretion

Virtually all nutrients from the diet are absorbed into blood across the highly polarized epithelial cell layer forming the small and large intestinal mucosa. Anatomical, histological, and functional specializations along the gastrointestinal tract are responsible for the effective and regulated nutrient transport via both passive and active mechanisms. In this chapter, we summarize the current state of knowledge regarding the mechanism of intestinal absorption of key nutrients such as sodium, anions (chloride, sulfate, oxalate), carbohydrates, amino acids and peptides, lipids, lipid- and water-soluble vitamins, as well as the major minerals and micronutrients. This outline, including the molecular identity, specificity, and coordinated activities of key transport proteins and genes involved, serves as the background for the following chapters focused on the pathophysiology of acquired and congenital intestinal malabsorption, as well as clinical tools to test and treat malabsorptive symptoms.     

Efficacy of Oral Zinc Sulfate Supplementation on Clearance of Cervical Human Papillomavirus (HPV); A Randomized Controlled Clinical Trial

Aim: Human Papillomavirus is one of the most crucial infectious disease in gynecology disease. To assess the efficacy of supplemental zinc treatment in clearance of HPV infection. Methods: Eighty zinc-sufficient women between 21-55 years, with positive HPV DNA testing, and abnormal cervical cytology in Pap test (ASCUS or LISL) were randomly divided to case (n=40) and control group (n=40). Case group received oral tablets of zinc sulfate twice a day for 3 months while control group received no placebo. During follow-up patients underwent repeat HPV DNA test and PAP test and were evaluated for clearance/persistence of HPV infection and regression/progression in the lesion grading. Results: As far as demographics, serum zinc levels and the relevant risk factors for persistence of HPV were concerned, there was no significant difference between two groups, except for the frequency distribution of HR-HPV which was significantly higher in case  group. Zinc treatment for 3 months reduced the risk of persistence of HPV infection and progression from baseline cytology (OR = 0.130) (CI 95% 0.04-0.381; p <0.001) and 0.301 (95% CI 0.777-0.116; p = 0.012), respectively. Age, initial cytology, HPV type, and contraceptive method were not related to persistence of HPV. Serum zinc levels increased in the casr group as a result of oral zinc consumption for 3-month period, though without any statistical significance (p = 0.407). Conclusion: The results of the following study suggested that oral intake of zinc sulfate supplement for 3 months increases the rates of HPV clearance and resolution of pre-existing cervical lesion.     

普米克令舒联合硫酸镁治疗新生儿胎粪吸入综合征的临床研究

目的 探讨普米克令舒联合硫酸镁治疗新生儿胎粪吸入综合征的临床效果.方法 纳入广东省茂名市人民医院2010年4月～2014年4月收治的新生儿胎粪吸入综合征患儿123例.将其分为观察组(n=43)、硫酸镁组(n=40)、普米克令舒组(n=40).观察组采用普米克令舒联合硫酸镁治疗,硫酸镁组给予硫酸镁治疗,普米克令舒组给予普米克令舒治疗.对比分析三组患儿治疗前后动脉血气指标水平、肺动脉收缩压(PASP)、氧暴露时间、住院时间及疗效.结果 观察组治疗后12、24 hpH与同期硫酸镁组和普米克令舒组比较差异无统计学意义(P＞0.05),血氧分压明显高于硫酸镁组和普米克令舒组,动脉血二氧化碳分压明显低于硫酸镁组和普米克令舒组,差异均有统计学意义(P＜0.05);观察组治疗后12、24 h PASP水平明显低于硫酸镁组和普米克令舒组,差异有统计学意义(P＜0.05);观察组氧暴露时间[(5.49±0.85)d]和住院时间[(12.95±2.31)d]均显著短于硫酸镁组[(7.93±1.12)、(16.41±2.57)d]及普米克令舒组[(7.78±1.05)、(16.23±2.41)d],差异有统计学意义(P＜ 0.05);观察组总有效率(86.05％)显著高于硫酸镁组(65.00％)和普米克令舒组(62.50％),差异有统计学意义(P＜0.05).结论 普米克令舒联合硫酸镁治疗新生儿胎粪吸入综合征临床效果显著,具有重要的临床研究价值.     

Oral Zinc Sulfate as Adjuvant Treatment in Children With Nephrolithiasis: a Randomized,Double-Blind,Placebo-Controlled Clinical Trial

Background:

Nephrolithiasis in children is associated with a high rate of complications and recurrence.

Objectives:

Since some evidences reported that zinc has an important place amongst inhibitors of crystallization and crystal growth, we decided to assess the effectiveness of oral zinc sulfate as adjuvant treatment in children with nephrolithiasis.

Patients and Methods:

This was a randomized, double-blind, placebo-controlled clinical trial. 102 children in the age range 1 month to 11 years with first nephrolithiasis were recruited. Patients were randomly divided into two equal groups (intervention and control groups). Intervention group received conservative measures for stones and 1 mg/kg/day (maximum 20 mg/day) oral zinc sulfate syrup for 3 months. Control group received placebo in addition to conservative measures, also for 3 months. Patients were followed up by ultrasonography for 9 months, in 5 steps (at the end of 1st, 2nd, 3rd, 6th and 9th month after treatment) assessing size and number of stones in the kidneys.

Results:

Only at the end of the first month, the average number (intervention: 1.15 ± 3.78, control: 1.3 ± 2.84) (P = 0.001) and size (cm) (intervention: 0.51 ± 1.76, control: 0.62 ± 1.39) (P = 0.001) of stones was significantly lower in the intervention group, and in other points there was no significant therapeutic efficacy in oral zinc adjuvant treatment compared to conservative treatment alone. Also, during the 9-month follow-up, the number and size of stones in both groups decreased significantly (both: P < 0.0001) in a way that the decrease in the intervention group showed no difference with the control group.

Conclusions:

Adjuvant treatment with zinc is not more effective than consecutive treatment in children with nephrolithiasis. However, further studies are recommended due to the lack of clinical evidence in this field.     

The development and validation of methods for evaluating the immune system in preweaning piglets

The preweaning piglet has been found to be a valuable research model for testing ingredients used in infant formula. As part of the safety assessment, the neonates' immune system is an important component that has to be evaluated. In this study three concurrent strategies were developed to assess immune system status. The methods included (1) immunophenotying to assess circulating innate immune cell populations, (2) monitoring of circulating cytokines, particularly in response to a positive control agent, and (3) monitoring of localized gastrointestinal tissue cytokines using immunohistochemistry (IHC), particularly in response to a positive control agent. All assays were validated using white papers and regulatory guidance within a GLP environment. To validate the assays precision, accuracy and sample stability were evaluated as needed using a fit for purpose approach. In addition animals were treated with proinflammtory substances to detect a positive versus negative signal. In conclusion, these three methods were confirmed to be robust assays to evaluate the immune system and GIT-specific immune responses of preweaning piglets.     

Identification of the major allergenic proteins from silkworm moth (Bombyx mori) involved in respiratory allergic diseases

Introduction and ObjectivesMoths are a significant source of indoor and outdoor aeroallergens. High prevalence of IgE-mediated sensitization was demonstrated in a group of patients with allergic respiratory diseases. There are no studies on adult stage of these moth species allergens involved in allergic respiratory reactions - the aim of this study.Material and Methods36 participants were included in an experimental study, submitted to skin prick test with Bombyx mori wing extract and six other common allergens, as well as Western blot analysis with incubated nitrocellulose membrane impregnated with silkworm moth extract and human IgE-antibody. The participants were divided into 3 groups: 1) 21 allergic patients whose skin prick test was positive to Bombyx mori wing extract, 2) eight allergic patients whose skin prick test was positive to mite and negative to Bombyx mori extract 3) seven negative non-allergic subjects.ResultsAmong the 21 participants from group 1, 19 serum samples reacted to Bombyx mori extract by Western blot. All of them reacted to a protein at 80 kDa and five other proteins (66, 50, 45, 37 and 30 kDa) were identified in more than 50% of the individuals tested, considered as major allergenic proteins. Sera from seven out of eight patients sensitized to house dust mite demonstrated IgE-reactivity to Bombyx mori extract by Western blot analysis. Serum samples from healthy participants did not react at all.ConclusionSix major reactive proteins by immunoblot analysis from moth’s wings sensitized patients can be potential allergens. The one at 80 kDa is the major protein, seen in all IgE-reactive patients from group 1 and in none from group 2, yet to be identified. Future studies should be conducted to better characterize these proteins.     

哮喘宁颗粒联合复方硫酸沙丁胺醇治疗支气管哮喘慢性持续期的临床研究

目的 探讨哮喘宁颗粒联合硫酸沙丁胺醇气雾剂治疗支气管哮喘慢性持续期患者的临床疗效。方法 选取2017年9月—2019年11月郑州大学第五附属医院收治的98例支气管哮喘慢性持续期患者为研究对象,根据抽签法将患者分为对照组（49例）和治疗组（49例）。对照组吸入复方硫酸沙丁胺醇气雾剂,早晚各1吸。治疗组在对照组治疗的基础上口服哮喘宁颗粒,25 g/次,2次/d。两组均治疗12周。观察两组的临床疗效,比较两组的肺功能、血清炎性因子。结果 治疗后,治疗组的总有效率为93.88%,高于对照组的75.51%（P<0.05）。治疗后,两组用力肺活量（FVC）、第一秒用力呼气量（FEV₁）、最大呼气峰流速（PEF）均升高（P<0.05）,且治疗组肺功能高于对照组（P<0.05）。治疗后,两组干扰素-γ（IFN-γ）、白细胞介素-4（IL-4）、白细胞介素-17（IL-17）水平降低,白细胞介素-10（IL-10）水平升高（P<0.05）,且治疗组IFN-γ、IL-4、IL-17水平低于对照组,IL-10水平高于对照组（P<0.05）。结论 哮喘宁颗粒联合硫酸沙丁胺醇气雾剂治疗支气管哮喘慢性持续期具有较好的疗效,可明显改善肺功能,减轻炎症反应,且安全性较好。     

Effect of Decorin and Dermatan Sulfate on the Mechanical Properties of a Neocartilage

Decorin is known to influence the size of collagen fibrils in ligaments and tendons and it has been hypothesized to provide a structural link between collagen fibrils in connective tissues, including cartilage. Coincidently, mechanical properties of skin, ligament, and tendons are altered in decorin knockout mice, suggesting it may influence the structural properties of tissue or tissue matrix organization. To further examine the role of decorin in the extracellular matrix development and subsequent material properties of cartilage, tissue (neocartilage) was grown in a 3D culture model using a pure population of genetically modified chondrocytes stably overexpressing decorin (DCN) or decorin lacking dermatan sulfate (MDCN). An empty vector (CON) served as a virus control. Following generation of the cartilage-like tissues, mechanical properties in tension and compression, collagen fibril diameter, matrix organization, and biochemistry of the tissue were determined. There were no differences between CON and DCN tissues in any parameter measured. In contrast, tissue generated in MDCN cultures was thinner, had higher collagen density, and higher elastic moduli as compared to both CON and DCN tissues. Considering there was no difference in stiffness between CON and DCN tissues, the notion that decorin contributes to the mechanical properties via load transfer was refuted in this model. However, contrasts in the mechanical properties of the MDCN tissue suggest that the dermatan sulfate chains on decorin influences the organization/maturation and resultant mechanical properties of the matrix by as an yet-unidentified regulatory mechanism.     

In vivo Heparan Sulfate Treatment Alters the Immune Response of Normal and LLC-Bearing Mice

Despite the large amount of research dedicated to the understanding and treatment of tumor growth, the majority of cancers continue to lack effective therapeutic options. As in the case of most solid tumors, growth requires evasion of the host immune system. Our previous work using the Lewis Lung Carcinoma (LLC) model of tumor bearing (TB)-mice has shown several tumor-induced immune suppressing effects to be present. These effects include a decreased T-cell proliferative response to Con A and altered cytokine secretion patterns that favor neither a Th1 nor a Th2 response. To address these immune alterations, immune modulating approaches have been a central area of study. Of the many potential immune modulating compounds, we believe promising therapeutic potential lies in the heparin family. Heparan sulfate (HS), in particular, has been shown to increase T-cell proliferative response in non TB-mouse splenocytes as well as promotion of a beneficial Th1 response. In this paper, we studied the potential of HS to decrease tumor burden via in vivo treatment of TB-mice. Results showed both normal and TB-mice splenocytes had a dose response change in proliferation as a result of HS treatment. Furthermore, splenocytes from HS treated TB-mice showed a potentially beneficial decrease in basal level proliferation. On gross examination, HS treatment produced a decrease in tumor surface necrosis with a visible (2 ± 1.8%) surface necrotic area in treated mice as opposed to a (43 ± 16%) surface necrotic area in untreated mice. HS treatment decreased TB-mice splenomegaly when comparing mice spleen weights in treated (0.3 ± 0.05 g) vs. untreated (0.14 ± 0.02 g) groups. These results show a potential role of HS as an immune modulating agent with antitumor properties.