Metabolism and pharmacokinetics studies of allyl methyl disulfide in rats

1. Allyl methyl disulfide (AMDS) is one of the main compounds in garlic, whereas its metabolism has not been studied yet.

2. In this work, we first identified the metabolites of AMDS in rat erythrocytes and rats using GC–MS. The transformation mechanism study among different metabolites was then conducted. The apparent kinetics of AMDS in rat erythrocytes and pharmacokinetics of AMDS by oral administration in rats were also studied.

3. The metabolic pathway study showed that AMDS was mainly metabolized in rats to allyl methyl sulfoxide (AMSO) and allyl methyl sulfone (AMSO₂) through mechanisms of reduction, methylation and oxidation. The transformation mechanism study indicated that AMDS was firstly reduced to allyl mercaptan (AM) in rat erythrocytes, and then methylated to allyl methyl sulfide (AMS) by S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and finally oxidized to AMSO and AMSO₂ by liver microsomes. The half-life of AMDS in rat erythrocytes was 6.285?±?0.014?min while the half-lives of its active metabolites AMSO and AMSO₂ in vivo were 18.17 and 17.50?h, respectively. Also, the large AUCs of the two active metabolites were observed, indicating potential applications of AMDS for certain pharmacological effects.     

滋肾化石汤辅助双镜联合术治疗复杂性肾结石的疗效及对红细胞免疫功能的影响

目的 评价滋肾化石汤辅助双镜联合术治疗复杂性肾结石的疗效及对患者红细胞免疫功能的影响。方法 该研究为前瞻性随机对照试验,选取2018年10月—2021年4月就诊于唐山市工人医院的108例复杂性肾结石患者。按随机数表法分组将患者分为对照组和实验组,每组54例。对照组接受经皮肾镜联合输尿管软镜碎石取石术,实验组实施经皮肾镜联合输尿管软镜碎石取石术+滋肾化石汤治疗。对比两组疗效、一期手术结石清除率、肾损伤因子、红细胞免疫功能、炎症应激反应、并发症。结果 实验组总有效率、一期手术结石清除率较对照组高（P <0.05）。两组术前血清人肾损伤分子1（KIM-1）、中性粒细胞明胶酶相关载脂蛋白（NGAL）、尿素氮（BUN）及胱抑素C（Cys-C）水平比较,差异无统计学意义（P >0.05）,实验组术后7 d血清KIM-1、NGAL、BUN及Cys-C水平较对照组低（P <0.05）。两组术前血清红细胞C3b受体花环率（C3bRR）、免疫复合物受体花环率（ICRRR）、肿瘤红细胞花环率（TER）及红细胞免疫复合物花环率（RBC-ICR）水平比较,差异无统计学意义（P >0.05）,实验组术后7 d血清C3bRR、ICRRR、TER及RBC-ICR水平较对照组高（P <0.05）。两组术前血清白细胞介素-1β（IL-1β）、高敏C反应蛋白（hs-CRP）、血管紧张素Ⅰ（AngⅠ）及血管紧张素Ⅱ（AngⅡ）水平比较,差异无统计学意义（P >0.05）。实验组术后7 d血清血清IL-1β、hs-CRP、AngⅠ及AngⅡ水平较对照组低（P <0.05）。两组并发症发生率比较,差异无统计学意义（P >0.05）。结论 复杂性肾结石患者接受滋肾化石汤辅助双镜联合术的效果确切,可提升一期手术结石清除率,减轻肾损伤,改善红细胞免疫功能,降低炎性应激反应。     

Human carbonic anhydrase I concentration in erythrocytes during pregnancy and the menstrual cycle

Carbonic anhydrase I (HCAI) concentrations were measured in erythrocytes (RBC) taken from nine women at intervals throughout their pregnancies and from thirteen normal women during the menstrual cycle. No significant changes in RBC HCAI concentrations were found in any instance. Small changes which were found in RBC HCAI concentrations were within experimental error and did not correlate with any other measured parameter. Changes in RBC HCAI concentrations in six men over a four-week period were of similar order to that found in the thirteen normal women over a similar length of time.     

干化学法与沉渣镜检法对比检测尿中红细胞和白细胞

目的探讨迪瑞H-300尿液分析仪干化学法与尿沉渣镜法检测红细胞和白细胞的一致性。方法对3678例尿液分析仪干化学测定全部为阴性、619例测定为隐血±至＋＋同时白细胞阴性的尿液标本做尿沉渣镜检。结果3678例阴性标本尿沉渣镜检检出白细胞每高倍视野5～30个以上206例，假阴性率占5．6％；红细胞每高倍视野3～15个115例，假阴性率为3．1％。在619例隐血阳性同时白细胞阴性的尿标本中，红细胞假阳性率为3．1％，白细胞假阴性率为5．5％。结论临床上使用干化学法做尿常规出现全阴性时，为了避免漏、误诊，必须进行显微镜沉渣检查。     

Alzheimer amyloid β-peptides exhibit ionophore-like properties in human erythrocytes

Abstract. There is growing evidence that the amyloid β-peptide (β₁_₄₀) is involved in the aetiology of Alzheimer's disease also implicating an altered calcium homeostasis of affected cells. Beta₁_₄₀ has been proposed to form calcium channels in synthetic bilayer membranes [1]. We wanted to investigate in the present study whether β₁-₄₀ (or fragments thereof) could act as ionophores in a biological membrane like the one in human erythrocytes. Incubation of the cells for 2h and 4h at 37°C together with 6μmolL^-1 of β₁-₄₀ or of fragments β₁_₂₈and β₂₅-₃₅, resulted in a significantly decreased energy charge qualitatively similar to the one obtained by a known calcium ionophore (A 23187, 0.05μmolL^-1). Moreover, β₁_₄₀ and its two fragments induced a significant alteration of ⁴⁵Ca permeability in human red blood cells of the same type as the one achieved by the calcium ionophore. The ionophoric action of β₁_₄₀ and its two fragments may lead to an increase of the intracellular calcium ion concentration, in turn resulting in enhanced Ca²⁺-ATPase activity and a decrease in energy charge. This may be valid also for neuronal plasma membranes and could, therefore, be a possible aetiological mechanism in Alzheimer's disease.     

红细胞冻干保存中的渗透性损伤实验研究

红细胞长期保存中保护剂添加、洗涤过程会引入红细胞渗透性损伤.在冻干保存研究中,由于多种保护剂同时使用,保护剂的类型和功能一直是研究的重点,但很少有从渗透性损伤角度分析保存方案合理性的报道.目前相关文献、专利中所用的保护剂总渗透压差别很大,细胞保存后回收率差异也较大.文中用NaCl溶液实验模拟红细胞保存中保护剂添加、洗涤过程.结果表明,选择合适的添加、洗涤方法可以在一定程度上减小渗透损伤.就红细胞而言,1.5Osmol/kg左右是保护剂总渗透压的一个重要阈值,总渗透压低于该阈值时,渗透性损伤较小;高于该阈值时,渗透损伤随着渗透压的增大而迅速增大.所以选择保护剂时,首先应该根据总渗透压来排除渗透压过高的保存方案,否则红细胞在添加和洗涤保护剂时已经损伤很大.该研究对其它细胞长期保存中保护剂的选择也具有参考意义.     

The Effect of Pentoxifylline on Erythrocyte Deformability and on Phosphatide Fatty Acid Distribution in the Erythrocyte Membrane

Summary

Ten maturity-onset diabetics with chronic vascular disease were treated with 400 mg pentoxifylline 3-times daily for 14 days. Erythrocyte deformability (using a filtration technique for whole blood) and phosphatide fatty acid distribution in the erythrocyte membrane were measured before and after the treatment period. Statistical analysis of the data showed that the erythrocyte filtration rate had increased significantly by the end of treatment (2a. = 0.02), and that there were only slight changes in erythrocyte membrane phosphatide fatty acid levels. The drug was well tolerated, and there were no adverse laboratory findings in the parameters measured. On the basis of results described by other investigators, the improvement in erythrocyte deformability was attributed to an increase in erythrocyte ATP levels. The authors discuss the importance of red cell fluidity for capillary perfusion.     

Determination of Urinary 3-Methoxy-4-Hydroxymandelic(Vanilmandelic) Acid by Electrophoresis at low pH

The high-voltage paper electrophoretic method of v. Studnitz for determination of 3-methosy-4-hydroxymandelic (vanilmandelic) acid in urine has been modified by performing the electrophoresis at low pH. The modified method is compared with the original one and found advantageous.     

Effect of Age,Weight, Race and Sex on Blood Pressure and Erythrocyte Sodium Pump Characteristics

In order to examine whether erythrocyte membrane handling of sodium is influenced by factors other than hypertension, measurements of red cell sodium transport were studied in one hundred normotensive volunteers. Erythrocyte sodium content was found to increase with increasing age, body weight and mean arterial pressure (MAP). It is also significantly correlated with age, body weight and MAP. Total sodium efflux was found to be reduced and negatively correlated with age and body weight. A reduction in ouabain-sensitive sodium efflux was also observed with increasing age and body weight. In males, the rate of ouabain-sensitive sodium efflux is higher than in females. Race was found to have no effect on erythrocyte electrolyte content and cationic flux rates of subjects. These data suggest that when studies in hypertension are going to be carried out, control subjects carefully matched for age, body weight and sex should be used if confounding results are not to be obtained.     

Abstracts from the XIIth Scientific Meeting of the Argentine Society of Arterial Hypertension

Epidemiologic Survillance of Cardiovascular Disease Mollar G, Cavalieri L, Galarza C, Waisman G, Beratarrechea A, Petrlik E, Langlois E, Soriano F, Marchetti M, and Gonzalez B de Quirós F Programas Médicos de Plan de Salud del Hospital Italiano de Buenos Aires

To enhance efficacy of health care, surveillance activities are required, especially with chronic prevalent diseases. Epidemiologic surveillance allows US to quantify and qualify health problems, settle priorities, identify high risk groups, manage and monitor health care systems, detect frequency changes in events, and assess performance of prevention and disease management programs. We have developed a surveillance system that identifies and reports daily on patients having cardiovascular disease (CVD) who are uncontrolled.

Objective: To evaluate the accomplishment of blood pressure (BP) measurement in people with CVD belonging to a health care system included in an epidemiological surveillance list.

Design: Cohort study between 1/1/2004 and 9/1/2004.

Methods: Patients 60 years old or older identified by surveillance system during the first term of 2004, were followed up. Patients were identified as having CVD through electronic medical record using international classification for primary attention (ICPA).

Patients are reported by the software system when presenting any of the following criteria: no blood pressure record during the past 6 months, blood pressure above 140/90 in the last record, and if diabetic A1C above 7.5%.

The connection with the appointment system allowed us to detect previously the patient’s attendance and, 15 min before his or her medical appointment, send the patient to be examined by the executors of a chronic disease program, according to the JNC VII guidelines.

The BP measurement is a common intervention to most chronic diseases because it increases cardiovascular risk, hence it is considered a process indicator of the surveillance system.

Results: Of the 24,411 patients having CVD, 5506 (26%) were listed during the first term, mean age was 74 years and 65% were female. By the end of 2004, 4660 (85%) patients had blood pressure recorded with an average values of 136.76 mmHg for systolic and 77.51 for diastolic blood pressure. Blood pressure was assessed three times in average.

Conclusion: Surveillance system allowed identifying of and intervening in a high proportion of patients.