Further studies on the possibility of differential demonstration of radicals of sulphur-containing amino-acids.

The authors showed that in rat liver and brain sections with blocked SH groups and split S-S bonds mercury orange stains some tissue structures after treating the sections with BAL. Considering that the blockade of SH groups with N-ethylmaleimide in is stable the authors set forth the hypothesis that the use of BAL may enable the demonstration of a sulphur-containing amino-acid which is devoid of SH or SS groups but acquires them only when acted upon by BAL. The in vitro studies demonstrated that the effect of BAL makes it possible to stain methionine with mercury orange which otherwise does not stain this amino-acid.     

丙种球蛋白联合注射用甲泼尼龙琥珀酸钠治疗重症手足口病患儿的临床研究

目的:探讨丙种球蛋白联合注射用甲泼尼龙琥珀酸钠治疗重症手足口病(HFMD)患儿的临床效果。方法:选择我院2013年1月至2014年1月收治的重症HFMD患儿80例,按随机数字表法平均分为两组,研究组及对照组各40例。对照组患者在常规治疗基础上给予甲泼尼龙琥珀酸钠治疗,研究组患者给予丙种球蛋白联合注射用甲泼尼龙琥珀酸钠治疗,比较两组患儿治疗疗效,发热、疱疹、神经系统受累症状消退时间及住院时间。结果:研究组患儿治疗总有效率为97.5%,明显高于对照组87.5%,比较差异具有统计学意义(x2=3.85,P0.05)。研究组患儿发热消退时间、疱疹消退时间、神经系统受累症状消退时间及住院时间均明显短于对照组,比较差异具有统计学意义(均P0.05)。结论:丙种球蛋白联合注射用甲泼尼龙琥珀酸钠治疗重症HFMD患儿疗效显著,可有效改善患儿临床症状,值得临床推广应用。     

Some complexes of 2.3-Dimercaptopropanol (BAL) with gold(I) and gold(III)

2, 3-Dimercaptopropanol (BAL) reacted with the tetrachloroaurate ion in solution to form a series of insoluble polymers of definite stoichiometry. Both gold(I) and gold(III) have been identified in these compounds. Reaction of BAL with the tetrabromoaurate ion and with thiomalic acid and D-penicillamine complexes of gold also produced insoluble precipitates. However, with an L-cysteine complex of gold no precipitate was isolated, although there was evidence of replacement of cysteine with BAL. The implications of these results for the use of BAL in cases of gold toxicity are discussed     

Influence of Methionine on Toxicity of Fluoride in the Liver of Rats

Oxidative stress is a common mechanism by which chemical toxicity can occur in the liver. The aim of the studies conducted has been to determine what influence the administration of methionine during intoxication with sodium fluoride may have upon the selected enzymes of the antioxidative system in rat liver. The experiment was carried out on Wistar FL rats (adult females) that, for 35 days, were administered distilled water, NaF, or NaF with methionine (doses: 10 mg NaF/kg bw/day, 10 mg Met/kg bw/day). The influence of administered NaF and Met was examined by analyzing the activity of the antioxidative enzymes: superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione transferase in the liver. The results suggest that fluoride reduces the efficiency of the enzymatic antioxidative system in the liver. Administration of methionine during intoxication with sodium fluoride does not have an advantageous influence upon the activity of superoxide dismutase, catalase, reductase, and glutathione transferase in the liver. The slight increase of the activity of glutathione peroxidase after administration of methionine may indicate its protective influence upon that enzyme.     

Investigations into the Mechanism of 2,3-Dimercaptopropanol Neurotoxicity

2,3 dimercaptopropanol (BAL), is a dithiol chelating agent, used for the treatment of heavy metal intoxication; however, this compound has low therapeutic efficacy and in some situations may cause neurotoxic effects. In experimental models, administration of high doses of BAL produces seizures that culminate in animal death. However, investigations on the modulation of neurotransmitter system(s) involved in BAL-induced seizures are still lacking in the literature. In the present study, the neurotoxicity of BAL, as measured by the manifestation of seizures was examined and the modulation of glutamatergic and GABAergic receptors and ion channels potentially involved in BAL-induced seizures was investigated. The results demonstrated that BAL (18.6 mg/kg) induced seizures and all mice died within one day. GABAergic allosteric modulators (3 or 12 mg/kg diazepam and 50 mg/kg phenobarbital) blocked the appearance of seizure and reduced almost completely the death caused by BAL. Carbamazepine (5 mg/kg) significantly reduced the incidence of BAL-induced seizures, while sodium valproate and MK-801 were not effective in reducing the incidence of seizures. Valproate (300 mg/kg) and MK-801(0.5 mg/kg) prolonged the latencies for onset of seizures; however, all animals died within one day after BAL administration. High doses of ZnCl₂ (135 mg/kg) blocked the appearance of seizures episodes, but no animal survived more than one day. The content of total non-protein—SH in brain of mice treated with 18.6 and 124 mg/kg BAL increased from 0.9 ± 0.3 nmol/g (control animals) to 1.7 ± 0.3 and 3.5 ± 0.8 nmol/g, respectively. In vitro, 0.1–1 mM concentrations of BAL inhibited [³H]glutamate and [³H]MK-801 binding, but increased the binding of [³H]muscimol to brain synaptic plasma membrane. The results reported here demonstrate that GABAergic allosteric modulators (diazepam and phenobarbital) and carbamazepine, a compound that acts by prolonging the recovery of voltage-activated ion channels from inactivation, are able to abolish BAL-induced seizures, while the NMDA antagonist (MK-801) prolonged the latencies for onset of seizures suggesting that modulators of this subtype of glutamate receptor have a modest role on BAL-induced seizures. The results of the present study suggest that allosteric modulators of GABAergic system and carbamazepine, a voltage-gated Na⁺-channel antagonist, should be considered for the treatment of animals or patients intoxicated with BAL.     

Coxiella burnetii, the agent of Q fever in Brazil: its hidden role in seronegative arthritis and the importance of molecular diagnosis based on the repetitive element IS1111 associated with the transposase gene

Coxiella burnetii is the agent of Q fever , an emergent worldwide zoonosis of wide clinical spectrum. Although C. burnetii infection is typically associated with acute infection, atypical pneumonia and flu-like symptoms, endocarditis, osteoarticular manifestations and severe disease are possible, especially when the patient has a suppressed immune system; however, these severe complications are typically neglected. This study reports the sequencing of the repetitive element IS1111 of the transposase gene of C. burnetii from blood and bronchoalveolar lavage (BAL) samples from a patient with severe pneumonia following methotrexate therapy, resulting in the molecular diagnosis of Q fever in a patient who had been diagnosed with active seronegative polyarthritis two years earlier. To the best of our knowledge, this represents the first documented case of the isolation of C. burnetii DNA from a BAL sample.     

Flow cytometric analysis reveals the high levels of platelet activation parameters in circulation of multiple sclerosis patients

Methionine is an essential amino acid involved in critical metabolic process, and regulation of methionine flux through metabolism is important to supply this amino acid for cell needs. Elevation in plasma methionine commonly occurs due to mutations in methionine-metabolizing enzymes, such as methionine adenosyltransferase. Hypermethioninemic patients exhibit clinical manifestations, including neuronal and liver disorders involving inflammation and tissue injury, which pathophysiology is not completely established. Here, we hypothesize that alterations in macrophage inflammatory response may contribute to deleterious effects of hypermethioninemia. To this end, macrophage primary cultures were exposed to methionine (1 mM) and/or its metabolite methionine sulfoxide (0.5 mM), and M1/proinflammatory or M2/anti-inflammatory macrophage polarization was evaluated. In addition, inflammation-related pathways including oxidative stress parameters, as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities; reactive oxygen species (ROS) production, and purinergic signaling, as ATP/ADP/AMPase activities, were investigated. Methionine and/or methionine sulfoxide induced M1/classical macrophage activation, which is related to proinflammatory responses characterized by increased iNOS activity and TNF-α release. Further experiments showed that treatments promoted alterations on redox state of macrophages by differentially modulated SOD and CAT activities and ROS levels. Finally, methionine and/or methionine sulfoxide treatment also altered the extracellular nucleotide metabolism, promoting an increase of ATPase/ADPase activities in macrophages. In conclusion, these findings contribute to better understand the participation of proinflammatory responses in cell injury observed in hypermethioninemic patients.     

Nijmegen breakage syndrome (NBS)

Most inborn errors of metabolism (IEM) are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.). IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects), and metal (hemochromatosis) and storage disorders (cystinosis). Non-autoimmune diabetes mellitus, thyroid dysfunction and/or goiter and sometimes hypoparathyroidism should steer the diagnosis towards a respiratory chain defect. Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes), whereas primary hypogonadism is reported in Alstr?m disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction) and galactosemia. Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure), congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last). This is a new and growing field and is not yet very well recognized in adulthood despite its consequences on growth, bone metabolism and fertility. For this reason, physicians managing adult patients should be aware of these diagnoses.     

食管癌术后并发症及其处理

食管癌是我国一种常见的消化道恶性肿瘤,居世界癌症死因第7位,中国癌症死因第4位。其中以中段鳞状细胞癌多见,临床表现以晚期进行性吞咽困难为主,确诊主要以胃镜病理活检为金标准,其治疗方法主要有手术、放疗、化疗及分子靶向治疗等。但目前治疗上仍然以手术为主,术前术后放化疗为辅。然而,随着手术在食管癌治疗中适应症的不断扩大、根治性手术淋巴结的扩大清扫及拥有基础疾病高龄患者的增多,术后并发症的发生率不可避免的随之增加。本文将重点阐述吻合口瘘、吻合口狭窄、呼吸及心血管并发症、乳糜胸、胃排空障碍、膈疝、喉返神经损伤及单纯脓胸、严重腹泻、呕血等食管癌术后常见、严重并发症的病因、临床表现与诊断、治疗及其预防。通过对食管癌术后并发症的充分认识及有效预防,从而对食管癌手术成功率及患者术后生存质量的提高、肿瘤预后的改善起到了重要作用。     

冷刀系统与宫腔镜下能量系统分别联合芬吗通治疗中重度宫腔粘连疗效对比

摘要 目的：对比分析冷刀系统与宫腔镜下能量系统分别联合芬吗通治疗中重度宫腔粘连疗效。方法：选取2020年1月-2022年1月我院收治的中重度宫腔粘连患者80例为研究对象,分为对照组（n=40）和观察组（n=40）。对照组采用宫腔镜下能量系统联合芬吗通治疗,观察组采用冷刀系统联合芬吗通治疗。对比两组临床指标、临床疗效、月经恢复情况、并发症发生情况。结果：观察组手术时间、术中出血量、手术次数、术后出血量均短/少于对照组（P<0.05）。术后12个月观察组临床疗效（90.00%）显著高于对照组（65.00%）（P<0.05）。术后8~14个月两组的月经恢复情况均改善,观察组月经恢复情况较对照组更优（P<0.05）。观察组术后感染、子宫腺肌病、子宫穿孔、水中毒等并发症的总发生率（7.50%）低于对照组（47.50%）（P<0.05）。结论：冷刀系统联合芬吗通治疗宫腔粘连具有显著疗效,不仅对患者的危害更小,还有利于月经恢复,减少并发症,改善预后。     

Barbiturate Intoxication: Morbidity and Mortality

The complications encountered in caring for 185 patients intoxicated with barbiturates were reviewed. The population consisted of 142 patients with long-acting barbiturate concentrations of 8 mg per 100 ml or greater, 20 patients with short-acting barbiturate concentrations of 3 mg per 100 ml or greater and 23 consecutive patients with short-acting barbiturate intoxication referred for monitoring. Pneumonia was the major cause of morbidity and mortality and correlated best with the initial depth of coma and the use of an endotracheal tube in treatment. Cardiovascular instability manifested by pulmonary edema was the next leading cause of morbidity and mortality and correlated best with the initial depth of coma and the quantity of intravenous fluid administered. In retrospect, use of eliminative measures such as dialysis would probably not have altered the outcome in most of the patients who died and attempts at forced diuresis may have contributed to several deaths. Particular emphasis should be placed on the problems of sepsis and fluid therapy in the management of these patients.     

Comparative diffusion of 14C-ethionine and 14C-methionine in rat tissue]

The pancreas is the tissue which traps the most intensively the trace-dosis injected ethionine -14C; 30 min after the injection, the pancreas fixes the labelled product twice more than the liver and five times more than the stomach. This trapping might explain the pancreatic modifications occuring during the intoxication. In the same experimental conditions, the pancreas fixes the ethionine -14C twice less than methionine. Urinary excretion of ethionine is faster and more important than that of methionine.     

老年人急性胆道感染(附68例临床分析)

目的:探讨老年人急性胆道感染的临床特点及诊疗经验。方法:回顾性分析68例老年人急性胆道感染的诊断和治疗的临床资料。结果:老年人急性胆道感染病人并发症多,使病情危重复杂,影响手术的安全性和术后的恢复。甚至手术效果良好的病人术后死于并发症的严重发作,多数患者预后不佳。结论:老年人具有特殊的生理特点与临床特点,急性胆道感染时临床表现多不典型。年龄不是手术禁忌证,应在积极抗感染、抗休克的同时,尽早采取恰当的手术治疗,做好围手术期的处理才能提高治疗效果,降低病死率。     

Das Marfan-Syndrom und verwandte monogene Krankheiten der Aorta

Marfan syndrome (MFS) is an autosomal dominant, pleiotropic disease of the connective tissue with a prevalence of about 1 in 5000 persons. MFS is characterized by manifestations in the cardiovascular system, eye, skeleton, lung, skin, and dura mater that show a high degree of intra- and interfamilial variability. Many manifestations develop during or shortly before puberty; severe complications rarely occur before adulthood. Many patients with MFS display a so-called marfanoid habitus with tall stature, dolichostenomelia (long, narrow extremities), dolichocephaly (disproportionately long and narrow head), as well as other skeletal abnormalities such as scoliosis and pes planus. Scoliosis occurs in approximately 60% of those affected, pectus deformities in up to two thirds. Ectopia lentis is seen in many patients with MFS and is almost always bilateral. MFS is characterized by a high risk for complications such as severe scoliosis or pectus deformities, spontaneous pneumothorax, retinal detachment, or glaucoma secondary to lens luxation. The most severe complications occur in the cardiovascular system, including in particular acute dissection of the ascending aorta, which generally follows a long period of progressive aortic dilatation. Before the introduction of modern treatment modalities, the average life expectancy of persons with MFS was estimated to be 32 years. Today, with medical care in multidisciplinary centers, an average life expectancy of over 60 years can be achieved. This article offers a review of established and novel concepts for the diagnosis and treatment of MFS and other hereditary diseases of the aorta.     

Cell profiles in serial bronchoalveolar lavage after human heart-lung transplantation.

The aim of this study was to investigate serial changes in bronchoalveolar lavage (BAL) cell profiles after human heart-lung transplantation and to assess the clinical value of BAL cytology in the differential diagnosis of complications in the transplanted lung. BAL was performed serially on 23 occasions on four patients. Elevated counts of neutrophils (4-48%) were observed in all preparations, with peak values in the early postoperative phase, in bacterial infections and in cytomegalovirus pneumonitis. In the last condition, BAL cytology also showed relative lymphocytosis (less than or equal to 50%) with high proportions (less than or equal to 50%) of HLA DR-positive T lymphocytes. No characteristic light microscopic pattern was observed in acute pulmonary rejection. However, scanning electron microscopy revealed elevated counts (greater than 5%) of "villous" macrophages in BAL obtained during or shortly after episodes of rejection. BAL cytology may be helpful in differentiating viral and bacterial infections, while scanning electron microscopy seems to be more suitable to the diagnosis of acute pulmonary rejection.     

Influence of Methionine and Vitamin E on Fluoride Concentration in Bones and Teeth of Rats Exposed to Sodium Fluoride in Drinking Water

Increased exposure to fluorine-containing compounds leads to accumulation of fluorides in hard tissues of bones and teeth, which may result in numerous skeletal and dental disorders. This study evaluates the influence of methionine and vitamin E on fluoride concentration in bones and teeth of rats subjected to long-term exposure to sodium fluoride in drinking water. The study was conducted in 30 3-month-old female Wistar FL rats. The animals were divided into five groups, six rats per group. The control group consisted of rats receiving only distilled water as drinking water. All other groups received NaF in the amount of 10 mg/kg of body mass/day in their drinking water. In addition, respective animal groups received: NaF + Met group—10 mg of methionine/kg of body mass/day, NaF + Met + E group—10 mg of methionine/kg of body mass/day and 3 mg of vitamin E (tocopheroli acetas)/rat/day and NaF + E group—3 mg of vitamin E/rat/day. Femoral bones and incisor teeth were collected for the study, and the fluoride concentration was determined using a fluoride ion-selective electrode. Fluoride concentration in both bones and teeth was found to be higher in the NaF and NaF + Met groups compared to the control group. In groups NaF + Met + E and NaF + E, the study material contained much lower fluoride concentration compared to the NaF group, while the effect was more prominent in the NaF + E group. The results of the studies indicate that methionine and vitamin E have opposite effects on accumulation of fluorides in hard tissue in rats. By stimulating fluoride accumulation, methionine reduces the adverse effect of fluorides on soft tissue, while vitamin E, which prevents excessive accumulation of fluorides in bones and teeth, protects these tissues from fluorosis. Therefore, it seems that combined application of both compounds would be optimal for the prevention of the adverse effects of chronic fluoride intoxication.     

Biochemistry of homocysteine in health and diseases

The amino acid homocysteine (Hcy), formed from methionine has profound importance in health and diseases. In normal circumstances, it is converted to cysteine and partly remethylated to methionine with the help of vit B12 and folate. However, when normal metabolism is disturbed, due to deficiency of cystathionine-beta-synthase, which requires vit B6 for activation, Hcy is accumulated in the blood with an increase of methionine, resulting into mental retardation (homocystinuria type I). A decrease of cysteine may cause eye diseases, due to decrease in the synthesis of glutathione (antioxidant). In homocystinurias type II, III and IV, there is accumulation of Hcy, but a decrease of methionine, thus, there is no mental retardation. Homocysteinemia is found in Marfan syndrome, some cases of type I diabetes and is also linked to smoking and has genetic basis too. In hyperhomocysteinemias (HHcys), clinical manifestations are mental retardation and seizures (type I only), ectopia lentis, secondary glaucoma, optic atrophy, retinal detachment, skeletal abnormalities, osteoporosis, vascular changes, neurological dysfunction and psychiatric symptoms. Thrombotic and cardiovascular diseases may also be encountered. The harmful effects of homocysteinemias are due to (i) production of oxidants (reactive oxygen species) generated during oxidation of Hcy to homocystine and disulphides in the blood. These could oxidize membrane lipids and proteins. (ii) Hcy can react with proteins with their thiols and form disulphides (thiolation), (iii) it can also be converted to highly reactive thiolactone which could react with the proteins forming -NH-CO- adducts, thus affecting the body proteins and enzymes. Homocystinuria type I is very rare (1 in 12 lakhs only) and is treated with supplementation of vit B6 and cystine. Others are more common and are treated with folate, vit B12 and in selected cases as in methionine synthase deficiency, methionine, avoiding excess. In this review, the role of elevated Hcy levels in cardiovascular, ocular, neurologial and other diseases and the possible therapeutic measures, in addition to the molecular mechanisms involved in deleterious manifestations of homocysteinemia, have been discussed.     

Oxidative stress in vivo and in vitro: modulation by quartz dust and hyperbaric atmosphere.

Changes in the oxidative status in the soluble proteins of bronchoalveolar lavage (BAL) fluid from monkeys were examined during 26 months of individual or combined exposure to quartz dust (5 mg/m3 of DQ12) and a hyperbaric atmosphere (2.5 bar). The oxidation of BAL proteins, assumed to be an indicator for oxidative stress in the lungs, was determined by measuring the amount of carbonyl groups in their amino acid side chains. The carbonyl content of BAL proteins (nmol carbonyl/mg protein) increased steadily to a maximum value of 156% of the control after 6 months exposure to hyperbaric atmosphere, and decreased below 50% of control levels in both the quartz alone exposed group and the group exposed to quartz in combination with a hyperbaric atmosphere. The effect of quartz on the production of reactive oxygen species by BAL cells was investigated in vitro. BAL cells from healthy monkeys preincubated with quartz and stimulated with phorbol-myristate acetate (PMA) produced reduced levels of extracellular superoxide anion and intracellular hydrogen peroxide compared with PMA-only stimulated cells. Thus the lowered carbonyl content of BAL proteins in the quartz exposed groups may have resulted from reduced production of the hydrogen peroxide which is essential for carbonyl formation by phagocytes. Changes in carbonyl content of BAL protein in vivo may be a new indicator for potential subsequent lung damage.     

Allergen-specific Th1 cells counteract efferent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation partly via IFN-gamma

Th2 T cell immune-driven inflammation plays an important role in allergic asthma. We studied the effect of counterbalancing Th1 T cells in an asthma model in Brown Norway rats that favors Th2 responses. Rats received i.v. transfers of syngeneic allergen-specific Th1 or Th2 cells, 24 h before aerosol exposure to allergen, and were studied 18-24 h later. Adoptive transfer of OVA-specific Th2 cells, but not Th1 cells, and OVA, but not BSA exposure, induced bronchial hyperresponsiveness (BHR) to acetylcholine and eosinophilia in a cell number-dependent manner. Importantly, cotransfer of OVA-specific Th1 cells dose-dependently reversed BHR and bronchoalveolar lavage (BAL) eosinophilia, but not mucosal eosinophilia. OVA-specific Th1 cells transferred alone induced mucosal eosinophilia, but neither BHR nor BAL eosinophilia. Th1 suppression of BHR and BAL eosinophilia was allergen specific, since cotransfer of BSA-specific Th1 cells with the OVA-specific Th2 cells was not inhibitory when OVA aerosol alone was used, but was suppressive with OVA and BSA challenge. Furthermore, recipients of Th1 cells alone had increased gene expression for IFN-gamma in the lungs, while those receiving Th2 cells alone showed increased IL-4 mRNA. Importantly, induction of these Th2 cytokines was inhibited in recipients of combined Th1 and Th2 cells. Anti-IFN-gamma treatment attenuated the down-regulatory effect of Th1 cells. Allergen-specific Th1 cells down-regulate efferent Th2 cytokine-dependent BHR and BAL eosinophilia in an asthma model via mechanisms that depend on IFN-gamma. Therapy designed to control the efferent phase of established asthma by augmenting down-regulatory Th1 counterbalancing mechanisms should be effective.