Effectiveness of Antihypertensive Drugs in the Treatment of Hypertension in Pregnancy

The purpose of this open, prospective, randomized, comparative study was to examine the effectiveness of atenolol, a cardioselective beta₁ blocker, alphamethyldopa, an alpha-adrenergic antagonist, and ketanserin, a serotonin receptor antagonist, in the treatment of 90 patients (N–30 each) with severe chronic hypertension (ChH) during pregnancy or severe pregnancy-induced hypertension, with or without proteinuria in either case.

Arterial blood pressure (BP) for each drug group was analyzed at the onset of treatment, weekly for three weeks, and at the end of pregnancy. After one week of treatment a significant drop in BP was observed in the three groups of patients. Thereafter BP remained stable until the end of gestation, when a slight increase in BP was observed, especially in the group of patients treated with ketanserin.

No significant difference was observed between the groups in mean birthweight and perinatal morbidity and mortality. No adverse effects from the drugs on the fetus or newborn were observed. No significant difference was observed among the three drugs in their antihypertensive effect. However, given the relatively small numbers of patients studied, definitive statements regarding the relative efficacy and safety of alphamethyldopa, ketanserin and atenolol cannot be made. Thus, additional, larger controlled trials of these agents are required.     

Assessment of nitrate,nitrite and chloride in selected cured meat products and their exposure to school children in Brunei Darussalam

The readily available, good taste and easy to prepare cured meat products have become a prominent feature in children’s diet, leading to possible overconsumption of certain food additives. In this study, amount of nitrite, nitrate and salt, with mean values of 12.8 mg/kg, 20.2 mg/kg and 0.94 g/100 g, respectively and their intake from consumption of cured meat products (sausages, salamis, meatloaves and meatballs), were estimated for 2339 school children. The estimated salt intake for overall children was 0.53–1.01 g/day, where none of the children’s salt intake exceeded their age group’s Tolerable Upper Intake level. While the average estimated intake of nitrate and nitrite were at 0.08 mg/kg b.w/day and 0.05 mg/kg b.w/day, respectively. Based on the above estimation, ∼20% of the total children exceeded the Acceptable Daily Intake (ADI) of nitrite of 0.07 mg/kg b.w/day while none of the children exceeded the ADI of nitrate of 3.7 mg/kg b.w/day.     

一起蓄意投放亚硝酸盐引发中毒事件的现场流行病学调查

目的 <\b>通过对一起蓄意投放亚硝酸盐引起食物中毒的现场流行病学调查和刑事侦查比较,加强流行病学方法的应用.方法 <\b>按照定义进行病例搜索,完成所有病例或知情者基本信息、发病情况和饮食史等面对面调查,获取食品原料、加工和销售等情况；采集样本检测亚硝酸盐.查阅有关资料和知情访谈,了解刑侦和司法调查结果.结果 <\b>中毒总罹患率为56.25％(63/112),其中疑似和确证病例罹患率分别为41.96％和14.28％,病死率为3.17％(2/63).临床表现和疗效符合亚硝酸盐急性食物中毒特征；发病时间集中,与年龄、性别和职业无关.病例呕吐物、食物和环境样品共7批次191份,亚硝酸盐检测阳性率为18.84％.现场环境、食品经销和加工流程调查结果,支持亚硝酸盐经蓄意性投放的结论.刑事侦查结果表明,疑犯意图源于市场经营之争,购买亚硝酸盐在饮食摊档投放.结论 <\b>该起蓄意投放亚硝酸盐引起食物中毒的事件,经由现场流行病学调查和刑事侦查密切配合,获得充分的证据.刑事侦察与现场流行病学的配合在此类事件中的应用值得重视.     

Mechanistic exploration of quercetin against metronidazole induced neurotoxicity in rats: Possible role of nitric oxide isoforms and inflammatory cytokines

AimMetronidazole, a nitroimidazole derived antibiotic used to treat many bacterial infections, is reported to penetrate the blood brain barrier after long term administration resulting into neuronal toxicity. Further, quercetin, a polyphenol flavonoid is reported to exhibit neuroprotective activity but its pharmacodynamics interaction against metronidazole induced neurotoxicity. Therefore, the present study was designed to evaluate the postulated mechanism of metronidazole induced neurotoxicity and potential neuroprotective role of quercetin.Main methodsAnimals (Sprague Dawley) rats were randomly divided into five groups such as control, metronidazole (135 mg/kg), quercetin (100 mg/kg), metronidazole (135 mg/kg) + quercetin (50 mg/kg), and metronidazole (135 mg/kg) + quercetin (100 mg/kg). The brain tissues were evaluated for tissue cyclo-oxygenase, lipoxygenase, nitrite levels, inflammatory and antioxidant biomarkers. The brain tissues were further scrutinized histopathologically for neuronal degeneration. Western blotting analysis was performed for the localization of protein expression for Bax, Bcl₂, iNOS, eNOS and caspase-3.Key findingsThe metronidazole significantly alters the antioxidant levels, inflammatory mediators and morphological changes in the brain tissue. Metronidazole also induces iNOS, Bax and caspase 3 protein expressions whilst decreases the expression of Bcl₂ and eNOS in the brain tissue. Metronidazole administration causes a momentous increase in tissue inflammatory markers.SignificanceThe metronidazole (oral) administration causes remarkably neurotoxicity effects and the same could be attributed to the fact that metronidazole has the ability to cross the blood brain barrier and transforms the enzymatic activity of various biomarkers present in the brain. From the results, it could be hypothesized that metronidazole causes neurotoxicity by hindering the proportion of antioxidants in the brain tissue and inducing nitric oxide synthesis along with apoptosis. However, quercetin demonstrated a significant protective effect on neuronal toxicity precipitated through metronidazole.     

Toxicity of ammonia,nitrite and nitrate to Litopenaeus vannamei juveniles in low-salinity water in single and ternary exposure experiments and their environmental implications

Information on toxicity of nitrogen compounds for Litopenaeus vannamei in coastal ecosystems and culture under low salinity is scarce. Acute toxicity trials were conducted in L. vannamei to determine the single and combined effects of ammonia, nitrite and nitrate at a salinity of 3 g/L. The 96 h-LC₅₀ was 29.0 mg/L for total ammonia nitrogen (TAN); 10.6 mg/L for nitrogen as nitrite (NO₂⁻-N); and 900 mg/L for nitrogen as nitrate (NO₃⁻-N). The joint effects of ammonia, nitrite and nitrate exposure were antagonistic at 24–72 h; and additive from 72 to 96 h. The proposed safety levels of single exposure to TAN, NO₂⁻-N and NO₃⁻-N for L. vannamei are 1.45, 0.53 and 45.0 mg/L, respectively. When in mixture, the proposed level of TAN/NO₂⁻-N/NO₃⁻-N is 0.05 TU (Toxicity Unit) corresponding to 0.48, 0.08 and 14.6 mg/L of TAN, NO₂⁻-N and NO₃⁻-N, respectively.     

Toxicity of Un-ionized Ammonia,Nitrite, and Nitrate to Juvenile Bay Scallops, <Emphasis Type="Italic">Argopecten irradians irradians</Emphasis>

Juvenile bay scallops (7.2–26.4 mm) were exposed for 72 h to different concentrations of un-ionized ammonia, nitrite, or nitrate. Using the Trimmed Spearman Karber method, 50% lethal concentrations (LC₅₀) and 95% confidence limits were calculated individually for each. Un-ionized ammonia concentrations above 1.0 mg N-NH₃/L resulted in 100% scallop mortality within 72 h. The 72-h LC₅₀ for un-ionized ammonia was calculated at 0.43 mg N/L. At nitrite concentrations of 800 mg N/L or higher 100% mortality was observed. The 72-h LC₅₀ for nitrite was calculated at 345 mg N/L. Nitrate was the least toxic, with 100% mortality observed at a concentration of 5000 mg N/L. The calculated nitrate 72-h LC₅₀ was 4453 mg N/L. Our results indicate that un-ionized ammonia is the most lethal nitrogenous waste component to bay scallops.     

硝酸吸入闭塞性细支气管炎小鼠模型的建立和评价

目的 探索硝酸吸入法建立小鼠闭塞性细支气管炎的方法.方法 将无特定病原体(SPF)级BALB/c小鼠(6～8周,雌雄各半)按随机数字表法分为两组:对照组和模型组(BO组),每组18只.模型组构建采用10％硝酸溶液气雾剂连续3h吸入1次,对照组采用吸入蒸馏水代替,其余实验条件相同.分别在建模后1周、2周、6周收集样本,留取BALF,左肺行病理学检测.饲养期间观察小鼠一般状态,监测两组小鼠体质量变化,肺功能情况.结果 模型组小鼠吸入硝酸后即刻出现气促、食欲不振、毛发卷曲等症状,并且在3～7 d时达到高峰,同时体质量降至最低,气道阻力升至最高;1周后小鼠的一般状态明显好转,体质量逐渐增加,气道阻力逐渐减小;此外,造模1周时BALF中炎性细胞明显增加,6周时BALF中炎性细胞较1周时减少;肺组织HE染色可见3～7 d时支气管周围大量炎性细胞浸润;1～4周逐渐出现气道上皮细胞增生,气道壁结构破坏,平滑肌增生,管壁增厚,管腔缩窄;6周时支气管周边出现纤维化.病理改变符合感染后闭塞性细支气管炎的病理改变.结论 给予BALB/c小鼠雾化吸入10％硝酸溶液可以成功建立BO小鼠模型.     

Concepts of hypoxic NO signaling in remote ischemic preconditioning

Acute coronary syndromes remain a leading single cause of death worldwide. Therapeutic strategies to treat cardiomyocyte threatening ischemia/reperfusion injury are urgently needed. Remote ischemic preconditioning (rIPC) applied by brief ischemic episodes to heart-distant organs has been tested in several clinical studies, and the major body of evidence points to beneficial effects of rIPC for patients. The underlying signaling, however, remains incompletely understood. This relates particularly to the mechanism by which the protective signal is transferred from the remote site to the target organ. Many pathways have been forwarded but none can explain the protective effects completely. In light of recent experimental studies, we here outline the current knowledge relating to the generation of the protective signal in the remote organ, the signal transfer to the target organ and the transduction of the transferred signal into cardioprotection. The majority of studies favors a humoral factor that activates cardiomyocyte downstream signaling - receptor-dependent and independently. Cellular targets include deleterious calcium (Ca²⁺) signaling, reactive oxygen species, mitochondrial function and structure, and cellular apoptosis and necrosis. Following an outline of the existing evidence, we will furthermore characterize the existing knowledge and discuss future perspectives with particular emphasis on the interaction between the recently discovered hypoxic nitrite-nitric oxide signaling in rIPC. This refers to the protective role of nitrite, which can be activated endogenously using rIPC and which then contributes to cardioprotection by rIPC.     

A new redox-dependent mechanism of MMP-1 activity control comprising reduced low-molecular-weight thiols and oxidizing radicals

Matrix metalloproteinases (MMPs), a family of zinc-dependent proteinases, participate in remodeling and degradation of the extracellular matrix proteins. The activity of MMPs is thought to be predominately posttranslationally regulated via proteolytic activation of precursor zymogens or via their naturally occurring endogenous inhibitors. Here, using recombinant MMP-1, we investigated new redox-dependent mechanisms of proteinase activity regulation by low-molecular-weight thiols. We find that glutathione (GSH), cysteine, homocysteine, and N-acetylcysteine at physiological concentrations competitively reduce MMP-1 activity up to 75% with an efficiency of cysteine ≥ GSH > homocysteine > N-acetylcysteine. In contrast, S-derivatized thiols completely lack this inhibitory activity. Interestingly, the competitive GSH-mediated inhibition of MMP-1-activity can be fully reversed abrogated by oxidizing radicals like ^•NO₂ or Trolox radicals, here generated by UVA irradiation of nitrite or Trolox, two relevant agents in human skin physiology. This redox-dependent reactivation of the inactive GSH–MMP-1-complex comprises GSH oxidation and is significantly inhibited in the presence of ascorbic acid, an effective ^•NO₂ and Trolox radical scavenger. We here offer a new concept of redox-sensitive control of MMP-1 activity based on the inhibitory effect of reduced thiols and reactivation by a mechanism comprising derivatization or oxidation of the MMP-1-bound inhibitory-acting thiol.