Ginkgo biloba leaf extract improves the cognitive abilities of rats with D-galactose induced dementia

Standardized Ginkgo biloba leaf extract has been used in clinical trials for its beneficial effects on brain functions,particularly in dementia.Substantial experimental evidences indicated that Ginkgo biloba leaf extract (EGB) protected neuronal cells from a variety of insults.We investigated the effect of EGB on cognitive ability and protein kinase B (PKB) activity in hippocampal neuronal cells of dementia model rats.Rats received an intraperitoneal injection of D-galactose to induce dementia.Forty-eight Spraque-Dawley rats were randomly divided into six groups,including the control group,D-galactose group (Gal),low-dose EGB group (EGB-L),mid-dose EGB group (EGB-M),high-dose EGB group (EGB-H) and treatment group.The EGB-L,EGB-M and EGB-H groups were administered with EGB and D-galactose simultaneously.Y-maze,cresyl violet staining,TUNEL assays and immunohistochemistry staining were performed to detect learning and memory abilities,morphological changes in the hippocampus,neuronal apoptosis and the expressing level of phospho-PKB,respectively.Rats in the Gal group showed decreased abilities of learning and memory,and hippocampal pyramidal cell layer was damaged,while EGB administration improved learning and memory abilities.The Gal group exhibited many stained,condensed nuclei and micronuclei,either isolated or within the cytoplasm of cells (39.5±1.4).Apoptotic cells decreased in the groups of EGB-L (35.9±0.9),EGB-M (16.8±1.0) and EGB-H (10.1±0.8),and there were statistical significances compared with the Gal group.Immunoreactivity of phospho-PKB was localized diffusely throughout the cytosol of cells in all groups,while the immunoreactivity of the Gal group was weak.EGB significantly attenuated learning and memory impairment in a dose-dependent manner,while it could decrease the nmber of TUNEL-positive cells,and increase the activity of PKB.Our results demonstrated that EGB attenuated memory impairment and cell apoptosis in galactose-induced dementia model rats by activating PKB.     

人参皂苷Rb3对心肌缺血再灌注损伤模型大鼠的保护

BACKGROUND: Ginsenoside Rb3 has a variety of physiological activities, which mainly reflected in the cardiovascular treatment. OBJECTIVE:To study the protective effects of ginsenoside Rb3 on the ischemia/reperfusion injury of rats. METHODS: 120 Sprague-Dawley rats were randomly assigned to six groups, with 20 in each group. Rats in the model and sham operation groups were intragastrically given physiological saline 2 mL/kg•d for 2 consecutive days. Rats in the positive drug group were intragastrically given diltiazem 2 mL/kg•d for 2 consecutive days. Rats in the low-dose drug group, moderate-dose drug group and high-dose drug group were intragastrically given ginsenoside Rb3 10, 20, 30 mg/kg•d, for 2 consecutive days. At 2 days after administration, the chest of rats in the sham operation was opened, but these rats did not receive any other treatment. In other five groups, anterior descending branch of left coronary artery was ligated to establish models of ischemia/reperfusion injury. 48 hours later, we observed pathological sections of rat cardiac muscle, calculated percentage of organ coefficient and myocardial infarction area, measured the levels of serum isozyme, malondialdehyde, lactate dehydrogenase, endothelial relaxing factor, superoxide dismutase and glutathione peroxidase. RESULTS AND CONCLUSION: (1) Pathological sections: ginsenoside Rb3 significantly improved the ischemia/reperfusion injury. (2) Percentages of organ coefficient and myocardial infarction area: compared with the model group, the percentages were significantly lower in the moderate-dose and high-dose drug groups (P < 0.05, P < 0.01). (3) Serum indexes: compared with the model group, ginsenoside Rb3 decreased isozyme, malondialdehyde, lactate dehydrogenase and endothelial relaxing factor levels in a dose-dependent manner, but increased superoxide dismutase and glutathione peroxidase levels in a dose-dependent manner. (4) Results suggested that ginsenoside Rb3 has protective effects on ischemia/reperfusion injury. Its mechanism of action may be associated with anti-lipid peroxide activities in cells, the anti-free radical effects, anti-inflammatory functions and the influence of cardiac enzymes on energy metabolism. 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程     

健步虎潜丸含药血清对体外成骨样细胞增殖和功能的影响

BACKGROUND: More recently, the focus has been on searching for a compound Chinese medicine for reinforcing kidney, which cannot only inhibit bone absorption, but also promote osteogenesis to protect against osteoporosis. OBJECTIVE: To explore effects of drug serum of Jianbuhuqian pills on proliferation and function of osteoblast-like cells in vitro. METHODS: Twenty-four adult female Sprague-Dawley rats were randomly divided into low-dose, medium-dose, high-dose and normal saline groups, and given intragastric administration of 1.5, 3.0, and 6 g/kg Jianbuhuqian pills and equal volume of normal saline, respectively twice daily for 1 week. At 1 hour after final gavage, rats were decapitated to prepare drug sera used for culturing osteoblast-like cells. At 24, 48 and 72 hours of culture, the cellular morphology was observed, as well as the cell proliferation and alkaline phosphatase activity was detected by MTT assay and alkaline phosphatase staining, respectively. RESULTS AND CONCLUSION: Compared with the normal saline group, the cell density began to increase significantly in three Jianbuhuqian groups at 24 hours after culture, mitotic figures were easy to be observed, cells were in overlapping growth, much secretions and matrix accumulation appeared, especially in the high-dose group. The obsorbance values in Jianbuhuqian groups were significantly higher than that in the normal saline group. After 24 hours of culture, the obsorbance values in the medium-dose and high-dose groups were significantly increased compared with the low-dose group, and the values showed significant differences among three Jianbuhuqian groups after 48 and 72-hour culture. In addition, the alkaline phosphatase activity presented overt increase in the Jianbuhuqian groups compared with the normal saline group, and significant differences could be found among Jianbuhuqian groups. To conclude, the drug serum of Jianbuhuqian pills can promote the activity of osteoblast-like cells in a time- and concentration-dependent manner. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Huangqin decoction regulates autophagy to intervene with intestinal acute graft-versus-host disease in mice北大核心

BACKGROUND: How to use traditional Chinese medicine to intervene the imbalance of autophagy after intestinal mucosal barrier injury, so as to ultimately intervene the occurrence of gastrointestinal acute graft-versus-host disease, is an urgent problem to be solved after hematopoietic stem cell transplantation. OBJECTIVE: To verify the precise mechanism by which Huangqin Decoction interferes with acute intestinal graft-versus-host disease. METHODS: CB6F1 mice were randomly divided into normal control group, model control group, low-dose Huangqin Decoction group, medium-does Huangqin Decoction group and high-does Huangqin Decoction group, with 16 mice per group. CB6F1 mice in the model control group, low-dose Huangqin Decoction group, medium-does Huangqin Decoction group and high-does Huangqin Decoction group were infused with mononuclear cell suspension (bone marrow cell 8×107 + spleen cell 8×107) obtained from Balb/c mice via caudal vein within 4 hours after60Co whole body irradiation (radiation dose was 8 Gy). Different concentrations of Huangqin Decoction were given by gavage on the same day after modeling. The rats in the model control group and the normal control group were given the same volume of normal saline by gavage for 15 days. Eight hours after the last gavage, the small intestine tissues of six mice in each group were collected. PCR and western blot assay were used to detect the expression levels of LC3II/I, Beclin1 and P62. The pathological grading of small intestinal mucosa was scored by hematoxylin-eosin staining. The autophagic vesicle structure of small intestinal mucosal epithelial cells was observed by transmission electron microscope. The remaining 10 rats in each group (except the normal control group) were used to observe the clinical grading of acute graft-versus-host disease and record the survival time. RESULTS AND CONCLUSION: (1) After the application of Huangqin Decoction, the survival time of mice was significantly prolonged; the clinical acute graft-versus-host disease score was significantly decreased, and the pathological grading score of small intestinal mucosa was significantly decreased. The score of medium-does Huangqin Decoction group and high-does Huangqin Decoction group was significantly lower than that of model control group, but there was no significant difference between medium-does Huangqin Decoction group and high-does Huangqin Decoction group. (2) The LC3II/I and Beclin1 expression was significantly lower in the model control group than that in the normal control group (P < 0.01), and P62 expression was significantly higher than that in the normal control group (P < 0.01). Huangqin Decoction could promote the recovery of LC3II/I and Beclin1 levels and downregulate p62 levels (P < 0.01). (3) Under transmission electron microscope, the number of autophagic vesicles in the treatment group was significantly higher than that in the model control group, accompanied by the recovery of important organelles such as mitochondria. (4) The results confirm that by interfering autophagy related proteins, Huangqin Decoction can promote the recovery of autophagy in acute graft-versus-host disease, protect intestinal mucosal barrier and reduce intestinal rejection after transplantation and has promise as a new treatment for acute graft-versus-host disease. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

骨髓基质干细胞移植阿尔茨海默病模型大鼠：改善学习及记忆能力

BACKGROUND: Drug therapy can partly reduce and delay the progress of Alzheimer’s disease, but only 30% with the single drug treatment obtain clinical cure. OBJECTIVE: To study the therapeutic effect of bone marrow mesenchymal stem cells transplantation for rats with Alzheimer’s disease. METHODS: Amyloid β-protein was injected into the hippocampus of Sprague-Dawley rats to construct the model of Alzheimer’s disease. And bone marrow stromal stem cells were transplanted into the hippocampus of the rat models. RESULTS AND CONCLUSION: At 2 weeks after modeling, compared with the control group, the escape latency in the model and experimental groups was significantly longer (P < 0.05), which indicating that Alzheimer’s disease models were successfully established. At 4 weeks after cell transplantation, compared with the model group, the average escape latency in the experimental group was significantly decreased, but retention time on the platform quadrant was significantly prolonged (P < 0.05). Besides, at 4 weeks after cell transplantation, expression of choline acetyltransferase in the experimental group was significantly higher than that in the model group (P < 0.05). In conclusion, bone marrow mesenchymal stem cells cannot only differentiate and survive in the hippocampus of rats with Alzheimer’s disease, but also improve the learning and memory ability. 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

针灸对脑性瘫痪幼鼠模型行为学的影响及其机制

BACKGROUND: Acupuncture of “Xingnao Kaiqiao” can treat cerebral palsy by increasing cerebral blood flow, decreasing inflammatory reaction and promoting cerebral nerve repair. OBJECTIVE:To explore the influence of acupuncture of “Xingnao Kaiqiao” on behavior of immature rats with cerebral palsy and the underlying mechanism. METHODS: (1) The immature rat model of cerebral palsy was established and then randomized into control, model and acupuncture groups. (2) The immature rats in the acupuncture group were treated with acupuncture at major points of Neiguan (P 6), Renzhong (Du 26) and Sanyinjiao (Sp 6), as well as auxiliary points of Jiquan (H 1), Chize (Lu 5) and Weizhong (UB 40), while the model and control groups received no intervention. (3) Twenty-four days later, the body mass and the time removing the mackintosh at forepassed center were measured and recorded, the spatial learning and memory ability was detected by Mortis water maze test, and the serum levels of tumor necrosis factor alpha and interleukin-6 were detected by ELISA. RESULTS AND CONCLUSION: (1) The order of the body mass gained was as follows: control group > acupuncture group > model group (P < 0.05). (2) The time removing the mackintosh at forepassed center was the longest in the model group, followed by the acupuncture group, and shortest in the control group (P < 0.05). (3) Acupuncture method significantly improved the cognitive ability of immature rats, and reduced the latency of searching for platform and swimming distance compared with the model group (P < 0.05). (4) The serum levels of tumor necrosis factor alpha and interleukin-6 in the acupuncture group were significantly lower than those in the model group (P < 0.05). (5) In conclusion, the acupuncture of “Xingnao Kaiqiao” can improve the symptoms and cognitive ability of the immature rat model of cerebral palsy by up-regulating the serum levels of tumor necrosis factor alpha and interleukin-6. 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程     

Morroniside improves the neurological function in intracerebral hemorrhage rats by inhibiting inflammatory response北大核心

BACKGROUND: Morroniside has been shown to play roles of anti-inflammation, antioxidant, anti-apoptosis, promoting vascular and neural regeneration, anti-platelet aggregation and neuroprotection in the rat model of ischemic brain injury, but whether it can inhibit the inflammatory reaction of cerebral hemorrhage is unclear. OBJECTIVE: To observe the changes of inflammatory factors (interleukin-1, tumor necrosis factor-α) and inflammatory-related proteins (nuclear factor-κB and SUMO2/3) as well as neurologic function in a rat model of cerebral hemorrhage treated with morroniside at different doses. METHODS: Healthy male Sprague-Dawley rats were randomly divided into sham operation, cerebral hemorrhage and low-, medium-and high-dose morroniside groups. The model of cerebral hemorrhage was established in the latter four groups by injecting autologous blood from the tail artery, followed by intragastric injection of 30, 90, 270 mg/kg morroniside in the three morronicide groups, respectively, three times daily for consecutive 7 days; the rats in the sham operation and model groups were given same volume of normal saline. Then, the neurological function was evaluated by Neurological Severity Scores; the brain tissue around the hematoma were removed to observe the morphological changes of neurocytes around the hematoma by hematoxylin-eosin staining; the expression levels of interleukin-1 and tumor necrosis factor α in the brain tissue were detected by ELISA; the expression levels of nuclear factor-κB and SUMO2/3 were detected by immunohistochemistry and western blot assay. RESULTS AND CONCLUSION: Compared with the icerebral hemorrhage group, the low-, medium-and high-dose morroniside groups showed a significnat neurological improvement, especially the high-dose group (P < 0.05). Compared with the sham operation group, the cerebral hemorrhage and morroniside groups exhibited a significant increase in the nerve function damage and expression levels of interleukin-1, tumor necrosis factor α, nuclear factor-κB and SUMO2/3 (P < 0.05). Compared with the cerebral hemorrhage group, in the low-, medium-and high-dose morroniside groups, the expression levels of interleukin-1 and tumor necrosis factor α were significantly reduced, and expression levels of nuclear factor-κB and SUMO2/3 were significantly increased (P < 0.05). In summary, high-dose morroniside can improve the neurological function in rats with cerebral hemorrhage by down-regulating the levels of inflammatory cytokines. © 2018, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

异氟醚抑制海马神经干细胞增殖并可促其向神经元分化

BACKGROUND: Isoflurane cannot only induce a wide range of large neuronal apoptosis, but also inhibit hippocampal neurogenesis in neonatal rats, thereby resulting in hippocampus-dependent learning and memory defects.OBJECTIVE: To investigate the isoflurane effect on proliferation and differentiation of the hippocampal neural stem cells.METHODS: Twenty-six Sprague-Dawley rats were randomly divided into air group and isoflurane group (n=13 per group). Rats in the isoflurane group were subjected to 2.5% isoflurane inhalation for 3 minutes followed by 1.5% isoflurane inhalation for 4 hours. Rats in the air group only breathed in air. After the intervention, blood glucose and arterial blood gas changes were detected in the two groups. Additionally, rats in the two groups were given intraperitoneal injection of 5-bromodeoxyuridine before and after intervention. At 24 hours after the last injection of 5-bromodeoxyuridine, brain tissues were taken to make frozen sections for immunofluorescence staining.RESULTS AND CONCLUSION: There were no significant difference in pH, PaO₂, PaCO₂, HCO₃, BE and SaO₂ levels between the two groups (P > 0.05). Compared with the air group, the number of BrdU⁺ cells was significantly less in the isoflurane group (P < 0.05), while the number of NeuroD⁺/BrdU⁺ cells was significantly higher in the isoflurane group (P < 0.05). The incidence of adverse reactions was 23% in the isoflurane group, which was significantly higher than that in the air group (7.7%; P < 0.05). These findings indicate that isoflurane can inhibit the proliferation of neural stem cells in the hippocampal dentate gyrus, and promote their differentiation into neurons.    中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

Memantine combined with environmental enrichment improves spatial memory and alleviates Alzheimer’s disease-like pathology in senescence-accelerated prone-8(SAMP8) mice

Memantine is a N-methyl-D-aspartate(NMDA) receptor antagonist approved for the treatment of moderate to severe Alzheimer’s disease(AD).Environmental enrichment(EE) has shown significant beneficial effects on functional improvement in AD.In this study,we sought to determine whether combining these two distinct therapies would yield greater benefit than either drug used alone.We investigated the effect of memantine combined with EE on spatial learning and memory and AD-like pathology in a widely used AD model,the senescence-accelerated prone mice(SAMP8).The SAMP8 mice were randomly assigned to enriched housing(EH) or standard housing(SH),where either memantine(20 mg/kg) or saline was given by gastric lavage once daily continuously for eight weeks.Our results showed that,when provided separately,memantine and EE significantly improved spatial learning and memory by shortening escape latencies and increasing the frequency of entrance into the target quadrant.When combined,memantine and EE showed additive effect on learning and memory as evidenced by significant shorter escape latencies and higher frequency of target entrance than either drug alone.Consistent with the behavior results,pathological studies showed that both memantine and EE significantly reduced hippocampal CA1 neurofibrilliary tangles(NFTs) as well as amyloid beta precursor protein(APP) levels.Combining both therapies synergistically lessened NFTs and APP expression compared to either drug alone in SAMP8 mice,indicating that the combination of memantine with EE could offer a novel and efficient therapeutic strategy for the treatment of AD.     

生长激素和胰岛素样生长因子1在Lewis侏儒模型大鼠颞叶皮质中的表达

BACKGROUND:Insulin-like growth factor-1(IGF-1), a main active factor in growth hormone (GH), plays various biological functions, such as improving cognitive ability and anti-apoptotic action. OBJECTIVE:To detect the expressions of GH and IGF-1 in the temporal cortex of Lewis dwarf rats, and to explore the effect of different concentrations of GH on the differentiation of hippocampal nerve stem cells (NSCs). METHODS:Lewis dwarf rats aged 11(adult) and 20 (senile) month olds and normal wild-type rats were euthanized by decapitation, underwent the craniotomy quickly, and the temporal cortex in the cold saline was extracted. GH and IGF-1 levels were detected using western blotting. After isolation, purification and identification of the rat hippocampal NSCs, the effect of GH in different concentrations (10, 30, 90 μg/L) on the NSCs differentiation was determined at 96 hours after culture. RESULTS AND CONCLUSION:The GH level in the temporal cortex did not differ significantly among rats (P > 0.05). While the IGF-I level in the temporal cortex of Lewis dwarf rats was significantly higher than that of the wild-type rats (P < 0.05). The GH level in the temporal cortex of adult female Lewis dwarf rats was significantly lower than that of the male rats (P < 0.05). Immunofluorescence showed that the proportion of β III-tubulin-positive neurons was significantly higher than that in the control group (P < 0.05) after the hippocampal NSCs and precursor cells cultured for 96 hours with GH (30 μg/L), but there was no significant difference between the control group and treatment group with GH of 10 or 90 μg/L. These results suggest that GH and IGF-I are expressed in the temporal cortex of both Lewis dwarf and wild-type rats which are independent from pituitary GH and the peripheral circulating IGF-1. Additionally, GH can promote the differentiation of hippocampal NSCs and precursor cells into neurons. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.